Oleic acid induces down-regulation of the granulosa cell identity marker FOXL2, and up-regulation of the Sertoli cell marker SOX9 in bovine granulosa cells

During negative energy balance, the concentration of different fatty acids, especially of oleic acid (OA) increases in the follicular fluid of cattle. Previously, we showed that OA induced morphological, physiological and molecular changes in cultured bovine granulosa cells. In our present study we analyzed effects of OA on the expression of markers for granulosa and Sertoli cell identity, FOXL2 and SOX9, respectively, in addition to effects on the FOXL2 regulated genes ESR2, FST, PTGS2 and PPARG. The results showed that OA down-regulated FOXL2, ESR2, FST and PPARG but up-regulated PTGS2 and SOX9. From these data we conclude that OA can compromise granulosa cell functionality and may initiate trans-differentiation processes in bovine granulosa cells. This novel mechanism may be causally involved in postpartum fertility problems of lactating dairy cows.