Sexual Reproduction

Early embryonic gonads can become either testes or ovaries. A particular gene on the Y chromosome induces the embryonic gonads to become testes. Females lack a Y chromosome, and the absence of this gene causes the development of ovaries.The embryonic testes secrete testosterone, which induces the development of male accessory sex organs and external genitalia.The absence of testes (rather than the presence of ovaries) in a female embryo causes the development of the female accessory sex organs.

"A chicken is an egg's way of making another egg." Phrased in more modern terms, genes are "selfish." Genes, according to this view, do not exist in order to make a well-functioning chicken (or other organism). The organism, rather, exists and functions so that the genes can survive beyond the mortal life of individual members of a species. Whether or not one accepts this rather cynical view, it is clear that reproduction is one of life's essential functions. The incredible complexity of structure and function in living organisms could not be produced in successive generations by chance; mechanisms must exist to transmit the blueprint (genetic code) from one generation to the next. Sexual reproduction, in which genes from two individuals are combined in random and novel ways with each new generation, offers the further advantage of introducing great variability into a population. This diversity of genetic constitution helps to ensure that some members of a population will survive changes in the environment over evolutionary time.

In sexual reproduction, germ cells, or gametes (sperm and ova), are formed within the gonads (testes and ovaries) by a process of reduction division, or meiosis (chapter 3). During this type of cell division, the normal number of chromosomes in human cells—forty-six—is halved, so that each gamete receives twenty-three chromosomes. Fusion of a sperm cell and ovum

Chapter Twenty

■ Figure 20.1 The human life cycle. Numbers in parentheses indicate the haploid state (twenty-three chromosomes) or diploid state (forty-six chromosomes).

(egg cell) in the act of fertilization results in restoration of the original chromosome number of forty-six in the zygote, or fertilized egg. Growth of the zygote into an adult member of the next generation occurs by means of mitotic cell divisions, as described in chapter 3. When this individual reaches puberty, mature sperm or ova will be formed by meiosis within the gonads so that the life cycle can be continued (fig. 20.1).

Sex Determination

Each zygote inherits twenty-three chromosomes from its mother and twenty-three chromosomes from its father. This does not produce forty-six different chromosomes, but rather twenty-three pairs of homologous chromosomes. The members of a homologous pair, with the important exception of the sex chromosomes, look like each other and contain similar genes (such as those coding for eye color, height, and so on). These homologous pairs of chromosomes can be photographed and numbered (as shown in fig. 20.2). Each cell that contains forty-six chromosomes (that is diploid) has two number 1 chromosomes, two number 2 chromosomes, and so on through pair number 22. The first twenty-two pairs of chromosomes are called autosomal chromosomes.

The twenty-third pair of chromosomes are the sex chromosomes. In a female, these consist of two X chromosomes, whereas in a male there is one X chromosome and one Y chromosome. The X and Y chromosomes look different and contain different genes. This is the exceptional pair of homologous chromosomes mentioned earlier.

When a diploid cell (with forty-six chromosomes) undergoes meiotic division, its daughter cells receive only one chromosome from each homologous pair of chromosomes. The

if IT

11

13

13

o.U ft ti

ra

is

tt

ta

1-3

M

A *#

70

■ Figure 20.2 Homologous pairs of chromosomes. These were obtained from diploid human cells. The first twenty-two pairs of chromosomes are called the autosomal chromosomes. The sex chromosomes are (a) XY for a male and (b) XX for a female.

gametes are therefore said to be haploid (they contain only half the number of chromosomes in the diploid parent cell). Each sperm cell, for example, will receive only one chromosome of homologous pair number 5—either the one originally contributed by the mother, or the one originally contributed by the father (modified by the effects of crossing-over; see chapter 3, fig. 3.34). Which of the two chromosomes—maternal or paternal—ends up in a given sperm cell is completely random. This is also true for the sex chromosomes, so that approximately half of the sperm produced will contain an X and approximately half will contain a Y chromosome.

The egg cells (ova) in a woman's ovary will receive a similar random assortment of maternal and paternal chromosomes. Since the body cells of females have two X chromosomes, however, all of the ova will normally contain one X chromosome. Because all ova contain one X chromosome, whereas some sperm are X-bearing and others are Y-bearing, the chromosomal sex of the zygote is determined by the fertilizing sperm cell. If a Y-bearing sperm cell fertilizes the ovum, the zygote will be XY and male; if an X-bearing sperm cell fertilizes the ovum, the zygote will be XX and female.

Although each diploid cell in a woman's body inherits two X chromosomes, it appears that only one of each pair of X chromosomes remains active. The other X chromosome forms a clump of inactive heterochromatin, which can often be seen as a dark spot, called a Barr body, in the nucleus of cheek cells (fig. 20.3). This provides a convenient test for chromosomal sex in cases where it is suspected that the chromosomal sex may differ from the apparent ("phenotypic") sex of the individual. Also, some of the nuclei in the neutrophils of females have a "drumstick" appendage not seen in neutrophils from males.

Formation of Testes and Ovaries

Following conception, the gonads of males and females are similar in appearance for the first forty or so days of development. During this time, cells that will give rise to sperm (called spermatogonia) and cells that will give rise to ova (called oogo-nia) migrate from the yolk sac to the developing embryonic go-nads. At this stage, the embryonic structures have the potential to become either testes or ovaries. The hypothetical substance that promotes their conversion to testes (fig. 20.4) has been called the testis-determining factor (TDF).

Although it has long been recognized that male sex is determined by the presence of a Y chromosome and female sex by the absence of the Y chromosome, the genes involved have only recently been localized. In rare male babies with XX genotypes, scientists have discovered that one of the X chromosomes contains a segment of the Y chromosome—the result of an error

■ Figure 20.3 Barr bodies. The nuclei of cheek cells from females (a) have Barr bodies (arrow). These are formed from one of the X chromosomes, which is inactive. No Barr body is present in the cell obtained from a male because males have only one X chromosome, which remains active. Some neutrophils obtained from females (b) have a "drumstick-like" appendage (arrow) that is not found in the neutrophils of males.

that occurred during the meiotic cell division that formed the sperm cell. Similarly, rare female babies with XY genotypes were found to be missing the same portion of the Y chromosome erroneously inserted into the X chromosome of XX males.

Through these and other observations, it has been shown that the gene for the testis-determining factor is located on the short arm of the Y chromosome. Evidence suggests that it may be a particular gene known as SRY (for sex-determining region of the Y). This gene is found in the Y chromosome of all mammals and is highly conserved, meaning that it shows little variation in structure over evolutionary time.

Notice that it is normally the presence or absence of the Y chromosome that determines whether the embryo will have testes or ovaries. This point is well illustrated by two genetic abnormalities. In Klinefelter's syndrome, the affected person has forty-seven instead of forty-six chromosomes because of the presence of an extra X chromosome. This person, with an XXY genotype, will develop testes and have a male phenotype despite the presence of two X chromosomes. Patients with Turner's syndrome, who have the genotype XO (and therefore have only forty-five chromosomes), have poorly developed ("streak") gonads and are phenotypically female.

The structures that will eventually produce sperm within the testes, the seminiferous tubules, appear very early in embryonic development—between 43 and 50 days following conception. The tubules contain two major cell types: germinal and nongerminal. The germinal cells are those that will eventually become sperm through meiosis and subsequent specialization. The nongerminal cells are called Sertoli (or sustentacular) cells. The Sertoli cells appear at about day 42. At about day 65, the Leydig (or interstitial) cells appear in the embryonic testes. The Leydig cells are clustered in the interstitial tissue that surrounds the seminiferous tubules. The interstitial Leydig cells constitute the endocrine tissue of the testes. In contrast to the rapid development of the testes, the functional units of the ovaries—called the ovarian follicles—do not appear until the second trimester of pregnancy (at about day 105).

Seminiferous tubules

Interstitial cells

Develop in early embryo

■ Figure 20.4 The chromosomal sex and the development of embryonic gonads. The very early embryo has "indifferent gonads" that can develop into either testes or ovaries. The testis-determining factor (TDF) is a gene located on the Y chromosome. In the absence of TDF, ovaries will develop.

The early-appearing Leydig cells in the embryonic testes secrete large amounts of male sex hormones, or androgens (andro = man; gen = forming). The major androgen secreted by these cells is testosterone. Testosterone secretion begins as early as 8 weeks after conception, reaches a peak at 12 to 14 weeks, and then declines to very low levels by the end of the second trimester (at about 21 weeks). Testosterone secretion during embryonic development in the male serves the very important function of masculinizing the embryonic structures; similarly high levels of testosterone will not appear again in the life of the individual until the time of puberty.

Testosterone

No testosterone No MIF

Degenerates -

Penis, scrotum'

Müllerian inhibition factor (MIF)

Epididymides, Testosterone ductus deferentia, -

ejaculatory ducts

Testosterone

Paramesonephric duct

Mesonephric duct structures

(No testosterone)

Uterus, uterine tubes

Degenerates

Other embryonic (No testosterone) Vagina, labia, clitoris

■ Figure 20.5 The regulation of embryonic sexual development. In the presence of testosterone and mullerian inhibition factor (MIF) secreted by the testes, male external genitalia and accessory sex organs develop. In the absence of these secretions, female structures develop.

As the testes develop, they move within the abdominal cavity and gradually descend into the scrotum. Descent of the testes is sometimes not complete until shortly after birth. The temperature of the scrotum is maintained at about 35° C—about 3° C below normal body temperature. This cooler temperature is needed for spermatogenesis. The fact that spermatogenesis does not occur in males with undescended testes—a condition called cryptorchidism (crypt = hidden; orchid = testes)—demonstrates this requirement.

Associated with each spermatic cord is a strand of skeletal muscle called the cremaster muscle. In cold weather, the cremaster muscles contract and elevate the testes, bringing them closer to the warmth of the trunk. The cremasteric reflex produces the same effect when the inside of a man's thigh is stroked. In a baby, however, this stimulation can cause the testes to be drawn up through the inguinal canal into the body cavity. The testes can also be drawn up into the body cavity voluntarily by trained Sumo wrestlers.

Development of Accessory Sex Organs and External Genitalia

In addition to testes and ovaries, various internal accessory sex organs are needed for reproductive function. Most of these are derived from two systems of embryonic ducts. Male accessory organs are derived from the wolffian (mesonephric) ducts, and female accessory organs are derived from the mullerian (paramesonephric) ducts (fig. 20.5). Interestingly, the two duct systems are present in both male and female embryos between day 25 and day 50, and so embryos of both sexes have the potential to form the accessory organs characteristic of either sex.

Experimental removal of the testes (castration) from male embryonic animals results in regression of the wolffian ducts and development of the mullerian ducts into female accessory organs: the uterus and uterine (fallopian) tubes. Female accessory sex organs, therefore, develop as a result of the absence of testes rather than as a result of the presence of ovaries.

In a male, the Sertoli cells of the seminiferous tubules secrete mullerian inhibition factor (MIF), a polypeptide that causes regression of the mullerian ducts beginning at about day 60. The secretion of testosterone by the Leydig cells of the testes subsequently causes growth and development of the wolf-fian ducts into male accessory sex organs: the epididymis, ductus (vas) deferens, seminal vesicles, and ejaculatory duct.

The external genitalia of males and females are essentially identical during the first 6 weeks of development, sharing in common a urogenital sinus, genital tubercle, urethral folds, and a pair of labioscrotal swellings. The secretions of the testes masculinize these structures to form the penis and spongy (penile) urethra, prostate, and scrotum. In the absence of secreted testosterone, the genital tubercle that forms the penis in a male will become the clitoris in a female. The penis and clitoris are thus said to be homologous structures. Similarly, the labioscrotal swellings form the scrotum in a male or the labia majora in a female; these structures are therefore homologous also (fig. 20.6).

Labioscrotal swelling

Genital tubercle

Urethral folds

Labioscrotal swellings

Male

Developing ! penis

Glans penis

Scrotum

Scrotal raphe

Glans

Phallus

Glans

Phallus

Male

Developing ! penis

Glans penis

Scrotum

Scrotal raphe

Developing glans clitoris

Labia minora Labia majora

Glans clitoris Hymen

Vaginal orifice

Female

Developing glans clitoris

Labia minora Labia majora

Glans clitoris Hymen

Vaginal orifice

■ Figure 20.6 The development of the external genitalia in the male and female. (a [ai, sagittal view]) At 6 weeks, the urethral fold and labioscrotal swelling have differentiated from the genital tubercle. (b) At 8 weeks, a distinct phallus is present during the indifferent stage. By week 12, the genitalia have become distinctly male (c) or female (d), being derived from homologous structures. (e, f) At 16 weeks, the genitalia are formed.

Masculinization of the embryonic structures described occurs as a result of testosterone secreted by the embryonic testes. Testosterone itself, however, is not the active agent within all of the target organs. Once inside particular target cells, testosterone is converted by the enzyme 5a-reductase into the active hormone known as dihydrotestosterone (DHT) (fig. 20.7). DHT is needed for the development and maintenance of the penis, spongy urethra, scrotum, and prostate. Evidence suggests that testosterone itself directly stimulates the wolffian duct derivatives—epididymis, ductus deferens, ejaculatory duct, and seminal vesicles.

In summary, the genetic sex is determined by whether a Y-bearing or an X-bearing sperm cell fertilizes the ovum; the

Reproduction presence or absence of a Y chromosome in turn determines whether the gonads of the embryo will be testes or ovaries; the presence or absence of testes, finally, determines whether the accessory sex organs and external genitalia will be male or female (table 20.1). This regulatory pattern of sex determina-

tion makes sense in light of the fact that both male and female embryos develop within an environment high in estrogen, which is secreted by the mother's ovaries and the placenta. If the secretions of the ovaries determined the sex, all embryos would be female.

■ Figure 20.7 The formation of DHT. Testosterone, secreted by the interstitial (Leydig) cells of the testes, is converted into dihydrotestosterone (DHT) within the target cells. This reaction involves the addition of a hydrogen (and the removal of the double carbon bond) in the first (A) ring of the steroid.

Disorders of Embryonic Sexual Development

Hermaphroditism is a condition in which both ovarian and testicular tissue is present in the body. About 34% of hermaphrodites have an ovary on one side and a testis on the other. About 20% have ovotestes—part testis and part ovary— on both sides. The remaining 46% have an ovotestis on one side and an ovary or testis on the other. This condition is extremely rare and appears to be caused by the fact that some embryonic cells receive the short arm of the Y chromosome, with its SRY gene, whereas others do not. More common (though still rare) disorders of sex determination involve individuals with either testes or ovaries, but not both, who have accessory sex organs and external genitalia that are incompletely developed or that are inappropriate for their chromosomal sex. These individuals are called pseudohermaphrodites (pseudo = false).

The most common cause of female pseudohermaphroditism is congenital adrenal hyperplasia. This condition, which is inherited as a recessive trait, is caused by the excessive secretion of androgens from the adrenal cortex. Because the cortex does not secrete mullerian inhibition factor, a female with this condition would have mullerian duct derivatives (uterus and fallopian tubes), but she would also have wolffian duct derivatives and partially masculinized external genitalia.

Table 20.1 A Developmental Timetable for the Reproductive System

Approximate Time After Fertilization Developmental Changes

Days

Trimester

Indifferent

Male

Female

19

First

Germ cells migrate from yolk sac.

25-30

Wolffian ducts begin development.

44-48

Mullerian ducts begin development.

50-52

Urogenital sinus and tubercle develop.

53-60

Tubules and Sertoli cells appear.

Mullerian ducts begin to regress.

60-75

Leydig cells appear and begin

Formation of vagina begins.

testosterone production.

Wolffian ducts grow.

Regression of wolffian ducts begins.

105 120 160-260

Second Third

Testes descend into scrotum. Growth of external genitalia occurs.

Development of ovarian follicles begins.

Uterus is formed.

Formation of vagina is complete.

Source: Reproduced, with permission, from the Annual Review of Physiology, Volume 40, p. 279. Copyright © 1978 by Annual Reviews, Inc.

Source: Reproduced, with permission, from the Annual Review of Physiology, Volume 40, p. 279. Copyright © 1978 by Annual Reviews, Inc.

An interesting cause of male pseudohermaphroditism is testicular feminization syndrome. Individuals with this condition have normally functioning testes but lack receptors for testosterone. Thus, although large amounts of testosterone are secreted, the embryonic tissues cannot respond to this hormone. Female genitalia therefore develop, but the vagina ends blindly (a uterus and fallopian tubes do not develop because of the secretion of mullerian inhibition factor). Male accessory sex organs likewise cannot develop because the wolffian ducts lack testosterone receptors. A child with this condition appears externally to be a normal prepubertal girl, but she has testes in her body cavity and no accessory sex organs. These testes secrete an exceedingly large amount of testosterone at puberty because of the absence of negative feedback inhibition. This abnormally large amount of testosterone is converted by the liver and adipose tissue into estrogens. As a result, the person with testicular feminization syndrome develops into a female with well-developed breasts who never menstruates (and who, of course, can never become pregnant).

Some male pseudohermaphrodites have normally functioning testes and normal testosterone receptors, but they genetically lack the ability to produce the enzyme 5a-reductase. Individuals with 5a-reductase deficiency have normal epididymides, ductus (vasa) deferentia, seminal vesicles, and ejacu-latory ducts because the development of these structures is stimulated directly by testosterone. The external genitalia are poorly developed and more female in appearance, however, because DHT, which cannot be produced from testosterone in the absence of 5a-reductase, is required for the development of male external genitalia.

Chapter Twenty

Hearing Aids Inside Out

Hearing Aids Inside Out

Have you recently experienced hearing loss? Most probably you need hearing aids, but don't know much about them. To learn everything you need to know about hearing aids, read the eBook, Hearing Aids Inside Out. The book comprises 113 pages of excellent content utterly free of technical jargon, written in simple language, and in a flowing style that can easily be read and understood by all.

Get My Free Ebook


Post a comment