Endocrine Abstracts

Cumulus cells are a group of specialized granulosa cells that surrounds oocytes and are critical for female fertility. During ovulation, cumulus cells need to be expanded systematically in order to support the maturation, ovulation and fertilization of oocytes, whereas their apoptosis will result in the decline of fertilization rate and pregnancy outcome. However, the molecules as well as their signalings involved in the control of cumulus cell-oocyte complex (COC) expansion are complicated and await more studies. By analyzing several microarray and RNA-seq datasets, we intriguingly noticed that BMP8 expression in cumulus cells was positively correlated to human oocyte maturation and zygote developmental competence. Using a rat superovulation model, we found that Bmp8 transcripts were up-regulated by the luteinizing hormone signaling and were abundant in cumulus cells of pre-ovulatory follicles. Furthermore, BMP8 treatment can induce COC expansion as well as the expression of COC expansion-related genes. Hoechst-propidium iodide double staining further revealed that BMP8 can decrease cumulus cell apoptosis in ovulated COCs. BMP8 can induce the phosphorylation of both SMAD1/5/8 and SMAD2/3 in isolated COCs. Signaling dissection by inhibitors further indicated that blockage of SMAD2/3 pathway can impair BMP8-induced COC expansion, whereas blockage of either SMAD1/5/8 pathway or SMAD2/3 pathway dampens the protective role of BMP8 against cumulus cell apoptosis, indicating that both pathways are needed for BMP8-mediated cumulus cell survival. Taken together, our data demonstrated that BMP8 sustains both expansion and survival of cumulus cells through different SMAD downstreams. With these capabilities, BMP8 can contribute to the maintenance of oocyte quality and this may have clinical applications when doing in vitro fertilization.