The development of the reproductive systems begins soon after fertilization of the egg, with primordial gonads beginning to develop approximately one month after conception. Reproductive development continues in utero, but there is little change in the reproductive system between infancy and puberty.
Development of the Sexual Organs in the Embryo and Fetus
Females are considered the “fundamental” sex—that is, without much chemical prompting, all fertilized eggs would develop into females. To become a male, an individual must be exposed to the cascade of factors initiated by a single gene on the male Y chromosome. This is called the SRY (Sex-determining Region of the Y chromosome). Because females do not have a Y chromosome, they do not have the SRY gene. Without a functional SRY gene, an individual will be female.
In both male and female embryos, the same group of cells has the potential to develop into either the male or female gonads; this tissue is considered bipotential. The SRY gene actively recruits other genes that begin to develop the testes, and suppresses genes that are important in female development. As part of this SRY-prompted cascade, germ cells in the bipotential gonads differentiate into spermatogonia. Without SRY, different genes are expressed, oogonia form, and primordial follicles develop in the primitive ovary.
Soon after the formation of the testis, the Leydig cells begin to secrete testosterone. Testosterone can influence tissues that are bipotential to become male reproductive structures. For example, with exposure to testosterone, cells that could become either the glans penis or the glans clitoris form the glans penis. Without testosterone, these same cells differentiate into the clitoris.
Not all tissues in the reproductive tract are bipotential. The internal reproductive structures (for example the uterus, uterine tubes, and part of the vagina in females; and the epididymis, ductus deferens, and seminal vesicles in males) form from one of two rudimentary duct systems in the embryo. For proper reproductive function in the adult, one set of these ducts must develop properly, and the other must degrade. In males, secretions from sustentacular cells trigger a degradation of the female duct, called the Müllerian duct. At the same time, testosterone secretion stimulates growth of the male tract, the Wolffian duct. Without such sustentacular cell secretion, the Müllerian duct will develop; without testosterone, the Wolffian duct will degrade. Thus, the developing offspring will be female. For more information and a figure of differentiation of the gonads, seek additional content on fetal development.
Further Sexual Development Occurs at Puberty
Puberty is the stage of development at which individuals become sexually mature. Though the outcomes of puberty for boys and girls are very different, the hormonal control of the process is very similar. In addition, though the timing of these events varies between individuals, the sequence of changes that occur is predictable for male and female adolescents. As shown in Figure 27.18, a concerted release of hormones from the hypothalamus (GnRH), the anterior pituitary (LH and FSH), and the gonads (either testosterone or estrogen) is responsible for the maturation of the reproductive systems and the development of secondary sex characteristics, which are physical changes that serve auxiliary roles in reproduction.
The first changes begin around the age of eight or nine when the production of LH becomes detectable. The release of LH occurs primarily at night during sleep and precedes the physical changes of puberty by several years. In pre-pubertal children, the sensitivity of the negative feedback system in the hypothalamus and pituitary is very high. This means that very low concentrations of androgens or estrogens will negatively feed back onto the hypothalamus and pituitary, keeping the production of GnRH, LH, and FSH low.
As an individual approaches puberty, two changes in sensitivity occur. The first is a decrease of sensitivity in the hypothalamus and pituitary to negative feedback, meaning that it takes increasingly larger concentrations of sex steroid hormones to stop the production of LH and FSH. The second change in sensitivity is an increase in sensitivity of the gonads to the FSH and LH signals, meaning the gonads of adults are more responsive to gonadotropins than are the gonads of children. As a result of these two changes, the levels of LH and FSH slowly increase and lead to the enlargement and maturation of the gonads, which in turn leads to secretion of higher levels of sex hormones and the initiation of spermatogenesis and folliculogenesis.
In addition to age, multiple factors can affect the age of onset of puberty, including genetics, environment, and psychological stress. One of the more important influences may be nutrition; historical data demonstrate the effect of better and more consistent nutrition on the age of menarche in girls in the United States, which decreased from an average age of approximately 17 years of age in 1860 to the current age of approximately 12.75 years in 1960, as it remains today. Some studies indicate a link between puberty onset and the amount of stored fat in an individual. This effect is more pronounced in girls, but has been documented in both sexes. Body fat, corresponding with secretion of the hormone leptin by adipose cells, appears to have a strong role in determining menarche. This may reflect to some extent the high metabolic costs of gestation and lactation. In girls who are lean and highly active, such as gymnasts, there is often a delay in the onset of puberty.
Figure 27.18 Hormones of Puberty During puberty, the release of LH and FSH from the anterior pituitary stimulates the gonads to produce sex hormones in both male and female adolescents.
Signs of Puberty
Different sex steroid hormone concentrations between the sexes also contribute to the development and function of secondary sexual characteristics. Examples of secondary sexual characteristics are listed in Table 27.1.Development of the Secondary Sexual Characteristics
Increased larynx size and deepening of the voice
Deposition of fat, predominantly in breasts and hips
Increased muscular development
Growth of facial, axillary, and pubic hair, and increased growth of body hair
Broadening of the pelvis and growth of axillary and pubic hair
As a girl reaches puberty, typically the first change that is visible is the development of the breast tissue. This is followed by the growth of axillary and pubic hair. A growth spurt normally starts at approximately age 9 to 11, and may last two years or more. During this time, a girl’s height can increase 3 inches a year. The next step in puberty is menarche, the start of menstruation.
In boys, the growth of the testes is typically the first physical sign of the beginning of puberty, which is followed by growth and pigmentation of the scrotum and growth of the penis. The next step is the growth of hair, including armpit, pubic, chest, and facial hair. Testosterone stimulates the growth of the larynx and thickening and lengthening of the vocal folds, which causes the voice to drop in pitch. The first fertile ejaculations typically appear at approximately 15 years of age, but this age can vary widely across individual boys. Unlike the early growth spurt observed in females, the male growth spurt occurs toward the end of puberty, at approximately age 11 to 13, and a boy’s height can increase as much as 4 inches a year. In some males, pubertal development can continue through the early 20s.
The female reproductive system functions to produce gametes and reproductive hormones, just like the male reproductive system; however, it also has the additional task of supporting the developing fetus and delivering it to the outside world. Unlike its male counterpart, the female reproductive system is located primarily inside the pelvic cavity (Figure 27.9). Recall that the ovaries are the female gonads. The gamete they produce is called an oocyte. We’ll discuss the production of oocytes in detail shortly. First, let’s look at some of the structures of the female reproductive system.
Figure 27.9 Female Reproductive System The major organs of the female reproductive system are located inside the pelvic cavity.
External Female Genitals
The external female reproductive structures are referred to collectively as the vulva (Figure 27.10). The mons pubis is a pad of fat that is located at the anterior, over the pubic bone. After puberty, it becomes covered in pubic hair. The labia majora (labia = “lips”; majora = “larger”) are folds of hair-covered skin that begin just posterior to the mons pubis. The thinner and more pigmented labia minora (labia = “lips”; minora = “smaller”) extend medial to the labia majora. Although they naturally vary in shape and size from woman to woman, the labia minora serve to protect the female urethra and the entrance to the female reproductive tract.
The superior, anterior portions of the labia minora come together to encircle the clitoris (or glans clitoris), an organ that originates from the same cells as the glans penis and has abundant nerves that make it important in sexual sensation and orgasm. The hymen is a thin membrane that sometimes partially covers the entrance to the vagina. An intact hymen cannot be used as an indication of “virginity”; even at birth, this is only a partial membrane, as menstrual fluid and other secretions must be able to exit the body, regardless of penile–vaginal intercourse. The vaginal opening is located between the opening of the urethra and the anus. It is flanked by outlets to the Bartholin’s glands (or greater vestibular glands).
Figure 27.10 The Vulva The external female genitalia are referred to collectively as the vulva.
The vagina, shown at the bottom of Figure 27.9 and Figure 27.10, is a muscular canal (approximately 10 cm long) that serves as the entrance to the reproductive tract. It also serves as the exit from the uterus during menses and childbirth. The outer walls of the anterior and posterior vagina are formed into longitudinal columns, or ridges, and the superior portion of the vagina—called the fornix—meets the protruding uterine cervix. The walls of the vagina are lined with an outer, fibrous adventitia; a middle layer of smooth muscle; and an inner mucous membrane with transverse folds called rugae. Together, the middle and inner layers allow the expansion of the vagina to accommodate intercourse and childbirth. The thin, perforated hymen can partially surround the opening to the vaginal orifice. The hymen can be ruptured with strenuous physical exercise, penile–vaginal intercourse, and childbirth. The Bartholin’s glands and the lesser vestibular glands (located near the clitoris) secrete mucus, which keeps the vestibular area moist.
The vagina is home to a normal population of microorganisms that help to protect against infection by pathogenic bacteria, yeast, or other organisms that can enter the vagina. In a healthy woman, the most predominant type of vaginal bacteria is from the genus Lactobacillus. This family of beneficial bacterial flora secretes lactic acid, and thus protects the vagina by maintaining an acidic pH (below 4.5). Potential pathogens are less likely to survive in these acidic conditions. Lactic acid, in combination with other vaginal secretions, makes the vagina a self-cleansing organ. However, douching—or washing out the vagina with fluid—can disrupt the normal balance of healthy microorganisms, and actually increase a woman’s risk for infections and irritation. Indeed, the American College of Obstetricians and Gynecologists recommend that women do not douche, and that they allow the vagina to maintain its normal healthy population of protective microbial flora.
The ovaries are the female gonads (see Figure 27.9). Paired ovals, they are each about 2 to 3 cm in length, about the size of an almond. The ovaries are located within the pelvic cavity, and are supported by the mesovarium, an extension of the peritoneum that connects the ovaries to the broad ligament. Extending from the mesovarium itself is the suspensory ligament that contains the ovarian blood and lymph vessels. Finally, the ovary itself is attached to the uterus via the ovarian ligament.
The ovary comprises an outer covering of cuboidal epithelium called the ovarian surface epithelium that is superficial to a dense connective tissue covering called the tunica albuginea. Beneath the tunica albuginea is the cortex, or outer portion, of the organ. The cortex is composed of a tissue framework called the ovarian stroma that forms the bulk of the adult ovary. Oocytes develop within the outer layer of this stroma, each surrounded by supporting cells. This grouping of an oocyte and its supporting cells is called a follicle. The growth and development of ovarian follicles will be described shortly. Beneath the cortex lies the inner ovarian medulla, the site of blood vessels, lymph vessels, and the nerves of the ovary. You will learn more about the overall anatomy of the female reproductive system at the end of this section.
The Ovarian Cycle
The ovarian cycle is a set of predictable changes in a female’s oocytes and ovarian follicles. During a woman’s reproductive years, it is a roughly 28-day cycle that can be correlated with, but is not the same as, the menstrual cycle (discussed shortly). The cycle includes two interrelated processes: oogenesis (the production of female gametes) and folliculogenesis (the growth and development of ovarian follicles).
Gametogenesis in females is called oogenesis. The process begins with the ovarian stem cells, or oogonia (Figure 27.11). Oogonia are formed during fetal development, and divide via mitosis, much like spermatogonia in the testis. Unlike spermatogonia, however, oogonia form primary oocytes in the fetal ovary prior to birth. These primary oocytes are then arrested in this stage of meiosis I, only to resume it years later, beginning at puberty and continuing until the woman is near menopause (the cessation of a woman’s reproductive functions). The number of primary oocytes present in the ovaries declines from one to two million in an infant, to approximately 400,000 at puberty, to zero by the end of menopause.
The initiation of ovulation—the release of an oocyte from the ovary—marks the transition from puberty into reproductive maturity for women. From then on, throughout a woman’s reproductive years, ovulation occurs approximately once every 28 days. Just prior to ovulation, a surge of luteinizing hormone triggers the resumption of meiosis in a primary oocyte. This initiates the transition from primary to secondary oocyte. However, as you can see in Figure 27.11, this cell division does not result in two identical cells. Instead, the cytoplasm is divided unequally, and one daughter cell is much larger than the other. This larger cell, the secondary oocyte, eventually leaves the ovary during ovulation. The smaller cell, called the first polar body, may or may not complete meiosis and produce second polar bodies; in either case, it eventually disintegrates. Therefore, even though oogenesis produces up to four cells, only one survives.
Figure 27.11 Oogenesis The unequal cell division of oogenesis produces one to three polar bodies that later degrade, as well as a single haploid ovum, which is produced only if there is penetration of the secondary oocyte by a sperm cell.
How does the diploid secondary oocyte become an ovum—the haploid female gamete? Meiosis of a secondary oocyte is completed only if a sperm succeeds in penetrating its barriers. Meiosis II then resumes, producing one haploid ovum that, at the instant of fertilization by a (haploid) sperm, becomes the first diploid cell of the new offspring (a zygote). Thus, the ovum can be thought of as a brief, transitional, haploid stage between the diploid oocyte and diploid zygote.
The larger amount of cytoplasm contained in the female gamete is used to supply the developing zygote with nutrients during the period between fertilization and implantation into the uterus. Interestingly, sperm contribute only DNA at fertilization —not cytoplasm. Therefore, the cytoplasm and all of the cytoplasmic organelles in the developing embryo are of maternal origin. This includes mitochondria, which contain their own DNA. Scientific research in the 1980s determined that mitochondrial DNA was maternally inherited, meaning that you can trace your mitochondrial DNA directly to your mother, her mother, and so on back through your female ancestors.
Again, ovarian follicles are oocytes and their supporting cells. They grow and develop in a process called folliculogenesis, which typically leads to ovulation of one follicle approximately every 28 days, along with death to multiple other follicles. The death of ovarian follicles is called atresia, and can occur at any point during follicular development. Recall that, a female infant at birth will have one to two million oocytes within her ovarian follicles, and that this number declines throughout life until menopause, when no follicles remain. As you’ll see next, follicles progress from primordial, to primary, to secondary and tertiary stages prior to ovulation—with the oocyte inside the follicle remaining as a primary oocyte until right before ovulation.
Folliculogenesis begins with follicles in a resting state. These small primordial follicles are present in newborn females and are the prevailing follicle type in the adult ovary (Figure 27.12). Primordial follicles have only a single flat layer of support cells, called granulosa cells, that surround the oocyte, and they can stay in this resting state for years—some until right before menopause.
After puberty, a few primordial follicles will respond to a recruitment signal each day, and will join a pool of immature growing follicles called primary follicles. Primary follicles start with a single layer of granulosa cells, but the granulosa cells then become active and transition from a flat or squamous shape to a rounded, cuboidal shape as they increase in size and proliferate. As the granulosa cells divide, the follicles—now called secondary follicles (see Figure 27.12)—increase in diameter, adding a new outer layer of connective tissue, blood vessels, and theca cells—cells that work with the granulosa cells to produce estrogens.
Within the growing secondary follicle, the primary oocyte now secretes a thin acellular membrane called the zona pellucida that will play a critical role in fertilization. A thick fluid, called follicular fluid, that has formed between the granulosa cells also begins to collect into one large pool, or antrum. Follicles in which the antrum has become large and fully formed are considered tertiary follicles (or antral follicles). Several follicles reach the tertiary stage at the same time, and most of these will undergo atresia. The one that does not die will continue to grow and develop until ovulation, when it will expel its secondary oocyte surrounded by several layers of granulosa cells from the ovary. Keep in mind that most follicles don’t make it to this point. In fact, roughly 99 percent of the follicles in the ovary will undergo atresia, which can occur at any stage of folliculogenesis.
Figure 27.12 Folliculogenesis (a) The maturation of a follicle is shown in a clockwise direction proceeding from the primordial follicles. FSH stimulates the growth of a tertiary follicle, and LH stimulates the production of estrogen by granulosa and theca cells. Once the follicle is mature, it ruptures and releases the oocyte. Cells remaining in the follicle then develop into the corpus luteum. (b) In this electron micrograph of a secondary follicle, the oocyte, theca cells (thecae folliculi), and developing antrum are clearly visible.
Hormonal Control of the Ovarian Cycle
The process of development that we have just described, from primordial follicle to early tertiary follicle, takes approximately two months in humans. The final stages of development of a small cohort of tertiary follicles, ending with ovulation of a secondary oocyte, occur over a course of approximately 28 days. These changes are regulated by many of the same hormones that regulate the male reproductive system, including GnRH, LH, and FSH.
As in men, the hypothalamus produces GnRH, a hormone that signals the anterior pituitary gland to produce the gonadotropins FSH and LH (Figure 27.13). These gonadotropins leave the pituitary and travel through the bloodstream to the ovaries, where they bind to receptors on the granulosa and theca cells of the follicles. FSH stimulates the follicles to grow (hence its name of follicle-stimulating hormone), and the five or six tertiary follicles expand in diameter. The release of LH also stimulates the granulosa and theca cells of the follicles to produce the sex steroid hormone estradiol, a type of estrogen. This phase of the ovarian cycle, when the tertiary follicles are growing and secreting estrogen, is known as the follicular phase.
The more granulosa and theca cells a follicle has (that is, the larger and more developed it is), the more estrogen it will produce in response to LH stimulation. As a result of these large follicles producing large amounts of estrogen, systemic plasma estrogen concentrations increase. Following a classic negative feedback loop, the high concentrations of estrogen will stimulate the hypothalamus and pituitary to reduce the production of GnRH, LH, and FSH. Because the large tertiary follicles require FSH to grow and survive at this point, this decline in FSH caused by negative feedback leads most of them to die (atresia). Typically only one follicle, now called the dominant follicle, will survive this reduction in FSH, and this follicle will be the one that releases an oocyte. Scientists have studied many factors that lead to a particular follicle becoming dominant: size, the number of granulosa cells, and the number of FSH receptors on those granulosa cells all contribute to a follicle becoming the one surviving dominant follicle.
Figure 27.13 Hormonal Regulation of Ovulation The hypothalamus and pituitary gland regulate the ovarian cycle and ovulation. GnRH activates the anterior pituitary to produce LH and FSH, which stimulate the production of estrogen and progesterone by the ovaries.
When only the one dominant follicle remains in the ovary, it again begins to secrete estrogen. It produces more estrogen than all of the developing follicles did together before the negative feedback occurred. It produces so much estrogen that the normal negative feedback doesn’t occur. Instead, these extremely high concentrations of systemic plasma estrogen trigger a regulatory switch in the anterior pituitary that responds by secreting large amounts of LH and FSH into the bloodstream (see Figure 27.13). The positive feedback loop by which more estrogen triggers release of more LH and FSH only occurs at this point in the cycle.
It is this large burst of LH (called the LH surge) that leads to ovulation of the dominant follicle. The LH surge induces many changes in the dominant follicle, including stimulating the resumption of meiosis of the primary oocyte to a secondary oocyte. As noted earlier, the polar body that results from unequal cell division simply degrades. The LH surge also triggers proteases (enzymes that cleave proteins) to break down structural proteins in the ovary wall on the surface of the bulging dominant follicle. This degradation of the wall, combined with pressure from the large, fluid-filled antrum, results in the expulsion of the oocyte surrounded by granulosa cells into the peritoneal cavity. This release is ovulation.
In the next section, you will follow the ovulated oocyte as it travels toward the uterus, but there is one more important event that occurs in the ovarian cycle. The surge of LH also stimulates a change in the granulosa and theca cells that remain in the follicle after the oocyte has been ovulated. This change is called luteinization (recall that the full name of LH is luteinizing hormone), and it transforms the collapsed follicle into a new endocrine structure called the corpus luteum, a term meaning “yellowish body” (see Figure 27.12). Instead of estrogen, the luteinized granulosa and theca cells of the corpus luteum begin to produce large amounts of the sex steroid hormone progesterone, a hormone that is critical for the establishment and maintenance of pregnancy. Progesterone triggers negative feedback at the hypothalamus and pituitary, which keeps GnRH, LH, and FSH secretions low, so no new dominant follicles develop at this time.
The post-ovulatory phase of progesterone secretion is known as the luteal phase of the ovarian cycle. If pregnancy does not occur within 10 to 12 days, the corpus luteum will stop secreting progesterone and degrade into the corpus albicans, a nonfunctional “whitish body” that will disintegrate in the ovary over a period of several months. During this time of reduced progesterone secretion, FSH and LH are once again stimulated, and the follicular phase begins again with a new cohort of early tertiary follicles beginning to grow and secrete estrogen.
The Uterine Tubes
The uterine tubes (also called fallopian tubes or oviducts) serve as the conduit of the oocyte from the ovary to the uterus (Figure 27.14). Each of the two uterine tubes is close to, but not directly connected to, the ovary and divided into sections. The isthmus is the narrow medial end of each uterine tube that is connected to the uterus. The wide distal infundibulum flares out with slender, finger-like projections called fimbriae. The middle region of the tube, called the ampulla, is where fertilization often occurs. The uterine tubes also have three layers: an outer serosa, a middle smooth muscle layer, and an inner mucosal layer. In addition to its mucus-secreting cells, the inner mucosa contains ciliated cells that beat in the direction of the uterus, producing a current that will be critical to move the oocyte.
Following ovulation, the secondary oocyte surrounded by a few granulosa cells is released into the peritoneal cavity. The nearby uterine tube, either left or right, receives the oocyte. Unlike sperm, oocytes lack flagella, and therefore cannot move on their own. So how do they travel into the uterine tube and toward the uterus? High concentrations of estrogen that occur around the time of ovulation induce contractions of the smooth muscle along the length of the uterine tube. These contractions occur every 4 to 8 seconds, and the result is a coordinated movement that sweeps the surface of the ovary and the pelvic cavity. Current flowing toward the uterus is generated by coordinated beating of the cilia that line the outside and lumen of the length of the uterine tube. These cilia beat more strongly in response to the high estrogen concentrations that occur around the time of ovulation. As a result of these mechanisms, the oocyte–granulosa cell complex is pulled into the interior of the tube. Once inside, the muscular contractions and beating cilia move the oocyte slowly toward the uterus. When fertilization does occur, sperm typically meet the egg while it is still moving through the ampulla.
If the oocyte is successfully fertilized, the resulting zygote will begin to divide into two cells, then four, and so on, as it makes its way through the uterine tube and into the uterus. There, it will implant and continue to grow. If the egg is not fertilized, it will simply degrade—either in the uterine tube or in the uterus, where it may be shed with the next menstrual period.
Figure 27.14 Ovaries, Uterine Tubes, and Uterus This anterior view shows the relationship of the ovaries, uterine tubes (oviducts), and uterus. Sperm enter through the vagina, and fertilization of an ovulated oocyte usually occurs in the distal uterine tube. From left to right,
The open-ended structure of the uterine tubes can have significant health consequences if bacteria or other contagions enter through the vagina and move through the uterus, into the tubes, and then into the pelvic cavity. If this is left unchecked, a bacterial infection (sepsis) could quickly become life-threatening. The spread of an infection in this manner is of special concern when unskilled practitioners perform abortions in non-sterile conditions. Sepsis is also associated with sexually transmitted bacterial infections, especially gonorrhea and chlamydia. These increase a woman’s risk for pelvic inflammatory disease (PID), infection of the uterine tubes or other reproductive organs. Even when resolved, PID can leave scar tissue in the tubes, leading to infertility.
The Uterus and Cervix
The uterus is the muscular organ that nourishes and supports the growing embryo (see Figure 27.14). Its average size is approximately 5 cm wide by 7 cm long (approximately 2 in by 3 in) when a female is not pregnant. It has three sections. The portion of the uterus superior to the opening of the uterine tubes is called the fundus. The middle section of the uterus is called the body of uterus (or corpus). The cervix is the narrow inferior portion of the uterus that projects into the vagina. The cervix produces mucus secretions that become thin and stringy under the influence of high systemic plasma estrogen concentrations, and these secretions can facilitate sperm movement through the reproductive tract.
Several ligaments maintain the position of the uterus within the abdominopelvic cavity. The broad ligament is a fold of peritoneum that serves as a primary support for the uterus, extending laterally from both sides of the uterus and attaching it to the pelvic wall. The round ligament attaches to the uterus near the uterine tubes, and extends to the labia majora. Finally, the uterosacral ligament stabilizes the uterus posteriorly by its connection from the cervix to the pelvic wall.
The wall of the uterus is made up of three layers. The most superficial layer is the serous membrane, or perimetrium, which consists of epithelial tissue that covers the exterior portion of the uterus. The middle layer, or myometrium, is a thick layer of smooth muscle responsible for uterine contractions. Most of the uterus is myometrial tissue, and the muscle fibers run horizontally, vertically, and diagonally, allowing the powerful contractions that occur during labor and the less powerful contractions (or cramps) that help to expel menstrual blood during a woman’s period. Anteriorly directed myometrial contractions also occur near the time of ovulation, and are thought to possibly facilitate the transport of sperm through the female reproductive tract.
The innermost layer of the uterus is called the endometrium. The endometrium contains a connective tissue lining, the lamina propria, which is covered by epithelial tissue that lines the lumen. Structurally, the endometrium consists of two layers: the stratum basalis and the stratum functionalis (the basal and functional layers). The stratum basalis layer is part of the lamina propria and is adjacent to the myometrium; this layer does not shed during menses. In contrast, the thicker stratum functionalis layer contains the glandular portion of the lamina propria and the endothelial tissue that lines the uterine lumen. It is the stratum functionalis that grows and thickens in response to increased levels of estrogen and progesterone. In the luteal phase of the menstrual cycle, special branches off of the uterine artery called spiral arteries supply the thickened stratum functionalis. This inner functional layer provides the proper site of implantation for the fertilized egg, and—should fertilization not occur—it is only the stratum functionalis layer of the endometrium that sheds during menstruation.
Recall that during the follicular phase of the ovarian cycle, the tertiary follicles are growing and secreting estrogen. At the same time, the stratum functionalis of the endometrium is thickening to prepare for a potential implantation. The post-ovulatory increase in progesterone, which characterizes the luteal phase, is key for maintaining a thick stratum functionalis. As long as a functional corpus luteum is present in the ovary, the endometrial lining is prepared for implantation. Indeed, if an embryo implants, signals are sent to the corpus luteum to continue secreting progesterone to maintain the endometrium, and thus maintain the pregnancy. If an embryo does not implant, no signal is sent to the corpus luteum and it degrades, ceasing progesterone production and ending the luteal phase. Without progesterone, the endometrium thins and, under the influence of prostaglandins, the spiral arteries of the endometrium constrict and rupture, preventing oxygenated blood from reaching the endometrial tissue. As a result, endometrial tissue dies and blood, pieces of the endometrial tissue, and white blood cells are shed through the vagina during menstruation, or the menses. The first menses after puberty, called menarche, can occur either before or after the first ovulation.
The Menstrual Cycle
Now that we have discussed the maturation of the cohort of tertiary follicles in the ovary, the build-up and then shedding of the endometrial lining in the uterus, and the function of the uterine tubes and vagina, we can put everything together to talk about the three phases of the menstrual cycle—the series of changes in which the uterine lining is shed, rebuilds, and prepares for implantation.
The timing of the menstrual cycle starts with the first day of menses, referred to as day one of a woman’s period. Cycle length is determined by counting the days between the onset of bleeding in two subsequent cycles. Because the average length of a woman’s menstrual cycle is 28 days, this is the time period used to identify the timing of events in the cycle. However, the length of the menstrual cycle varies among women, and even in the same woman from one cycle to the next, typically from 21 to 32 days.
Just as the hormones produced by the granulosa and theca cells of the ovary “drive” the follicular and luteal phases of the ovarian cycle, they also control the three distinct phases of the menstrual cycle. These are the menses phase, the proliferative phase, and the secretory phase.
The menses phase of the menstrual cycle is the phase during which the lining is shed; that is, the days that the woman menstruates. Although it averages approximately five days, the menses phase can last from 2 to 7 days, or longer. As shown in Figure 27.15, the menses phase occurs during the early days of the follicular phase of the ovarian cycle, when progesterone, FSH, and LH levels are low. Recall that progesterone concentrations decline as a result of the degradation of the corpus luteum, marking the end of the luteal phase. This decline in progesterone triggers the shedding of the stratum functionalis of the endometrium.
Figure 27.15 Hormone Levels in Ovarian and Menstrual Cycles The correlation of the hormone levels and their effects on the female reproductive system is shown in this timeline of the ovarian and menstrual cycles. The menstrual cycle begins at day one with the start of menses. Ovulation occurs around day 14 of a 28-day cycle, triggered by the LH surge.
Once menstrual flow ceases, the endometrium begins to proliferate again, marking the beginning of the proliferative phase of the menstrual cycle (see Figure 27.15). It occurs when the granulosa and theca cells of the tertiary follicles begin to produce increased amounts of estrogen. These rising estrogen concentrations stimulate the endometrial lining to rebuild.
Recall that the high estrogen concentrations will eventually lead to a decrease in FSH as a result of negative feedback, resulting in atresia of all but one of the developing tertiary follicles. The switch to positive feedback—which occurs with the elevated estrogen production from the dominant follicle—then stimulates the LH surge that will trigger ovulation. In a typical 28-day menstrual cycle, ovulation occurs on day 14. Ovulation marks the end of the proliferative phase as well as the end of the follicular phase.
In addition to prompting the LH surge, high estrogen levels increase the uterine tube contractions that facilitate the pick-up and transfer of the ovulated oocyte. High estrogen levels also slightly decrease the acidity of the vagina, making it more hospitable to sperm. In the ovary, the luteinization of the granulosa cells of the collapsed follicle forms the progesterone-producing corpus luteum, marking the beginning of the luteal phase of the ovarian cycle. In the uterus, progesterone from the corpus luteum begins the secretory phase of the menstrual cycle, in which the endometrial lining prepares for implantation (see Figure 27.15). Over the next 10 to 12 days, the endometrial glands secrete a fluid rich in glycogen. If fertilization has occurred, this fluid will nourish the ball of cells now developing from the zygote. At the same time, the spiral arteries develop to provide blood to the thickened stratum functionalis.
If no pregnancy occurs within approximately 10 to 12 days, the corpus luteum will degrade into the corpus albicans. Levels of both estrogen and progesterone will fall, and the endometrium will grow thinner. Prostaglandins will be secreted that cause constriction of the spiral arteries, reducing oxygen supply. The endometrial tissue will die, resulting in menses—or the first day of the next cycle.
Whereas the breasts are located far from the other female reproductive organs, they are considered accessory organs of the female reproductive system. The function of the breasts is to supply milk to an infant in a process called lactation. The external features of the breast include a nipple surrounded by a pigmented areola (Figure 27.17), whose coloration may deepen during pregnancy. The areola is typically circular and can vary in size from 25 to 100 mm in diameter. The areolar region is characterized by small, raised areolar glands that secrete lubricating fluid during lactation to protect the nipple from chafing. When a baby nurses, or draws milk from the breast, the entire areolar region is taken into the mouth.
Breast milk is produced by the mammary glands, which are modified sweat glands. The milk itself exits the breast through the nipple via 15 to 20 lactiferous ducts that open on the surface of the nipple. These lactiferous ducts each extend to a lactiferous sinus that connects to a glandular lobe within the breast itself that contains groups of milk-secreting cells in clusters called alveoli (see Figure 27.17). The clusters can change in size depending on the amount of milk in the alveolar lumen. Once milk is made in the alveoli, stimulated myoepithelial cells that surround the alveoli contract to push the milk to the lactiferous sinuses. From here, the baby can draw milk through the lactiferous ducts by suckling. The lobes themselves are surrounded by fat tissue, which determines the size of the breast; breast size differs between individuals and does not affect the amount of milk produced. Supporting the breasts are multiple bands of connective tissue called suspensory ligaments that connect the breast tissue to the dermis of the overlying skin.
Figure 27.17 Anatomy of the Breast During lactation, milk moves from the alveoli through the lactiferous ducts to the nipple.
During the normal hormonal fluctuations in the menstrual cycle, breast tissue responds to changing levels of estrogen and progesterone, which can lead to swelling and breast tenderness in some individuals, especially during the secretory phase. If pregnancy occurs, the increase in hormones leads to further development of the mammary tissue and enlargement of the breasts.
Hormonal Birth Control
Birth control pills take advantage of the negative feedback system that regulates the ovarian and menstrual cycles to stop ovulation and prevent pregnancy. Typically they work by providing a constant level of both estrogen and progesterone, which negatively feeds back onto the hypothalamus and pituitary, thus preventing the release of FSH and LH. Without FSH, the follicles do not mature, and without the LH surge, ovulation does not occur. Although the estrogen in birth control pills does stimulate some thickening of the endometrial wall, it is reduced compared with a normal cycle and is less likely to support implantation.
Some birth control pills contain 21 active pills containing hormones, and 7 inactive pills (placebos). The decline in hormones during the week that the woman takes the placebo pills triggers menses, although it is typically lighter than a normal menstrual flow because of the reduced endometrial thickening. Newer types of birth control pills have been developed that deliver low-dose estrogens and progesterone for the entire cycle (these are meant to be taken 365 days a year), and menses never occurs. While some women prefer to have the proof of a lack of pregnancy that a monthly period provides, menstruation every 28 days is not required for health reasons, and there are no reported adverse effects of not having a menstrual period in an otherwise healthy individual.
Because birth control pills function by providing constant estrogen and progesterone levels and disrupting negative feedback, skipping even just one or two pills at certain points of the cycle (or even being several hours late taking the pill) can lead to an increase in FSH and LH and result in ovulation. It is important, therefore, that the woman follow the directions on the birth control pill package to successfully prevent pregnancy.
Unique for its role in human reproduction, a gamete is a specialized sex cell carrying 23 chromosomes—one half the number in body cells. At fertilization, the chromosomes in one male gamete, called a sperm (or spermatozoon), combine with the chromosomes in one female gamete, called an oocyte. The function of the male reproductive system (Figure 27.2) is to produce sperm and transfer them to the female reproductive tract. The paired testes are a crucial component in this process, as they produce both sperm and androgens, the hormones that support male reproductive physiology. In humans, the most important male androgen is testosterone. Several accessory organs and ducts aid the process of sperm maturation and transport the sperm and other seminal components to the penis, which delivers sperm to the female reproductive tract. In this section, we examine each of these different structures, and discuss the process of sperm production and transport.
Figure 27.2 Male Reproductive System The structures of the male reproductive system include the testes, the epididymides, the penis, and the ducts and glands that produce and carry semen. Sperm exit the scrotum through the ductus deferens, which is bundled in the spermatic cord. The seminal vesicles and prostate gland add fluids to the sperm to create semen.
The testes are located in a skin-covered, highly pigmented, muscular sack called the scrotum that extends from the body behind the penis (see Figure 27.2). This location is important in sperm production, which occurs within the testes, and proceeds more efficiently when the testes are kept 2 to 4°C below core body temperature.
The dartos muscle makes up the subcutaneous muscle layer of the scrotum (Figure 27.3). It continues internally to make up the scrotal septum, a wall that divides the scrotum into two compartments, each housing one testis. Descending from the internal oblique muscle of the abdominal wall are the two cremaster muscles, which cover each testis like a muscular net. By contracting simultaneously, the dartos and cremaster muscles can elevate the testes in cold weather (or water), moving the testes closer to the body and decreasing the surface area of the scrotum to retain heat. Alternatively, as the environmental temperature increases, the scrotum relaxes, moving the testes farther from the body core and increasing scrotal surface area, which promotes heat loss. Externally, the scrotum has a raised medial thickening on the surface called the raphae.
Figure 27.3 The Scrotum and Testes This anterior view shows the structures of the scrotum and testes.
The testes (singular = testis) are the male gonads—that is, the male reproductive organs. They produce both sperm and androgens, such as testosterone, and are active throughout the reproductive lifespan of the male.
Paired ovals, the testes are each approximately 4 to 5 cm in length and are housed within the scrotum (see Figure 27.3). They are surrounded by two distinct layers of protective connective tissue (Figure 27.4). The outer tunica vaginalis is a serous membrane that has both a parietal and a thin visceral layer. Beneath the tunica vaginalis is the tunica albuginea, a tough, white, dense connective tissue layer covering the testis itself. Not only does the tunica albuginea cover the outside of the testis, it also invaginates to form septa that divide the testis into 300 to 400 structures called lobules. Within the lobules, sperm develop in structures called seminiferous tubules. During the seventh month of the developmental period of a male fetus, each testis moves through the abdominal musculature to descend into the scrotal cavity. This is called the “descent of the testis.” Cryptorchidism is the clinical term used when one or both of the testes fail to descend into the scrotum prior to birth.
Figure 27.4 Anatomy of the Testis This sagittal view shows the seminiferous tubules, the site of sperm production. Formed sperm are transferred to the epididymis, where they mature. They leave the epididymis during an ejaculation via the ductus deferens.
The tightly coiled seminiferous tubules form the bulk of each testis. They are composed of developing sperm cells surrounding a lumen, the hollow center of the tubule, where formed sperm are released into the duct system of the testis. Specifically, from the lumens of the seminiferous tubules, sperm move into the straight tubules (or tubuli recti), and from there into a fine meshwork of tubules called the rete testes. Sperm leave the rete testes, and the testis itself, through the 15 to 20 efferent ductules that cross the tunica albuginea.
Inside the seminiferous tubules are six different cell types. These include supporting cells called sustentacular cells, as well as five types of developing sperm cells called germ cells. Germ cell development progresses from the basement membrane—at the perimeter of the tubule—toward the lumen. Let’s look more closely at these cell types.
Surrounding all stages of the developing sperm cells are elongate, branching Sertoli cells. Sertoli cells are a type of supporting cell called a sustentacular cell, or sustentocyte, that are typically found in epithelial tissue. Sertoli cells secrete signaling molecules that promote sperm production and can control whether germ cells live or die. They extend physically around the germ cells from the peripheral basement membrane of the seminiferous tubules to the lumen. Tight junctions between these sustentacular cells create the blood–testis barrier, which keeps bloodborne substances from reaching the germ cells and, at the same time, keeps surface antigens on developing germ cells from escaping into the bloodstream and prompting an autoimmune response.
The least mature cells, the spermatogonia (singular = spermatogonium), line the basement membrane inside the tubule. Spermatogonia are the stem cells of the testis, which means that they are still able to differentiate into a variety of different cell types throughout adulthood. Spermatogonia divide to produce primary and secondary spermatocytes, then spermatids, which finally produce formed sperm. The process that begins with spermatogonia and concludes with the production of sperm is called spermatogenesis.
As just noted, spermatogenesis occurs in the seminiferous tubules that form the bulk of each testis (see Figure 27.4). The process begins at puberty, after which time sperm are produced constantly throughout a man’s life. One production cycle, from spermatogonia through formed sperm, takes approximately 64 days. A new cycle starts approximately every 16 days, although this timing is not synchronous across the seminiferous tubules. Sperm counts—the total number of sperm a man produces—slowly decline after age 35, and some studies suggest that smoking can lower sperm counts irrespective of age.
The process of spermatogenesis begins with mitosis of the diploid spermatogonia (Figure 27.5). Because these cells are diploid (2n), they each have a complete copy of the father’s genetic material, or 46 chromosomes. However, mature gametes are haploid (1n), containing 23 chromosomes—meaning that daughter cells of spermatogonia must undergo a second cellular division through the process of meiosis.
Figure 27.5 Spermatogenesis (a) Mitosis of a spermatogonial stem cell involves a single cell division that results in two identical, diploid daughter cells (spermatogonia to primary spermatocyte). Meiosis has two rounds of cell division: primary spermatocyte to secondary spermatocyte, and then secondary spermatocyte to spermatid. This produces four haploid daughter cells (spermatids). (b) In this electron micrograph of a cross-section of a seminiferous tubule from a rat, the lumen is the light-shaded area in the center of the image. The location of the primary spermatocytes is near the basement membrane, and the early spermatids are approaching the lumen (tissue source: rat).
Two identical diploid cells result from spermatogonia mitosis. One of these cells remains a spermatogonium, and the other becomes a primary spermatocyte, the next stage in the process of spermatogenesis. As in mitosis, DNA is replicated in a primary spermatocyte, before it undergoes a cell division called meiosis I. During meiosis I each of the 23 pairs of chromosomes separates. This results in two cells, called secondary spermatocytes, each with only half the number of chromosomes. Now a second round of cell division (meiosis II) occurs in both of the secondary spermatocytes. During meiosis II each of the 23 replicated chromosomes divides, similar to what happens during mitosis. Thus, meiosis results in separating the chromosome pairs. This second meiotic division results in a total of four cells with only half of the number of chromosomes. Each of these new cells is a spermatid. Although haploid, early spermatids look very similar to cells in the earlier stages of spermatogenesis, with a round shape, central nucleus, and large amount of cytoplasm. A process called spermiogenesis transforms these early spermatids, reducing the cytoplasm, and beginning the formation of the parts of a true sperm. The fifth stage of germ cell formation—spermatozoa, or formed sperm—is the end result of this process, which occurs in the portion of the tubule nearest the lumen. Eventually, the sperm are released into the lumen and are moved along a series of ducts in the testis toward a structure called the epididymis for the next step of sperm maturation.
Structure of Formed Sperm
Sperm are smaller than most cells in the body; in fact, the volume of a sperm cell is 85,000 times less than that of the female gamete. Approximately 100 to 300 million sperm are produced each day, whereas women typically ovulate only one oocyte per month. As is true for most cells in the body, the structure of sperm cells speaks to their function. Sperm have a distinctive head, mid-piece, and tail region (Figure 27.6). The head of the sperm contains the extremely compact haploid nucleus with very little cytoplasm. These qualities contribute to the overall small size of the sperm (the head is only 5 μm long). A structure called the acrosome covers most of the head of the sperm cell as a “cap” that is filled with lysosomal enzymes important for preparing sperm to participate in fertilization. Tightly packed mitochondria fill the mid-piece of the sperm. ATP produced by these mitochondria will power the flagellum, which extends from the neck and the mid-piece through the tail of the sperm, enabling it to move the entire sperm cell. The central strand of the flagellum, the axial filament, is formed from one centriole inside the maturing sperm cell during the final stages of spermatogenesis.
Figure 27.6 Structure of Sperm Sperm cells are divided into a head, containing DNA; a mid-piece, containing mitochondria; and a tail, providing motility. The acrosome is oval and somewhat flattened.
To fertilize an egg, sperm must be moved from the seminiferous tubules in the testes, through the epididymis, and—later during ejaculation—along the length of the penis and out into the female reproductive tract.
Role of the Epididymis
From the lumen of the seminiferous tubules, the immotile sperm are surrounded by testicular fluid and moved to the epididymis (plural = epididymides), a coiled tube attached to the testis where newly formed sperm continue to mature (see Figure 27.4). Though the epididymis does not take up much room in its tightly coiled state, it would be approximately 6 m (20 feet) long if straightened. It takes an average of 12 days for sperm to move through the coils of the epididymis, with the shortest recorded transit time in humans being one day. Sperm enter the head of the epididymis and are moved along predominantly by the contraction of smooth muscles lining the epididymal tubes. As they are moved along the length of the epididymis, the sperm further mature and acquire the ability to move under their own power. Once inside the female reproductive tract, they will use this ability to move independently toward the unfertilized egg. The more mature sperm are then stored in the tail of the epididymis (the final section) until ejaculation occurs.
During ejaculation, sperm exit the tail of the epididymis and are pushed by smooth muscle contraction to the ductus deferens (also called the vas deferens). The ductus deferens is a thick, muscular tube that is bundled together inside the scrotum with connective tissue, blood vessels, and nerves into a structure called the spermatic cord (see Figure 27.2 and Figure 27.3). Because the ductus deferens is physically accessible within the scrotum, surgical sterilization to interrupt sperm delivery can be performed by cutting and sealing a small section of the ductus (vas) deferens. This procedure is called a vasectomy, and it is an effective form of male birth control. Although it may be possible to reverse a vasectomy, clinicians consider the procedure permanent, and advise men to undergo it only if they are certain they no longer wish to father children.
From each epididymis, each ductus deferens extends superiorly into the abdominal cavity through the inguinal canal in the abdominal wall. From here, the ductus deferens continues posteriorly to the pelvic cavity, ending posterior to the bladder where it dilates in a region called the ampulla (meaning “flask”).
Sperm make up only 5 percent of the final volume of semen, the thick, milky fluid that the male ejaculates. The bulk of semen is produced by three critical accessory glands of the male reproductive system: the seminal vesicles, the prostate, and the bulbourethral glands.
As sperm pass through the ampulla of the ductus deferens at ejaculation, they mix with fluid from the associated seminal vesicle (see Figure 27.2). The paired seminal vesicles are glands that contribute approximately 60 percent of the semen volume. Seminal vesicle fluid contains large amounts of fructose, which is used by the sperm mitochondria to generate ATP to allow movement through the female reproductive tract.
The fluid, now containing both sperm and seminal vesicle secretions, next moves into the associated ejaculatory duct, a short structure formed from the ampulla of the ductus deferens and the duct of the seminal vesicle. The paired ejaculatory ducts transport the seminal fluid into the next structure, the prostate gland.
As shown in Figure 27.2, the centrally located prostate gland sits anterior to the rectum at the base of the bladder surrounding the prostatic urethra (the portion of the urethra that runs within the prostate). About the size of a walnut, the prostate is formed of both muscular and glandular tissues. It excretes an alkaline, milky fluid to the passing seminal fluid—now called semen—that is critical to first coagulate and then decoagulate the semen following ejaculation. The temporary thickening of semen helps retain it within the female reproductive tract, providing time for sperm to utilize the fructose provided by seminal vesicle secretions. When the semen regains its fluid state, sperm can then pass farther into the female reproductive tract.
The prostate normally doubles in size during puberty. At approximately age 25, it gradually begins to enlarge again. This enlargement does not usually cause problems; however, abnormal growth of the prostate, or benign prostatic hyperplasia (BPH), can cause constriction of the urethra as it passes through the middle of the prostate gland, leading to a number of lower urinary tract symptoms, such as a frequent and intense urge to urinate, a weak stream, and a sensation that the bladder has not emptied completely. By age 60, approximately 40 percent of men have some degree of BPH. By age 80, the number of affected individuals has jumped to as many as 80 percent. Treatments for BPH attempt to relieve the pressure on the urethra so that urine can flow more normally. Mild to moderate symptoms are treated with medication, whereas severe enlargement of the prostate is treated by surgery in which a portion of the prostate tissue is removed.
Another common disorder involving the prostate is prostate cancer. According to the Centers for Disease Control and Prevention (CDC), prostate cancer is the second most common cancer in men. However, some forms of prostate cancer grow very slowly and thus may not ever require treatment. Aggressive forms of prostate cancer, in contrast, involve metastasis to vulnerable organs like the lungs and brain. There is no link between BPH and prostate cancer, but the symptoms are similar. Prostate cancer is detected by a medical history, a blood test, and a rectal exam that allows physicians to palpate the prostate and check for unusual masses. If a mass is detected, the cancer diagnosis is confirmed by biopsy of the cells.
The final addition to semen is made by two bulbourethral glands (or Cowper’s glands) that release a thick, salty fluid that lubricates the end of the urethra and the vagina, and helps to clean urine residues from the penile urethra. The fluid from these accessory glands is released after the male becomes sexually aroused, and shortly before the release of the semen. It is therefore sometimes called pre-ejaculate. It is important to note that, in addition to the lubricating proteins, it is possible for bulbourethral fluid to pick up sperm already present in the urethra, and therefore it may be able to cause pregnancy.
The penis is the male organ of copulation (sexual intercourse). It is flaccid for non-sexual actions, such as urination, and turgid and rod-like with sexual arousal. When erect, the stiffness of the organ allows it to penetrate into the vagina and deposit semen into the female reproductive tract.
Figure 27.7Cross-Sectional Anatomy of the Penis Three columns of erectile tissue make up most of the volume of the penis.
The shaft of the penis surrounds the urethra (Figure 27.7). The shaft is composed of three column-like chambers of erectile tissue that span the length of the shaft. Each of the two larger lateral chambers is called a corpus cavernosum (plural = corpora cavernosa). Together, these make up the bulk of the penis. The corpus spongiosum, which can be felt as a raised ridge on the erect penis, is a smaller chamber that surrounds the spongy, or penile, urethra. The end of the penis, called the glans penis, has a high concentration of nerve endings, resulting in very sensitive skin that influences the likelihood of ejaculation (see Figure 27.2). The skin from the shaft extends down over the glans and forms a collar called the prepuce (or foreskin). The foreskin also contains a dense concentration of nerve endings, and both lubricate and protect the sensitive skin of the glans penis. A surgical procedure called circumcision, often performed for religious or social reasons, removes the prepuce, typically within days of birth.
Both sexual arousal and REM sleep (during which dreaming occurs) can induce an erection. Penile erections are the result of vasocongestion, or engorgement of the tissues because of more arterial blood flowing into the penis than is leaving in the veins. During sexual arousal, nitric oxide (NO) is released from nerve endings near blood vessels within the corpora cavernosa and spongiosum. Release of NO activates a signaling pathway that results in relaxation of the smooth muscles that surround the penile arteries, causing them to dilate. This dilation increases the amount of blood that can enter the penis and induces the endothelial cells in the penile arterial walls to also secrete NO and perpetuate the vasodilation. The rapid increase in blood volume fills the erectile chambers, and the increased pressure of the filled chambers compresses the thin-walled penile venules, preventing venous drainage of the penis. The result of this increased blood flow to the penis and reduced blood return from the penis is erection. Depending on the flaccid dimensions of a penis, it can increase in size slightly or greatly during erection, with the average length of an erect penis measuring approximately 15 cm.
Testosterone, an androgen, is a steroid hormone produced by Leydig cells. The alternate term for Leydig cells, interstitial cells, reflects their location between the seminiferous tubules in the testes. In male embryos, testosterone is secreted by Leydig cells by the seventh week of development, with peak concentrations reached in the second trimester. This early release of testosterone results in the anatomical differentiation of the male sexual organs. In childhood, testosterone concentrations are low. They increase during puberty, activating characteristic physical changes and initiating spermatogenesis.
Functions of Testosterone
The continued presence of testosterone is necessary to keep the male reproductive system working properly, and Leydig cells produce approximately 6 to 7 mg of testosterone per day. Testicular steroidogenesis (the manufacture of androgens, including testosterone) results in testosterone concentrations that are 100 times higher in the testes than in the circulation. Maintaining these normal concentrations of testosterone promotes spermatogenesis, whereas low levels of testosterone can lead to infertility. In addition to intratesticular secretion, testosterone is also released into the systemic circulation and plays an important role in muscle development, bone growth, the development of secondary sex characteristics, and maintaining libido (sex drive) in both males and females. In females, the ovaries secrete small amounts of testosterone, although most is converted to estradiol. A small amount of testosterone is also secreted by the adrenal glands in both sexes.
Control of Testosterone
The regulation of testosterone concentrations throughout the body is critical for male reproductive function. The intricate interplay between the endocrine system and the reproductive system is shown in Figure 27.8.
Figure 27.8 Regulation of Testosterone Production The hypothalamus and pituitary gland regulate the production of testosterone and the cells that assist in spermatogenesis. GnRH activates the anterior pituitary to produce LH and FSH, which in turn stimulate Leydig cells and Sertoli cells, respectively. The system is a negative feedback loop because the end products of the pathway, testosterone and inhibin, interact with the activity of GnRH to inhibit their own production.
The regulation of Leydig cell production of testosterone begins outside of the testes. The hypothalamus and the pituitary gland in the brain integrate external and internal signals to control testosterone synthesis and secretion. The regulation begins in the hypothalamus. Pulsatile release of a hormone called gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the endocrine release of hormones from the pituitary gland. Binding of GnRH to its receptors on the anterior pituitary gland stimulates release of the two gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These two hormones are critical for reproductive function in both men and women. In men, FSH binds predominantly to the Sertoli cells within the seminiferous tubules to promote spermatogenesis. FSH also stimulates the Sertoli cells to produce hormones called inhibins, which function to inhibit FSH release from the pituitary, thus reducing testosterone secretion. These polypeptide hormones correlate directly with Sertoli cell function and sperm number; inhibin B can be used as a marker of spermatogenic activity. In men, LH binds to receptors on Leydig cells in the testes and upregulates the production of testosterone.
A negative feedback loop predominantly controls the synthesis and secretion of both FSH and LH. Low blood concentrations of testosterone stimulate the hypothalamic release of GnRH. GnRH then stimulates the anterior pituitary to secrete LH into the bloodstream. In the testis, LH binds to LH receptors on Leydig cells and stimulates the release of testosterone. When concentrations of testosterone in the blood reach a critical threshold, testosterone itself will bind to androgen receptors on both the hypothalamus and the anterior pituitary, inhibiting the synthesis and secretion of GnRH and LH, respectively. When the blood concentrations of testosterone once again decline, testosterone no longer interacts with the receptors to the same degree and GnRH and LH are once again secreted, stimulating more testosterone production. This same process occurs with FSH and inhibin to control spermatogenesis.
Figure 27.1Ovulation Following a surge of luteinizing hormone (LH), an oocyte (immature egg cell) will be released into the uterine tube, where it will then be available to be fertilized by a male’s sperm. Ovulation marks the end of the follicular phase of the ovarian cycle and the start of the luteal phase.
Small, uncoordinated, and slick with amniotic fluid, a newborn encounters the world outside of her mother’s womb. We do not often consider that a child’s birth is proof of the healthy functioning of both her mother’s and father’s reproductive systems. Moreover, her parents’ endocrine systems had to secrete the appropriate regulating hormones to induce the production and release of unique male and female gametes, reproductive cells containing the parents’ genetic material (one set of 23 chromosomes). Her parent’s reproductive behavior had to facilitate the transfer of male gametes—the sperm—to the female reproductive tract at just the right time to encounter the female gamete, an oocyte (egg). Finally, combination of the gametes (fertilization) had to occur, followed by implantation and development. In this chapter, you will explore the male and female reproductive systems, whose healthy functioning can culminate in the powerful sound of a newborn’s first cry.