GREATER THAN 99% of ovarian follicles undergo a degenerative process called atresia during reproductive life. Extending earlier morphological analysis, recent studies have demonstrated that apoptotic cell death is the molecular mechanism underlying follicle atresia. The use of DNA 3′-end-labeling methods allows quantitation and identification of internucleosomal degradation of DNA after gel fractionation as well as in situ analysis of specific cell types undergoing DNA fragmentation in histological sections. Using rats as the experimental model, gonadotropins, epidermal growth factor (EGF)/transforming growth factor-α (TGFα), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and estrogens have been identified as follicle survival factors capable of suppressing apoptotic DNA fragmentation, whereas androgens, interleukin-6 (IL-6), and GnRH are potential atretogenic factors. This review summarizes the historical background of studies on follicle atresia and selection as well as recent advances in the intraovarian hormonal mechanisms that control follicle apoptosis. It is suggested that during the penultimate stage of follicle development, exposure to a survival factor (probably FSH) is responsible for follicle selection.

Although surgical induction of cryptorchidism in the rat is known to cause infertility due to disruption of spermatogenesis, the exact cellular mechanism responsible for the degenerative changes in cryptorchid testes is unclear. Using a sensitive autoradiographic method for the detection of apoptotic DNA fragmentation, we have investigated the effect of experimentally induced cryptorchidism on apoptotic cell death in testes of immature rats. Bilateral or unilateral cryptorchidism decreased the weight of affected testes within 4 days; these decreases (24-27%) became significant (P < 0.05) at 7 days after the operation. Testes of sham-operated animals contained predominantly high molecular weight DNA (> 15 kb), whereas DNA cleavage into low molecular weight ladders characteristic of apoptosis was increased by induction of bilateral cryptorchidism in a time-dependent manner, i.e., 2.0-, 2.8-, and 4.2-fold (p < 0.05) at 2, 4, and 7 days after operation, respectively. In unilaterally cryptorchid animals, sham-operated testes also contained predominantly high molecular weight DNA, whereas induction of cryptorchidism of the contralateral testes increased DNA cleavage into low molecular weight fragments 3.0-, 2.8-, and 3.9-fold (p < 0.05) at 2, 4, and 7 days after the operation, respectively. In situ analysis of DNA fragmentation in testes of unilaterally cryptorchid rats at 7 days after the operation indicated that germ cells, mainly primary spermatocytes were affected and that the percentage of seminiferous tubules containing labeled cells increased in the operated testis as compared to the contralateral control in the same animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Polycystic ovary syndrome (PCOS) is a state of altered steroid hormone production and activity. Chronic estrogen exposure or lack of progesterone due to ovarian dysfunction can result in endometrial hyperplasia and carcinoma. A key contributor to our understanding of progesterone as a critical regulator for normal uterine function has been the elucidation of progesterone receptor (PR) expression, regulation, and signaling pathways. Several human studies indicate that PR-mediated signaling pathways in the nucleus are associated with progesterone resistance in women with PCOS. The aim of this review is to provide an overview of endometrial progesterone resistance in women with PCOS; to present the PR structure, its different isoforms, and their expression in the endometrium; to illustrate the possible regulation of PR and PR-mediated signaling in progesterone resistance in women with PCOS; and to discuss current clinical treatments for atypical endometrial hyperplasia and endometrial carcinoma in women with PCOS and accompanying progesterone resistance.