USMLE Step 1 Lecture Notes 2018: 7-Book Set

Book Preface

INDIFFERENT GONAD Although sex is determined at fertilization, the gonads initially go through an indifferent stage weeks 4–7 when there are no specific ovarian or testicular characteristics. The indifferent gonads develop in a longitudinal elevation or ridge of intermediate mesoderm called the urogenital ridge. The components of the indifferent gonads are as follows: • Primordial germ cells provide a critical inductive influence on gonad development, migrating in at week 4. They arise from the lining cells in the wall of the yolk sac. • Primary sex cords are finger-like extensions of the surface epithelium which grow into the gonad that are populated by the migrating primordial germ cells. • Mesonephric (Wolffian) and the paramesonephric (Mullerian) ducts of the indifferent gonad contribute to the male and female genital tracts, respectively.

TESTIS AND OVARY The indifferent gonad develops into either the testis or ovary.
Development of the testis and male reproductive system is directed by the following: • Sry gene on the short arm of the Y chromosome, which encodes for testis-determining factor (TDF) • Testosterone, which is secreted by the Leydig cells • Müllerian-inhibiting factor (MIF), which is secreted by the Sertoli cells • Dihydrotestosterone (DHT): external genitalia Development of the ovary and female reproductive system requires estrogen. Ovarian development occurs in the absence of the Sry gene and in the presence of the WNT4 gene.

MEIOSIS Meiosis occurs within the testis and ovary. This is a specialized process of cell division that produces the male gamete (spermatogenesis) and female gamete (oogenesis). There are notable differences between spermatogenesis and oogenesis.
Meiosis consists of 2 cell divisions. In meiosis I, the following events occur: • Synapsis: pairing of 46 homologous chromosomes • Crossing over: exchange of segments of DNA • Disjunction: separation of 46 homologous chromosome pairs (no centromere-splitting) into 2 daughter cells, each containing 23 chromosome pairs In meiosis II, synapsis does not occur, nor does crossing over. Disjunction does occur with centromere-splitting

SPERMATOGENESIS At week 4, primordial germ cells arrive in the indifferent gonad and remain dormant until puberty. • When a boy reaches puberty, primordial germ cells differentiate into type A spermatogonia, which serve as stem cells throughout adult life. • Some type A spermatogonia differentiate into type B spermatogonia. • Type B spermatogonia enter meiosis I to form primary spermatocytes. • Primary spermatocytes form 2 secondary spermatocytes. • Secondary spermatocytes enter meiosis II to form 2 spermatids. • Spermatids undergo spermiogenesis, which is a series of morphological changes resulting in the mature spermatozoa.

OOGENESIS At week 4, primordial germ cells arrive in the indifferent gonad and differentiate into oogonia. Oogonia enter meiosis I to form primary oocytes. All primary oocytes are formed by month 5 of fetal life; they are arrested the first time in prophase (diplotene) of meiosis I and remain arrested until puberty. • Primary oocytes arrested in meiosis I are present at birth. • When a girl reaches puberty, during each monthly cycle a primary oocyte becomes unarrested and completes meiosis I to form a secondary oocyte and polar body. • The secondary oocyte becomes arrested the second time in metaphase of meiosis II and is ovulated. • At fertilization within the uterine tube, the secondary oocyte completes meiosis II to form a mature oocyte and polar body