Bioscientifica Proceedings

Oocytes secrete factors that control cumulus and granulosa functions, including cumulus expansion and steroid hormone production. Some members of the transforming growth factor ß (TGFß) superfamily influence these activities, yet it is still not determined conclusively whether any of these superfamily members are the previously reported oocyte-secreted factors. The aim of this study was to examine the effects of TGFß1 and growth differentiation factor 9 (GDF-9) on cumulus expansion and progesterone production by mouse oocytectomized (OOX) complexes in culture. TGFß1 mimics the effects of oocytes by both enabling cumulus expansion and inhibiting progesterone production; however, neutralizing antibodies to TGFß1 in cultures of cumulus-oocyte complexes (COCs) or in co-cultures of OOX complexes failed to inhibit the ability of oocytes to enable cumulus expansion or inhibit progesterone production. Activin A had no effect on progesterone production by OOX complexes. In experiments using oocytes obtained from mice with deficient expression of GDF-9, OOX complexes cultured in the presence of heterozygous oocytes were capable of full expansion, whereas OOX complexes cultured with oocytes from GDF-9 null mice did not expand. Similarly, GDF-9 null oocytes failed to suppress FSH-induced progesterone production by OOX complexes. These results support the hypothesis that GDF-9 is the cumulus expansion enabling factor produced by mouse oocytes and that GDF-9 also inhibits cumulus progesterone production; however, the possibility remains that loss of GDF-9 may indirectly affect the ability of oocytes to produce the factors that regulate cumulus cell activity.

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