a b s t r a c t
Ovarian follicular atresia is characterized by granulosa cell apoptosis, however, the exact
mechanism is still unclear. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase, which is
associated with apoptosis in several of cell types, but its exact role in ovarian granulosa cell
apoptosis is not clearly defined. In present study, we identified the involvement of SIRT1 in
the process of follicle degeneration, which is known as “follicular atresia”, both from in vivo
models and cell culture data. The results of immunohistochemistry showed that SIRT1 was
widely detected in non-apoptotic granulosa cells of follicles, but significantly decreased
during the process of granulosa cell apoptosis. Quantitative real-time PCR and Western
blot analysis showed that the expression levels of SIRT1 mRNA and protein were increased
(P < 0.05) during follicular atresia. In order to provide more evidences elucidating the roles
of SIRT1 during the process of follicular atresia, granulosa cells were cultured in vitro with
resveratrol which acts as a potent activator of SIRT1. Results showed that resveratrol caused
a dose-dependent increase in both SIRT1 mRNA and protein levels. Meanwhile, apoptotic
rate of granulosa cell was increased (P < 0.01) in a dose-dependent manner. Additionally,
resveratrol significantly increased the expression levels of Caspase-3 (P < 0.01) and Bax
mRNA (P < 0.01), while Bcl-2 mRNA level was significantly decreased (P < 0.01). Thus, our
results suggest that SIRT1 may play important roles in the regulation of granulosa cell
apoptosis during follicular atresia in porcine ovary.