Perfluorooctanoic acid (PFOA) has attracted widespread research attention as it is very stable, bioaccumulates, and causes reproductive toxicity. Data from several animal experiments and epidemiological studies indicate that female fertility may decline because of ovarian granulosa cell (GC) apoptosis as oocyte quality is positively associated with effective gap junctional intercellular communication (GJIC) between GCs. To the best of our knowledge, however, no previous trials have been conducted or reported on the effects of PFOA exposure on apoptosis induction in human GCs. Moreover, the roles of GJIC in GC survival and in the induction of apoptosis in GCs by PFOA remain unclear. To test this, we cultured human GCs in vitro and treated them with 0 µM, 0.3 µM, 3 µM, or 30 µM PFOA for 24 h. We also treated a human ovarian GC line (KGN) with various combinations of PFOA, retinoic acid (RA, 10 µM), and carbenoxolone disodium (CBX, 50 mM). Our findings showed that PFOA lowered human GC viability and increased apoptosis. The effects of CBX resemble those of PFOA. The combination of PFOA and CBX enhances the inhibition of GJIC by PFOA and promotes apoptosis. The effects of RA are the opposite to those of PFOA. The combination of RA and PFOA mitigates PFOA-induced GJIC inhibition and reduces apoptosis. The observed expression levels of apoptosis-related proteins were consistent with the aforementioned findings. Hence, our study demonstrated that PFOA may induce human ovarian GC apoptosis by inhibiting GJIC.

全氟辛酸（PFOA）因其非常稳定、具有生物蓄积性并引起生殖毒性而引起了广泛的研究关注。多项动物实验和流行病学研究的数据表明，女性生育能力可能因卵巢颗粒细胞（GC）凋亡而下降，因为卵母细胞质量与GC之间有效的间隙连接细胞间通讯（GJIC）呈正相关。然而，据我们所知，之前尚未进行或报告过 PFOA 暴露对人类 GC 细胞凋亡诱导的影响。此外，GJIC 在 GC 存活和 PFOA 诱导 GC 凋亡中的作用仍不清楚。为了测试这一点，我们在体外培养人 GC，并用 0 µM、0.3 µM、3 µM 或 30 µM PFOA 处理它们 24 小时。我们还用 PFOA、视黄酸（RA，10 µM）和生甲酚二钠（CBX，50 mM）的各种组合处理人卵巢 GC 系 (KGN)。我们的研究结果表明，PFOA 会降低人类 GC 的活力并增加细胞凋亡。 CBX 的作用类似于 PFOA。 PFOA与CBX联用增强PFOA对GJIC的抑制作用，促进细胞凋亡。 RA 的作用与 PFOA 相反。 RA 和 PFOA 的组合可减轻 PFOA 诱导的 GJIC 抑制并减少细胞凋亡。观察到的凋亡相关蛋白的表达水平与上述结果一致。因此，我们的研究表明PFOA可能通过抑制GJIC来诱导人卵巢GC凋亡。