Modulatory actions of activin-A and follistatin on the developmental competence of in vitro-matured bovine oocytes

The presence of activin receptors on oocytes and granulosa cells suggests that activin and its binding protein, follistatin, may regulate oocyte maturation. The aim of the present study was to investigate whether activin-A. and follistatin can influence the in vitro maturation of bovine oocytes as assessed by their competence to form blastocysts after in vitro fertilization. Bovine cumulus oocyte complexes (COCs) were cultured for 22-24 h at 38.5 degrees C in tissue culture medium-199 supplemented with 10% estrous cow serum, eCG (2.5 IU/ml), and either no treatment (control), activin-A (0.1 or 0.5 mu g/ml), follistatin (0.1, 1, or 10 mu g/ml), or activin-A (0.5 mu g/ml) in combination with follistatin (0.5 or 5 mu g/ml), In separate experiments, the same treatments were also tested on cumulus-free oocytes, which had a much reduced developmental capacity when compared to COCs. Neither activin-A nor follistatin affected the postfertilization cleavage rate of either COCs (similar to 60%) or cumulus-free oocytes (similar to 40%), Activin increased (p < 0.05) the proportion of cleaved oocytes that reached the blastocyst stage when added to both COCs (38% increase) and cumulus-free oocytes (160% increase), with the magnitude of response much greater with the latter. Follistatin had a dose-dependent inhibitory effect on blastocyst yield from COCs (67% reduction, p < 0.05) and opposed the stimulatory effect of activin (p < 0.05). With cumulus-free oocytes, however, follistatin did not further decrease the low developmental potential of oocytes. A positive correlation (r = 0.57, p < 0.001) was found between endogenous levels of activin-A produced by COCs and their postcleavage development to the blastocyst stage. No such correlation was found between endogenous follistatin level and postcleavage development (r = 0.10, p = 0.46). Endogenous levels of activin-A and follistatin secreted by cumulus-free oocytes were undetectable. These in vitro observations support the hypothesis that activin-A and follistatin, both secretory products of cumulus cells, contribute to the regulation of oocyte maturation in vivo.