- Reproduction is the process by which a species is perpetuated.
- Reproduction is one of the few physiological processes that is not necessary for the survival of an individual.
- However, normal reproductive function is essential for the production of healthy offspring and, therefore, for survival of the species.
- Sexual reproduction and the merging of parental chromosomes provide the biological variation of individuals that is necessary for adaptation of the species to our changing environment.
- Reproduction also includes the process by which a fetus is born.
- Over the course of a lifetime, reproductive functions also include sexual maturation (puberty), as well as pregnancy and lactation in women.
The primary reproductive organs
- The primary reproductive organs are known as the gonads: the testes (singular, testis) in the male and the ovaries (singular, ovary) in the female.
- In both sexes, the gonads serve dual functions.
- 1. The first of these is gametogenesis, which is the production of the reproductive cells, or gametes.
- These are spermatozoa (singular, spermatozoan, usually shortened to sperm) in males and ova (singular, ovum) in females.
- 2. Secondly, the gonads secrete steroid hormones, often termed sex hormones or gonadal steroids.
- The major sex hormones are androgens (including testosterone and dihydrotestosterone [DHT]), estrogens (primarily estradiol), and progesterone.
- Both sexes have each of these hormones, but androgens predominate in males and estrogens and progesterone predominate in females.
- Gametogenesis: the production of the reproductive cells, or gametes (sperm/ovum)
- At any point in gametogenesis, the developing gametes are called germ cells.
- 1. The first stage in gametogenesis is proliferation of the primordial (undifferentiated) germ cells by mitosis.
- With the exception of the gametes, the DNA of each nucleated human cell is contained in 23 pairs of chromosomes, giving a total of 46.
- The two corresponding chromosomes in each pair are said to be homologous to each other, with one coming from each parent.
- 2. The second stage of gametogenesis is meiosis, in which each resulting gamete receives only 23 chromosomes from a 46-chromosome germ cell, one chromosome from each homologous pair.
- Mitosis: The first stage in gametogenesis is proliferation of the primordial (undifferentiated) germ cells by mitosis.
- In mitosis, the 46 chromosomes of the dividing cell are replicated.
- The cell then divides into two new cells called daughter cells.
- Each of the two daughter cells resulting from the division receives a full set of 46 chromosomes identical to those of the original cell.
- In this manner, mitosis of primordial germ cells, each containing 46 chromosomes, provides a supply of identical germ cells for the next stages.
- The timing of mitosis in germ cells differs greatly in females and males.
- In the male, some mitosis occurs in the embryonic testes to generate the population of primary spermatocytes present at birth, but mitosis really begins in earnest in the male at puberty and usually continues throughout life.
- In the female, mitosis of germ cells in the ovary occurs primarily during fetal development, generating primary oocytes.
- The second stage of gametogenesis is meiosis, in which each resulting gamete receives only 23 chromosomes from a 46-chromosome germ cell, one chromosome from each homologous pair.
- Meiosis consists of two cell divisions in succession.
- The events preceding the first meiotic division are identical to those preceding a mitotic division.
- During the interphase period, which precedes a mitotic division, chromosomal DNA is replicated.
- Therefore, after DNA replication, an interphase cell has 46 chromosomes, but each chromosome consists of two identical strands of DNA, called sister chromatids, which are joined together by a centromere.
- Prophase I: As the first meiotic division begins, homologous chromosomes, each consisting of two identical sister chromatids, come together and line up adjacent to each other.
- This results in the formation of 23 pairs of homologous chromosomes called bivalents.
- The sister chromatids of each chromosome condense into thick, rodlike structures.
- Then, within each homologous pair, corresponding segments of homologous chromosomes align closely.
- This allows two non-sister chromatids to undergo an exchange of sites of breakage in a process called crossing-over.
- Following crossing-over, the homologous chromosomes line up in the center of the cell. The orientation of each pair on the equator is random, meaning that sometimes the maternal portion points to a particular pole of the cell and sometimes the paternal portion does so.
- The cell then divides (the first meiotic division), with the maternal chromatids of any particular pair going to one of the two cells resulting from the division and the paternal chromatids going to the other.
- The results of the first meiotic division are the secondary spermatocytes in males and the secondary oocyte in females.
- Note in Figure 17.1 that, in females, one of the two cells arising from the first meiotic division is the first polar body that has no function and eventually degrades.
- Because of the random orientation of the homologous pairs at the equator, it is extremely unlikely that all 23 maternal chromatids will end up in one cell and all 23 paternal chromatids in the other.
- Over 8 million different combinations of maternal and paternal chromosomes can result during this first meiotic division.
- The second meiotic division occurs without any further replication of DNA.
- The sister chromatids—both of which were originally either maternal or paternal—of each chromosome separate and move apart into the new daughter cells.
- The daughter cells resulting from the second meiotic division, therefore, contain 23 one-chromatid chromosomes.
- Although the concept is the same, the timing of the second meiotic division is different in males and females.
- In males, this occurs continuously after puberty with the production of spermatids and ultimately mature sperm cells described in detail in the next section.
- In females, the second meiotic division does not occur until after fertilization of a secondary oocyte by a sperm.
- This results in production of the zygote, which contains 46 chromosomes—23 from the oocyte (maternal) and 23 from the sperm (paternal)—and the second polar body, which, like the first polar body, has no function and will degrade.
Causes of genetic variability
- To summarize, gametogenesis produces daughter cells having only 23 chromosomes, and two events during the first meiotic division contribute to the enormous genetic variability of the daughter cells
- (1) crossing-over and
- (2) the random distribution of maternal and paternal chromatid pairs between the two daughter cells.
17.2 Sex Determination
- The complete genetic composition of an individual is known as the genotype.
- Genetic inheritance sets the sex of the individual, or sex determination, which is established at the moment of fertilization.
- Sex is determined by genetic inheritance of two chromosomes called the sex chromosomes. The larger of the sex chromosomes is called the X chromosome and the smaller, the Y chromosome.
- Males possess one X and one Y, whereas females have two X chromosomes. Therefore, the key difference in genotype between males and females arises from this difference in one chromosome.
- As you will learn in the next section, the presence of the Y chromosome leads to the development of the male gonads— the testes; the absence of the Y chromosome leads to the development the female gonads—the ovaries.
- The ovum can contribute only an X chromosome, whereas half of the sperm produced during meiosis are X and half are Y.
- When the sperm and the egg join, 50% should have XX and 50% XY. Interestingly, however, sex ratios at birth are not exactly 1:1; rather, there tends to be a slight preponderance of male births, possibly due to functional differences in sperm carrying the X versus Y chromosome.
- When two X chromosomes are present, only one is functional; the nonfunctional X chromosome condenses to form a nuclear mass called the sex chromatin, or Barr body, which can be observed with a light microscope.
- Scrapings from the cheek mucosa or white blood cells are convenient sources of cells to be examined. The single X chromosome in male cells rarely condenses to form sex chromatin.
- A more exacting technique for determining sex chromosome composition called a karyotype employs tissue culture visualization of all the chromosomes.
- This technique can be used to identify a group of genetic sex abnormalities characterized by such unusual chromosomal combinations such as XXX, XXY, and XO (the O denotes the absence of a second sex chromosome).
- The end result of such combinations is usually the failure of normal anatomical
- and functional sexual development.
- The karyotype is also used to evaluate many other chromosomal abnormalities such as the characteristic trisomy 21 of Down syndrome described later in this chapter.
- The typical male is 46,XY male where 46 is the total number of chromosomes in each nucleated cell, the letters indicate the sex chromosomes, and male indicates the phenotype. The typical female, therefore, is 46,XX female.
17.3 Sex Differentiation
- The multiple processes involved in the development of the reproductive system in the fetus are collectively called sex differentiation.
- It is not surprising that people with atypical chromosomal combinations can manifest atypical sex differentiation.
- However, there are individuals with chromosomal combinations that do not match their sexual appearance and function (phenotype).
- In these people, sex differentiation has been atypical, and their sexual phenotype may not correspond with the presence of XX or XY chromosomes.
- The genes directly determine only whether the individual will have testes or ovaries.
- The rest of sex differentiation depends upon the presence or absence of substances produced by the genetically determined gonads, in particular, the testes.
Differentiation of the Gonads
- The male and female gonads derive embryologically from the same site—an area called the urogenital (or gonadal) ridge.
- Until the sixth week of uterine life, primordial gonads are undifferentiated (see Figure 17.2).
- In the genetic male, the testes begin to develop during the seventh week.
- A gene on the Y chromosome (the SRY gene, for sex-determining region of the Y chromosome) is expressed at this time in the urogenital ridge cells and triggers this development.
- In the absence of a Y chromosome and, consequently, the SRY gene, testes do not develop. Instead, ovaries begin to develop in the same area.
- The SRY gene codes for the SRY protein, a DNA-binding transcription factor that sets into motion a sequence of gene activations ultimately leading to the formation of testes from the various embryonic cells in the urogenital ridge.
Differentiation of Internal and External Genitalia
- The internal duct system and external genitalia of the fetus are capable of developing into either sexual phenotype.
- Before the fetal gonads are functional, the undifferentiated reproductive tract includes a double genital duct system, comprised of the Wolffian ducts and Müllerian ducts, and a common opening to the outside for the genital ducts and urinary system.
- Usually, most of the reproductive tract develops from only one of these duct systems. In the male, the Wolffian ducts persist and the Müllerian ducts regress, whereas in the female, the opposite happens.
- The external genitalia in the two sexes and the outer part of the vagina do not develop from these duct systems, however, but from other structures at the body surface.
- Which of the two duct systems and types of external genitalia develops depends on the presence or absence of fetal testes.
Disorders of Sexual Differentiation: androgen insensitivity syndrome
- There are various conditions in which normal sex differentiation does not occur.
- For example, in androgen insensitivity syndrome (formerly called testicular feminization), the genotype is XY and testes are present but the phenotype (external genitalia and vagina) is female (46, XY female).
- It is caused by a mutation in the androgen-receptor gene that renders the receptor incapable of normal binding to testosterone.
- Under the influence of SRY protein, the fetal testes differentiate as usual and they secrete both AMH and testosterone.
- AMH causes the Müllerian ducts to regress, but the inability of the Wolffian ducts to respond to testosterone also causes them to regress, and so no duct system develops.
- The tissues that develop into external genitalia are also unresponsive to androgen, so female external genitalia and a vagina develop.
- The testes do not descend, and they are usually removed when the diagnosis is made.
- The syndrome is typically not detected until menstrual cycles fail to begin at puberty.
Disorders of Sexual Differentiation: congenital adrenal hyperplasia
- Congenital adrenal hyperplasia is caused by the production of too much androgen in the fetus.
- Rather than the androgen coming from the fetal testes, it is caused by adrenal androgen overproduction due to a partial defect in the ability of the fetal adrenal gland to synthesize cortisol.
- This is almost always due to a mutation in the gene for an enzyme in the cortisol synthetic pathway leading to a partial decrease in the activity of the
- The resultant decrease in cortisol in the fetal blood leads to an increase in the secretion of ACTH from the fetal anterior pituitary gland due to a loss of glucocorticoid negative feedback.
- The increase in fetal plasma ACTH stimulates the fetal adrenal cortex to make more cortisol to overcome the partial enzyme dysfunction.
- Remember, however, that the adrenal cortex can synthesize androgens from the same precursor as cortisol.
- ACTH stimulation results in an increase in androgen production because the precursors cannot be efficiently converted to cortisol.
- This increase in fetal androgen production results in virilization of an XX fetus (masculinized external genitalia).
- If untreated in the fetus, the XX newborn can have ambiguous genitalia— it is not obvious whether the baby is a phenotypic boy or girl. These babies require treatment with cortisol replacement.
Disorders of Sexual Differentiation: unequal crossing over
- Rarely, unequal crossing over can result in the insertion of the SRY gene from the Y chromosome into the X chromosome.
- Although there are variations in the phenotype, an XX fetus who inherits an X-chromosome containing the SRY gene has an XX karyotype with a male phenotype (46,XX male).
- An individual who inherits the Y-chromosome missing the SRY gene will have an XY karyotype but a female phenotype (46,XY female).
Fetal and Neonatal Programming
- Classic Mendelian inheritance teaches us that one’s genetic attributes are established at conception when the maternal and paternal gametes join together.
- It is now known that early life experiences can alter the expression of many genes in later life. This is called epigenetics or epigenetic programming.
- Among the causes of these changes in gene expression are changes in intrauterine environment caused by, for example, maternal malnutrition.
- Neonatal stressors such as a premature birth are also known to affect
- the adult phenotype through epigenetic mechanisms.
- The mechanisms of this effect include changes in methylation of specific genes, histone modifications, and the presence of alternate forms of RNA that affect the translation of messenger RNA into protein.
- Among the adult phenotypes that have been shown to be influenced by early life stressors include the incidence of high blood pressure and type 2 diabetes mellitus.
- Another fascinating aspect of this is that these epigenetic changes can be transmitted to the next generation; that is, they can be inherited by the offspring of the affected adult.
- Although the field of epigenetics is relatively new, there is intensive research that will hopefully lead to new therapies to help prevent the inheritance of adult diseases that are not due to specific gene mutations but, rather, to changes in gene expression that were due to epigenetic modifications.
Sexual Differentiation of the Brain
- With regard to sexual behavior, differences in the brain may form during fetal and neonatal development.
- For example, genetic female monkeys treated with testosterone during their late fetal life manifest evidence of masculine sex behavior as adults, such as mounting.
- In this regard, a potentially important difference in human brain anatomy has been reported; the size of a particular nucleus (neuronal cluster) in the hypothalamus is significantly larger in men.
- There is also an increase in gonadal steroid secretion in the first year of postnatal life in the male that contributes to the sexual differentiation of the brain.
- Sex-linked differences in appearance or form within a species are called sexual dimorphisms.