INVOLVEMENT OF FAS ANTIGEN IN OVARIAN FOLLICULAR ATRESIA AND LUTEOLYSIS

The Fas antigen (Fas) is a cell-surface receptor protein that mediates apoptosis-inducing signals and plays an important role in the immune system. Significant amounts of Fas mRNA can be detected not only in ly mphoid organs but also in the liver, heart, and ovary. In the ovary, a poptosis is thought to cause follicular atresia and luteolysis. We hav e investigated the involvement of Fas in these events. Here we report that Fas protein is expressed on granulosa and luteal cells but not on oocytes in the ovary. An injection of anti-fas monoclonal antibody wi th apoptosis-inducing activity into adult mice enhanced follicular atr esia and luteolysis. After the injection, the corpora lutea disappeare d and the number of follicles containing pyknotic granulosa cells incr eased. There were also fewer ovulated ova and lower levels of luteal c ell-produced progesterone. Furthermore, as the result of a non-functio nal Fas/Fas ligand system, mature ovaries from the mouse mutant lpr (l ymphopuoliferation) were histologically abnormal in terms of follicula r development, in that the number of secondary follicles significantly increased. These results suggested that Fas plays an important role i n follicular atresia and luteolysis in the ovarian physiology of adult mice. (C) 1997 Wiley-Liss, Inc.