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2. Conception

Of the 200 X 106 sperm that are deposited in the vagina during coitus, only approximately 100-200 sperm reach the distal one-third of the fallopian tubes (see Figure 13-1) where fertilization normally occurs. The species specificity of the fertilization process is determined by a receptor-like mechanism present in the vitelline membrane of the ovum. W. Lennarz and associates have isolated a glycoprotein from sea urchin egg membranes that will only cross-react with a species-specific protein, termed bindin, present on the surface of a homologous sea urchin spermatozoon.

The attachment of a single spermatozoon to any region of the zona pellucida on a single ovum is the formal process of fertilization; the entire spermatozoon then enters the ovum, so that there is both a nuclear and a cytoplasmic contribution to the zygote. After sperm penetration, the fertilized ovum forms the second polar body (see also Figure 13-3). This is followed by the formation of female and male pronuclei; fusion of these haploid nuclei then creates, for the first time, the diploid nuclei of a totally new and unique individual. Some 30 hr later the first mitotic cleavage occurs, yielding a zygote with two cells; then within another 10 hr mitotic cleavage occurs again, producing a 4-cell state. Within 50-60 hr after fertilization the morula arises, followed by the blastocyst at 3-4 days (see Figures 14-1 and 14-2).

B. Sex Determination

1. Definition of Sex

Union of the spermatozoon with the ovum not only restores the diploid number of chromosomes (46 in humans) but also determines the genetic sex of the new individual. Since the oocyte always has an X chromosome, the sex of the offspring is determined by the fertilizing spermatozoon; if it is an X-bearing spermatozoon, the sex will be female (XX), while if it is a Y-bearing spermatozoon, the sex will be male (XY).

Under normal circumstances of the union of the human spermatozoon with the secondary oocyte, there is the creation of a zygote with 46 chromosomes. However, in some instances there are chromosomal abnormalities that may result in the offspring having an incorrect number of either autosomal chromosomes or sex chromosomes. Some of these abnormalities are summarized in Table 14-4. It is beyond the scope of this chapter to consider in detail the wide array of endocrine and nonendocrine disorders resulting from perturbations of genetic mechanisms of sexual development. The interested reader is referred to the review by Grumbach et al. (1992).

There are several other parameters besides the genetic sex that are utilized in describing the total definition of the sex of an individual. These are summarized in Table 14-5. Gonadal sex is a reflection of the morphology of the gonads and the hormones that they elaborate and is of dominant practical importance in defining the sex of an individual. Phenotypic sex is a reflection of the appearance of the external genitalia (i.e., the penis and vulva) as well as the secondary sex characteristics, including the beard and breasts, while somatic sex reflects the difference in the structures of the internal sex organs. Finally, psychological sex is a reflection of the social environment and behavioral aspects in which an individual may be raised.

TABLE 14-5 Parameters Involved with the Definition of Sex

Parameter

Description

Physiological sex Genetic or gender

Gonadal Somatic

Phenotypic

Birth certificate

Nonphysiological sex Psychological

Interaction of sex chromosomes XY = 6, XX = 5

Comparison of ovaries with testes Comparison of the internal sex organs in the male and female Comparison of the external genitalia and secondary sex characteristics: male, penis, beard; female, vulva, breasts Legal document usually certified by the physician present at birth, but may not correctly state the gonadal or genetic sex of the individual

Reflection of the social dimensions around the individual as she/he is reared, which may also reflect behavioral attitudes of key individuals in the environment

Hormones, Second Edition

In the instance of individuals who are transsexuals, transvestites, and homosexuals, their physiological sex may not agree with their psychological sex. Thus, when an individual experiences normal development and sexual differentiation and is exposed to a normal psychosocial environment, then her/his genetic, gonadal, somatic, phenotypic, and psychological sexes will match. However, disturbances in any one of these parameters can result in aberrant gender identification and pose serious clinical, endocrinological, and psychological problems.

2. Sex Differentiation

The ultimate purpose of sex differentiation is to produce a female or male of the species. While the genetic sex of the new offspring is determined at fertilization, no morphological differences in the reproductive system of the embryo can be detected until the initiation of sexual differentiation and appearance of characteristic gonadal sex attributes at approximately the fourth week of development.

The gonadal anlage or gonadal precursor cells can be identified in the 4-week-old embryo and are preformed from the coelomic epithelium and from condensation with its underlying mesenchyme. At this stage, since it is impossible to distinguish whether the gonadal anlage will differentiate into ovaries or testes, it is designated as an "indifferent gonadal anlage."

The indifferent anlage has two putative genital ducts: the Miillerian ducts, which can ultimately become the internal reproductive tract of the adult female, and the Wolffian ducts and mesonephros, which can become the adult male internal reproductive system. If the embryo is destined to become a male, the Miillerian ducts degenerate, while if the embryo is destined to become a female, the Wolffian ducts degenerate.

There is an inherent tendency for the indifferent gonadal anlage to undergo differentiation to yield ovaries provided that the correct X chromosome is present. The production of the male gonads, the testes, is believed to be related to the SKY gene (for sex-determining region Y), which is located on the Y chromosome (see the following). The chronology of these relationships is diagrammed schematically in Figure 14-14. The indifferent gonads begin to develop in the male at 43-50 days and in the female slightly later at 50-60 days.

Figure 14-15 diagrams the steps of human sex determination that lead to the conversion of the indifferent gonad anlage into either a testis or an ovary. This process of gonad differentiation is determined by the individual's genetic sex, and it is the subsequent male or female gonadal secretions that determine the somatic and phenotypic sexes. Figure 14-16 diagrams the reciprocal changes occurring in the male and female with respect to either Wolffian or Miillerian duct development.

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