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Free Radic Biol Med. 2017 Jul;108:44-55. doi: 10.1016/j.freeradbiomed.2017.03.013. Epub 2017 Mar 18.

Peroxiredoxin 2 regulates PGF2α-induced corpus luteum regression in mice by inhibiting ROS-dependent JNK activation.

Author information

1
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; Renal Division, School of medicine, Washington University in St Louis, MO, USA.
2
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
3
Embryology Laboratory, Neway Fertility, 115 East 57th Street Suite 500, New York, NY 10022, USA.
4
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungcheongbuk-do, Republic of Korea.
5
Animal Biotechnology Division, National Institute of Animal Science, Jeollabuk-do, Republic of Korea.
6
Cancer Research Institute and Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
7
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea. Electronic address: lee1@knu.ac.kr.

Abstract

Luteal regression is a natural and necessary event to regulate the reproductive process in all mammals. Prostaglandin F2α (PGF2α) is the main factor that causes functional and structural regression of the corpus luteum (CL). It is well known that PGF2α-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 PGF2α-induced luteal regression has not been reported. Here, we investigated the role of Prx2 in functional and structural CL regression induced by PGF2α-mediated ROS using Prx2-deficient (-/-) mice. We found that PGF2α-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, PGF2α 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 PGF2α. However, the impaired steroidogenesis and PGF2α-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 PGF2α-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.

KEYWORDS:

Corpus luteum regression; Peroxiredoxin2; Prostaglandin F2α; Reactive oxygen species

[Indexed for MEDLINE]

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