Oocyte-secreted factor TGFB2 enables mouse cumulus cell expansion in vitro

Cumulus expansion is necessary for the release of a fertilizable oocyte from the ovary, which is critical for the normal fertilization of mammals. Cumulus expansion requires cooperation between epidermal growth factor (EGF)-like growth factors and oocyte paracrine factors. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are well-known paracrine factors secreted by oocytes. In addition, transforming growth factor-β2 (TGFB2) was primarily expressed in oocytes and its membrane receptors type 1 receptor (TGFBR1) and type 2 receptor (TGFBR2) were located in cumulus cells. In our present study, TGFB2 induced expansion of oocytectomized (OOX) complexes and increased the expression of expansion-related genes in the presence of EGF, suggesting that TGFB2 enables cumulus expansion. Inhibition of TGF-β signaling with SD208 blocked TGFB2-promoted cumulus expansion. Furthermore, in the culture of OOX complexes from mice of Tgfbr2-specific depletion in granulosa cells, TGFB2-promoted cumulus expansion and the expression of expansion-related genes were impaired. These results suggest that TGFB2 could induce cumulus expansion through TGFBR-SMAD2/3 signaling. Tgfb2-specific depletion in oocytes using Zp3-Cre mice had no effect on cumulus expansion in vivo, possibly due to the compensatory effect of other cumulus expansion-enabling factors. Taken together, TGFB2 is involved in expansion-related gene expression and consequent cumulus expansion.