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INTRODUCTION

The female reproductive system regulates the hormonal changes responsible for puberty and adult reproductive function. Normal reproductive function in women requires the dynamic integration of hormonal signals from the hypothalamus, pituitary, and ovary, resulting in repetitive cycles of follicle development, ovulation, and preparation of the endometrial lining of the uterus for implantation should conception occur. It is critical to understand pubertal development in normal girls (and boys) as a yardstick for identifying precocious and delayed puberty.

For further discussion of related topics, see the following chapters: amenorrhea and pelvic pain (Chap. 386), infertility and contraception (Chap. 389), menopause (Chap. 388), disorders of sex development (Chap. 383), and disorders of the male reproductive system (Chap. 384).

DEVELOPMENT OF THE OVARY AND EARLY FOLLICULAR GROWTH

The ovary orchestrates the development and release of a mature oocyte and secretes hormones (e.g., estrogen, progesterone, inhibins A and B, relaxin) that play critical roles in a variety of target tissues, including breast, bone, and uterus, in addition to the hypothalamus and pituitary. To achieve these functions in repeated monthly cycles, the ovary undergoes some of the most dynamic changes of any organ in the body. Primordial germ cells can be identified by the third week of gestation, and their migration to the genital ridge is complete by 6 weeks of gestation. Germ cells persist within the genital ridge, are then referred to as oogonia, and are essential for induction of ovarian development. In patients with 45,X Turner syndrome, primordial germ cells proliferate and migrate to the genital ridge, but do not persist as their survival requires the presence of pregranulosa cells that are dependent on the presence of both X chromosomes. (Chap. 383).

The germ cell population expands, and starting at ~8 weeks of gestation, oogonia begin to enter prophase of the first meiotic division and become primary oocytes. This allows the oocyte to be surrounded by a single layer of flattened granulosa cells to form a primordial follicle (Fig. 385-1). Granulosa cells are derived from mesonephric cells that invade the ovary early in its development, pushing the germ cells to the periphery. Although there is evidence that both oocyte-like cells and follicle-like structures can form from embryonic stem cells in culture, there is, as yet, no clear evidence that this occurs in vivo and thus, the ovary appears to contain a nonrenewable pool of germ cells. Through the combined processes of mitosis, meiosis, and atresia, the population of oogonia reaches its maximum of 6–7 million by 20 weeks of gestation, after which there is a progressive loss of both oogonia and primordial follicles through the process of atresia. It appears that entry into meiosis provides some degree of protection from programmed cell death. At birth, oogonia are no longer present in the ovary, and only 1–2 million germ ...

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