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Human Reproduction, Vol. 15, No. 9, 1889-1897, September 2000
© 2000 European Society of Human Reproduction and Embryology

Immunolocalization of Fas and Fas ligand in the ovaries of women with polycystic ovary syndrome: relationship to apoptosis*

Nicholas A. Cataldo,, Daniel A. Dumesic, Paul C. Goldsmith, and Robert B. Jaffe

1 Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143–0556 and 2 Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Mayo Medical Center, Rochester, MN 55905, USA 3 Present address: Buck Center for Research in Aging, Novato, CA 94948–0638, USA

Both Fas (APO-1, CD95), an apoptosis-inducing receptor, and its ligand, Fas ligand (FasL, CD95L), have been localized to the ovary. Granulosa cell apoptosis occurs in antral follicular atresia. In polycystic ovary syndrome (PCOS), antral follicles accumulate with some atretic features. The ovarian expression of Fas and FasL was examined in PCOS by immunohistochemistry and correlated with immunodetection of apoptotic cells. Fas immunostaining was present in pre-antral follicle oocytes, some primary and secondary pre-antral follicle granulosa cells, and both granulosa and theca of antral follicles. Thecal staining persisted with advancing atresia, while granulosa staining declined. In antral follicles, abundant Fas-positive cells co-localized with scattered nuclei immunopositive for apoptosis. Ovarian vascular myocytes were strongly Fas-immunopositive. FasL immunostaining was present in pre-antral follicles in oocytes and variably in granulosa. In antral follicles, granulosa and thecal FasL staining increased with advancing atresia. Normal control ovaries showed follicular Fas and FasL staining patterns similar to those in PCOS, but vascular staining was less prominent. In one healthy follicle, Fas immunostaining was seen in the oocyte and weakly in mural granulosa and theca interna. The results suggest that in PCOS, an alteration in Fas-mediated apoptosis, does not cause abnormal folliculogenesis, but may promote ovarian vascular remodelling.

Key words: apoptosis/Fas/Fas ligand/human ovary/polycystic ovary syndrome

* Presented, in part, at the 80th Annual Meeting, The Endocrine Society, New Orleans, Louisiana, June, 1998.

4 To whom correspondence should be addressed at: Department of Gynecology and Obstetrics, Stanford University Medical School, Stanford, CA 94305–5317, USA. E-mail: ncataldo{at}stanford.edu


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