Chapter 22 - Reproductive System

  Gametes and Chromosomes
     The sex cells  are called gametes and contain a single copy of each chromosome including one of the sex chromosomes. Male gametes are called spermatozoa (sing. spermatozoon), or simply sperm cells; female gametes are called ova (sing. ovum), or simply eggs.
     The gametes are haploid because they contain only a single copy of each chromosome, 22 autosomal chromosomes and one sex chromosome. During fertilization a male gamete fuses with a female gamete to form a new cell called a zygote. The zygote now has 22 pairs of autosomal chromosomes and two sex chromosomes and is diploid. Sex is determined by the presence of the Y sex chromosome with the male having an XY pair of sex chromosomes and the female, XX.
     The zygote undergoes mitotic division to form the new individual that has cells that are diploid. The new individual produces his/her own gametes by a process called gametogenesis.
   
  Meiosis
     Gametogenesis involves a process of cell division in which an individual's chromosomes are sorted and divided in a way that each daughter cell becomes haploid with each having a single copy of each autosomal chromosome and one sex chromosome.
     The process of meiosis can be broken down into the following steps: YouTube - Meiosis; Meiosis An Interactive Animation
  1. The process begins with a diploid (2n) germ cell containing 46 chromosomes.
  2. DNA replication occurs so that each chromosome has two identical copies of each chromosome called chromatids.
  3. Homologous chromosomes align so that paternal and maternal homologous chromosomes are next to one another.
  4. Crossing-over between homologous chromosomes occurs that causes homologous chromosomes to swap segments.
  5. Crossing-over creates new chromosomes with a mixture of paternal and maternal genes.
  6. Pairs of homologous chromosomes line up on either side of a plane bisecting the cell. Which member of each pair lines up on either side is independent of whether it is a maternal or a paternal chromosome. This is called independent assortment.
  7. The first meiotic division occurs which results in each daughter cell receiving one of each pair of homologous autosomal chromosomes and one sex chromosome. Each homologous chromosome contains two sister chromatids.
  8. The second meiotic division occurs which results in the sister chromatids separating so that each daughter cell contains one copy of each chromosome. Hence, the original germ cell, as a result of gametogenesis, yields four haploid gametes.
    
  Male Reproductive System
  Testes (Fig. 22.5)
     Each testis is divided into 250-300 compartments. Each compartment contains one to three highly coiled tubules called seminiferous tubules where gametogenesis occurs. The space between the tubules contains clusters of endocrine cells called Leydig or interstitial cells that produce androgens including testosterone.
     The wall of the seminiferous tubules consist of 3 to 5 layers of modified smooth muscle cells. These contractile cells exhibit contractions that help propel sperm and fluid through the tubule. The epithelium of the tubules consist of Sertoli cells that support the development of sperm cells and control their development. Germ cells undergoing meiosis to produce sperm cells are found in between the Sertoli cells. Mature sperm cells are found within the lumen of the tubules.
     The Sertoli cells are joined to one another by tight junctions that prevent cells of the blood's immune system from coming into contact with the sperm cells and the luminal fluid. This blood-testis barrier prevents an immune reaction to the newly formed antigens associated with the genetically distinct sperm cells.
     The Sertoli cells perform a number of other functions including:
  1. Secretion of the luminal fluid which nourishes and helps transport the sperm cells.
  2. Maintenance of a high concentration of androgen in the fluid of the luminal fluid by the production and secretion of androgen binding protein.
  3. Support the development of sperm cells by responding to testosterone and follicle stimulating hormone.
    Look at list in Table 22.1.
  Sperm Development (Fig. 22.8)
     Spermatogenesis begins with germ cells called spermatogonia (sing. spermatogonium). The spermatogonia, under the influence of rising levels of gonadotropins, continue to divide throughout the life of the male. The spermatogonia remain in the basal compartment of the seminiferous tubules where the cells divide by mitosis to replace themselves and to provide a population of cells that will eventually differentiate into primary spermatocytes.
     The primary spermatocyte undergoes the first division of meiosis. During this division crossing-over occurs which creates new genetic combinations. This results in the creation of molecules foreign to the body which if exposed to the blood would stimulate an immune reaction. However, the primary spermatocyte squeezes through the tight junctions between the Sertoli cells and enters the luminal compartment before this can happen. Upon completion of the first meiotic division, the primary spermatocyte has divided into two secondary spermatocytes that are haploid. Each secondary spermatocyte contains only one chromosome of each autosomal pair and one sex chromosome and each chromosome consists of two chromatids still attached by their respective centromeres. During the second division of meiosis, the chromatids of each chromosome separate as during mitosis and produce spermatids of which each contains only a single copy of each chromosome.
     The spermatids undergo differentiation to become spermatozoa, or sperm cells (Fig. 22.7). Sperm cells possess three distinct regions, a bulb-like head, a short cylindrical midpiece, and a long slender tail (flagellum). The head contains the nucleus and a large vesicle called an acrosome which contains enzymes and other proteins that enable a sperm cell to fuse with an egg during fertilization. The midpiece contains mitochondria which produce the ATP required for motility. The flagellum produces whip-like movements that give the sperm cells their motility.
     When sperm cells first form they are immotile and remain so for about 20 days. Motility is acquired as they are transported from the seminiferous tubules to the epididymis. Transport is due to peristaltic contractions of the seminiferous tubules and the flow of secretions produced by the seminiferous tubules.
  Hormonal Regulation of Reproductive Function (Fig. 22.6)

     The anterior pituitary releases two hormones that act upon the gonads of both males and females. These hormones are called gonadotropins and include follicle stimulating hormone (FSH) and luteinizing hormone (LH). The secretion of gonadotropins by the anterior pituitary is stimulated by gonadotropin releasing hormone (GNRH) produced by neurosecretory cells of the hypothalamus. Follicle stimulating hormone acts upon the Sertoli cells to stimulate spermatogenesis. LH stimulates secretion of androgens by Leydig cells.

     Androgens, such as testosterone, are steroids that diffuse locally to the seminiferous tubules to promote spermatogenesis. Androgens are also carried throughout the body as hormones in the blood stream. Testosterone limits its own production by negative feedback upon the cells of the hypothalamus that produce GNRH. The Sertoli cells also exert negative feedback upon the cells of the anterior pituitary that secrete FSH by way of a hormone called inhibin.
     The rates of sex hormone secretion in the male remain fairly constant throughout the reproductive life of the male. However, over the long term testosterone levels rise dramatically during puberty and reach a peak in the third decade of life and subsequently declines slowly.
   
  Female Reproductive System
     In contrast to the male reproductive system, the female system displays the following characteristics:
  1. The reproductive female undergoes monthly changes as part of a menstrual cycle. The cycle begins with menstruation which is marked by a shedding of blood and tissue from the uterine lining.
  2. A component of the menstrual cycle is the restricted period of time of only a few days during which an ovum is released and can be fertilized. This event occurs in the middle of the cycle and is called ovulation.
  3. Only about 400 ova are released during a woman's lifetime.
  Ovaries
     The ovaries are composed of connective tissue well supplied with blood vessels. The gametes are embedded within this connective tissue surrounded by supportive cells. The gametes with their supportive cells form structures called follicles. In the earliest stage of development of a follicle the follicle consists of a primary oocyte surrounded by single layer of flat cells called follicular cells. A follicle at this stage is called a primordial follicle.
     The gametes begin their development in the embryo as germ cells called oogonia (sing oogonium). The oogonia migrate into the ovaries during embryonic development from an extra-embryonic structure called the yolk sac. Even before birth, the number of oogonia is fixed in number and begin the process of differentiation called oogenesis (Fig. 22.12). Unlike spermatogonia, oogonia undergo mitosis only before birth to produce 2-4 million oogonia. These oogonia differentiate into primary oocytes that begin the first phase of meiosis. However, meiosis stops during prophase and does not restart until just before ovulation. This suspension of development is called meiotic arrest. At birth all gametes exist only as diploid primary oocytes in meiotic arrest within primordial follicles.
     At puberty, a monthly ovarian cycle begins in which a select number of primary oocytes begin to grow. The growth of these primary oocytes is supported by the surrounding follicular cells which begin to divide by mitosis and grow larger. When the follicular cells become cuboidal the enlarged follicle is called a primary follicle. As the follicle continues to enlarge, the supportive cells continue to divide until there is more than one layer of cells resting on the basement membrane that surrounds the follicle. When there is more than one layer of supportive cells these cells are no longer called follicular cells but are called instead granulosa cells. The cells which are immediately outside the basement membrane, and which surround the follicle, are called theca cells.
     The granulosa cells are similar to Sertoli cells in performing a number of supportive functions. Granulosa cells provide nutrients to the growing primary oocyte. Granulosa cells are stimulated by follicle stimulating hormone to divide and grow and secrete estrogen which promotes the growth of the oocyte. The granulosa cells in turn secrete inhibin which suppresses FSH secretion by the anterior pituitary. The estrogens secreted by the granulosa cells are actually synthesized from androgens that are supplied to the granulosa cells by the surrounding theca cells that secrete them.
     During the follicular phase of the ovarian cycle the primary oocyte and the follicle continue to grow. The granulosa cells secrete a fluid that separates them and coalesces to form a fluid-filled space called an antrum. This growth continues until just prior to ovulation when the follicle has grown quite large and the follicle is like a fluid-filled cyst with its enlarged antrum. Just prior to ovulation the primary oocyte restarts the first meiotic division to yield two haploid daughter cells. However, only one nucleus remains in the enlarged cell while the other nucleus is discarded as the first polar body. The cell that retain most of the cytoplasm is now called the secondary oocyte. The secondary oocyte enters the second division of meiosis but stops again during metaphase. The secondary oocyte, frozen in metaphase of meiosis II, is the cell that is extruded from the ovary during ovulation.
  Menstrual Cycle
     The menstrual cycle includes cyclic monthly changes in the ovaries and uterus that are controlled by hormones.
    Ovarian Cycle (Fig. 22.13)
     The ovarian cycle is divided into two phases:
  Follicular Phase
     The follicular phase begins at the start of menstruation and ends with ovulation and lasts for approximately 14 days. The ovary at this stage contains mostly primordial follicles but a small fraction of follicles have become primary follicles. A few follicles have grown further by enlarging and the granulosa cells have secreted a fluid that pushes the granulosa cells apart to form a fluid-filled space called the antrum. A follicle that has an antrum is called a secondary follicle.
     At the beginning of the follicular phase 10-25 secondary follicles in each ovary are recruited to develop further. After 7 days, one of these follicles, in one of the ovaries, becomes the dominant follicle. The follicle that becomes dominant is the follicle that can continue to produce adequate quantities of estrogen while plasma FSH is decreasing. The remaining follicles fail to produce enough estrogens and undergo degeneration in a process called atresia. The dominant follicle grows in size and becomes a mature or Graafian follicle. Just prior to ovulation the secondary oocyte, still surrounded by granulosa cells that form the corona radiata, is released into the antrum and is extruded when the follicle bursts open at the surface of the ovary. 
Luteal Phase
     The luteal phase begins with ovulation. The ruptured follicle is transformed into a corpus luteum. The development of the corpus luteum after ovulation is due to an abrupt rise in luteinizing hormone. The cells of the corpus luteum secrete estrogen and progesterone. If fertilization does not occur, the corpus luteum reaches maximum development at 10 days and then undergoes degeneration to become scar tissue called the corpus albicans. This degeneration causes a drop in estrogen and progesterone that causes menstruation. 
  Uterine Cycle
     The uterine cycle works in concert with the ovarian cycle and can be divided into three phases:
Menstrual Phase
     This phase begins on day 1 of the cycle and lasts for 3 to 5 days. This phase is defined by the shedding of the superficial lining of the endometrium of the uterus. A mixture of blood and sloughed tissue leaves the uterus, seeps into the vagina, and exits the body. 
Proliferative Phase
     During the proliferative phase the superficial endometrial lining is restored. The endometrial glands enlarge and blood vessels grow. This phase ends with ovulation. 
Secretory Phase
     During the secretory phase the endometrial glands enlarge further and secrete fluids rich in glycogen. The glandular secretion provides an environment favorable for the implantation and nourishment of the developing embryo. 
Hormonal Changes during the Menstrual Cycle (Fig. 22.15)
     The hormonal changes influence both the ovarian and uterine cycles simultaneously but the changes will be described with the ovarian cycle only. 
  Early to Mid-Follicular Phase
     At the beginning of the follicular phase, the plasma estrogen and progesterone levels have declined dramatically and are low. The decline in estrogen and progesterone decrease negative feedback (see Fig. 22.16) on the secretion of LH and FSH and as a consequence plasma levels of these hormones begin to rise
     FSH binds to receptors on granulosa cells and promotes their growth and proliferation. The theca cells also develop, become responsive to LH and release androgens. The androgens travel to the granulosa cells and are converted to estrogen. A dominant follicle emerges that secretes estrogen at a high rate so that estrogen plasma levels start to increase dramatically. Negative feedback causes plasma levels of LH and FSH to stop rising. However, increasing secretion of inhibin by granulosa cells cause a more dramatic drop in FSH. The drop in FSH causes atresia of non-dominant follicles. 
  Late Follicular Phase
     In the follicular phase, the rising levels of estrogen trigger a change in the way the hypothalamus and anterior pituitary respond to these hormones (Fig. 22.17). A positive feedback loop is created in which increasing levels of estrogen cause increasing levels of LH and FSH. As a result, there is a dramatic increase in plasma LH levels called the LH surge. The rising estrogen levels also cause the granulosa cells to become more responsive to LH by stimulating the expression of LH receptors. 
     The rising levels of LH cause the following changes in the dominant follicle:
1. The granulosa cells secrete paracrines that stimulate the primary oocyte to complete meiosis I
2. Estrogen levels decrease as estrogen secretion by the granulosa cells falls.
3. Granulosa cells begin to secrete progesterone.
4. Granulosa cells secrete enzymes and paracrines that cause the weakening of the follicular wall
5. Both granulosa and theca cells begin to differentiate into luteinized cells that form the corpus luteum.   
  Luteal Phase
     As the dominant follicle is transformed into a corpus luteum secretion of estrogen falls. Falling estrogen levels removes the stimulus for LH secretion and the LH surge ends. As the corpus luteum grows, it secretes more and more progesterone, and progesterone levels rise. Estrogen is also secreted by the corpus luteum and the levels of both hormones peak around the middle of the luteal phase. 
     Progesterone promotes the secretory phase of the uterus and other changes that prepare the body for a possible pregnancy (Table 22.4). 
     If a pregnancy does not occur by about the 10th day of the luteal phase, the corpus luteum begins to degenerate and its secretion of estrogen and progesterone decreases. The drop in estrogen and progesterone triggers menstruation. The rising levels of progesterone during the luteal phase suppresses secretion of FSH and LH and override any stimulatory effect estrogen might have during this phase (Fig. 22.18).