LAUSR

Abstract Luteal regression is a natural and necessary event to regulate the reproductive process in all mammals. Prostaglandin F2&agr; (PGF2&agr;) is the main factor that causes functional and structural regression of the corpus luteum (CL). It is well known that PGF2&agr;‐mediated ROS generation is closely involved in luteal regression. Peroxiredoxin 2 (Prx2) as an antioxidant enzyme plays a protective role against oxidative stress‐induced cell death. However, the effect of Prx2 on PGF2&agr;‐induced luteal regression has not been reported. Here, we investigated the role of Prx2 in functional and structural CL regression induced by PGF2&agr;‐mediated ROS using Prx2‐deficient (‐/‐) mice. We found that PGF2&agr;‐induced ROS generation was significantly higher in Prx2‐/‐ MEF cells compared with that in wild‐type (WT) cells, which induced apoptosis by activating JNK‐mediated apoptotic signaling pathway. Also, PGF2&agr; treatment in the CL derived from Prx2‐/‐ mice promoted the reduction of steroidogenic enzyme expression and the activation of JNK and caspase3. Compared to WT mice, serum progesterone levels and luteal expression of steroidogenic enzymes decreased more rapidly whereas JNK and caspase3 activations were significantly increased in Prx2‐/‐ mice injected with PGF2&agr;. However, the impaired steroidogenesis and PGF2&agr;‐induced JNK‐dependent apoptosis were rescued by the addition of the antioxidant N‐acetyl‐L‐cysteine (NAC). This is the first study to demonstrate that Prx2 deficiency ultimately accelerated the PGF2&agr;‐induced luteal regression through activation of the ROS‐dependent JNK pathway. These findings suggest that Prx2 plays a crucial role in preventing accelerated luteal regression via inhibition of the ROS/JNK pathway. Graphical abstract Figure. No Caption available. HighlightsPrx2 deficiency in mice enhances ROS production when stimulated with PGF2&agr;.PGF2&agr; treatment in Prx2‐/‐ mice leads to impaired steroidogenesis and apoptosis.CL regression by PGF2&agr; was enhanced via ROS‐induced JNK activation in Prx2 ‐/‐ mice.Prx2 deficiency ultimately results in accelerated the PGF2&agr;‐induced luteal regression.