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SEXUAL DIFFERENTIATION

  1. Anatomic differentiation into male or female occurs in utero, but the final maturation of fully functional reproductive organs is not completed until puberty.

  2. The complement of sex chromosomes determines sexual differentiation.

    1. Female gametes (oocytes) all have a 22X chromosomal makeup, whereas male gametes (spermatozoa) are either 22X or 22Y.

    2. The chromosomal sex of the fetus is determined at fertilization when the male and female gametes combine; XX is female and XY is male.

  3. The default phenotypic sex of the fetus is female if it does not have a Y chromosome.

    1. The presence of a Y chromosome directs the undifferentiated gonad to become a testis rather than an ovary.

    2. A single gene (SRY), located in the sex-determining region of the Y chromosome, produces testis-determining factor that is required for male sexual differentiation.

  4. Before sexual differentiation, the fetus has two parallel duct systems located near the undifferentiated gonads: the mesonephric (Wolffian) duct and the paramesonephric (Müllerian) duct (Figure 9-1).

    1. By week 10 of gestation, the fetal gonads can be distinguished as either testes or ovaries.

    2. In males, the primordial germ cells give rise to precursors of male gametes called spermatogonia.

      1. The germinal epithelium that will later produce male gametes is formed by spermatogonia plus support cells called Sertoli cells.

      2. The surrounding mesenchyme becomes Leydig cells, which secrete testosterone.

    3. In females, the primordial germ cells give rise to precursors of female gametes called oogonia.

      1. The epithelium surrounding the oogonia differentiates into granulosa cells, and the surrounding ovarian mesenchyme becomes thecal cells.

      2. In the sexually mature female, estrogens and progestins are secreted by the granulosa and theca cells.

  5. Differentiation of the genitalia depends only on the presence or absence of hormones secreted by the testes.

    1. In the male fetus, the secretion of testosterone by Leydig cells directs each mesonephric duct to develop into an epididymis, a vas deferens, and a seminal vesicle.

    2. Leydig cells produce testosterone in response to the hormone human chorionic gonadotropin (hCG), which is secreted by the placenta.

    3. The developing Sertoli cells are directed by SRY to secrete Müllerian-inhibiting substance, causing regression of the Müllerian duct system.

    4. The absence of the Müllerian-inhibiting substance in the female fetus allows the Müllerian duct system (instead of the Wolffian duct) to develop, leading to formation of the fallopian tubes, the uterus, and the upper vagina.

    5. Fetal ovaries are not necessary for the development of the female genitalia due to the high concentration of maternal estrogens that are present during pregnancy.

  6. Undifferentiated external genitalia consist of a genital tubercle and a urogenital slit, bounded by two lateral genital folds and two labioscrotal swellings (Figure 9-2).

    1. In males, the conversion of testosterone to dihydrotestosterone, via the enzyme 5α-reductase within these target tissues, is necessary for formation of the prostate gland and the male external genitalia.

      1. The genital folds fuse to form the penis; the enlargement and fusion of the labioscrotal swellings form the scrotum.

      2. Descent of ...

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