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Ovarian development and failure (menopause) in normal women

Corrine K Welt, MD
Section Editors
Robert L Barbieri, MD
William F Crowley, Jr, MD
Deputy Editor
Kathryn A Martin, MD


This topic will review the basic aspects of ovarian development and the pathogenesis and epidemiology of menopause. The clinical manifestations, diagnosis, and management of menopause are reviewed separately. (See "Clinical manifestations and diagnosis of menopause" and "Treatment of menopausal symptoms with hormone therapy".)


There are three main steps in ovarian development: germ cell differentiation, continuous follicular growth, and continuous follicular atresia.

Germ cell differentiation — One of the first events of sexual differentiation, occurring as early as the two-cell stage of the zygote, is the random, nearly complete inactivation of one X chromosome in all female somatic cells [1] but not germ cells [2]. Thus, somatic cells have only a few active X chromosome genes, whereas germ cells have two complete X chromosomes [2].

The primordial undifferentiated germ cells then migrate during the fourth to eighth weeks of gestation from the yolk sac to the gonadal ridge, where they are required for development of the ovaries [3]. In the absence of a testicular differentiation factor from the Y chromosome, which directs the production of müllerian-inhibiting substance (MIS) by four to six weeks gestation in males [4], the germ cells differentiate into primitive oogonia, which begin mitosis at approximately six weeks. (See "Normal sexual development".)

A quantitative morphologic study of germ cells in 17 normal human fetuses revealed a maximum of seven million germ cells five months after conception [3]; this small study remains the basis of most of our current understanding of oogenesis in humans. The first meiotic division is initiated at approximately 15 weeks, signaling the transformation of oogonia to oocytes. This meiotic division is then arrested at the first prophase until primordial follicles are formed. Medullary structures infiltrate the ovarian cortex and surround the oocytes to invest each one with a single layer of primordial granulosa cells at approximately 20 weeks of gestation, thereby beginning the formation of primordial follicles.

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Literature review current through: Nov 2017. | This topic last updated: Sep 11, 2017.
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