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Published in: Reproductive Biology and Endocrinology 1/2018

Open Access 01-12-2018 | Research

Peroxiredoxin I maintains luteal function by regulating unfolded protein response

Authors: Hyo-Jin Park, Dong Gil Lee, Jung Bae Seong, Hyun-Shik Lee, Oh-Shin Kwon, Beom Sik Kang, Jeen-woo Park, Sang-Rae Lee, Dong-Seok Lee

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

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Abstract

Background

Mounting evidence shows that ROS regulation by various antioxidants is essential for the expression of enzymes involved in steroidogenesis and maintenance of progesterone production by the corpus luteum (CL). However, the underlying mechanisms of peroxiredoxin 1 (PRDX1), an antioxidant enzyme, in luteal function for progesterone production in mice have not been reported. The aim of this study was to evaluate the functional link between PRDX1 and progesterone production in the CL of Prdx1 knockout (K/O) mice in the functional stage of CL.

Methods

The expression pattern of the unfolded protein response (UPR) signaling pathways, endoplasmic reticulum (ER) stress-induced apoptosis related genes and peroxiredoxins 1 (PRDX1) were investigated by western blotting analysis in CL tissue of 10 weeks mice during functional stage of CL. The protein levels of these genes after ER-stress inducer tunicamycin (Tm), ER-stress inhibitor tauroursodeoxycholic acid (TUDCA) and ROS scavenger, N-acetylcysteine (NAC) stimulation by intraperitoneal (i.p) injection were also investigated in CL tissue of wild type (WT) mice. Finally, we examined progesterone production and UPR signaling related gene expression in CL tissue of Prdx1 K/O mice.

Results

We demonstrated that PRDX1 deficiency in the functional stage activates the UPR signaling pathways in response to ER stress-induced apoptosis. Interestingly, CL number, serum progesterone levels, and steroidogenic enzyme expression in Prdx1 K/O mice decreased significantly, compared to those in wild type mice. Levels of UPR signaling pathway markers (GRP78/BIP, P50ATF6, and phosphorylated (p)-eIF2) and ER-stress associated apoptotic factors (CHOP, p-JNK, and cleaved caspase-3) were dramatically increased in the CL tissue of Prdx1 K/O mice. In addition, administration of the NAC, reduced progesterone production and activated ER-stress-induced UPR signaling in the CL tissue obtained from the ovary of Prdx1 K/O mice. Taken together, these results indicated that reduction in serum progesterone levels and activation of ER-stress-induced UPR signaling are restored by NAC injection in the CL of Prdx1 K/O mice.

Conclusion

These observations provide the first evidence regarding the basic mechanisms connecting PRDX1 and progesterone production in the functional stage of CL.
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Metadata
Title
Peroxiredoxin I maintains luteal function by regulating unfolded protein response
Authors
Hyo-Jin Park
Dong Gil Lee
Jung Bae Seong
Hyun-Shik Lee
Oh-Shin Kwon
Beom Sik Kang
Jeen-woo Park
Sang-Rae Lee
Dong-Seok Lee
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-018-0396-0

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