Morita Kohtaro, Tokoro Mikiko, Hatanaka Yuki, Higuchi Chika, Ikegami Haruka, Nagai Kouhei, Anzai Masayuki, Kato Hiromi, Mitani Tasuku, Taguchi Yoshitomo, Yamagata Kazuo, Hosoi Yoshihiko, Miyamoto Kei, Matsumoto Kazuya
Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan.
The Asada Institute for Reproductive Medicine, Asada Ladies Clinic, Kasugai, Aichi 486-0931, Japan.
J Reprod Dev. 2018 Apr 13;64(2):161-171. doi: 10.1262/jrd.2018-005. Epub 2018 Mar 2.
Antioxidant mechanisms to adequately moderate levels of endogenous reactive oxygen species (ROS) are important for oocytes and embryos to obtain and maintain developmental competence, respectively. Immediately after fertilization, ROS levels in zygotes are elevated but the antioxidant mechanisms during the maternal-to-zygotic transition (MZT) are not well understood. First, we identified peroxiredoxin 1 (PRDX1) and PRDX2 by proteomics analysis as two of the most abundant endogenous antioxidant enzymes eliminating hydrogen peroxide (HO). We here report the cellular localization of hyperoxidized PRDX and its involvement in the antioxidant mechanisms of freshly fertilized oocytes. Treatment of zygotes at the pronuclear stage with HO enhanced pronuclear localization of hyperoxidized PRDX in zygotes and concurrently impaired the generation of 5-hydroxymethylcytosine (5hmC) on the male genome, which is an epigenetic reprogramming event that occurs at the pronuclear stage. Thus, our results suggest that endogenous PRDX is involved in antioxidant mechanisms and epigenetic reprogramming during MZT.
抗氧化机制以适度调节内源性活性氧（ROS）水平，这对于卵母细胞和胚胎分别获得并维持发育能力而言至关重要。受精后，合子中的ROS水平会升高，但母源-合子转变（MZT）期间的抗氧化机制尚未得到充分了解。首先，我们通过蛋白质组学分析确定过氧化物酶1（PRDX1）和PRDX2是消除过氧化氢（HO）的两种最丰富的内源性抗氧化酶。我们在此报告高度氧化的PRDX的细胞定位及其在新鲜受精卵母细胞抗氧化机制中的作用。用HO处理原核期的合子会增强合子中高度氧化的PRDX的原核定位，同时损害雄性基因组上5-羟甲基胞嘧啶（5hmC）的生成，这是在原核期发生的一种表观遗传重编程事件。因此，我们的结果表明内源性PRDX参与了MZT期间的抗氧化机制和表观遗传重编程。
