Retinoic acid-induced CYP51 nuclear translocation promotes meiosis prophase I process and is correlated to the expression of REC8 and STAG3 in mice

Xinyi Mu; Jia Wen; Qian Chen; Zhengpin Wang; Yijing Wang; Meng Guo; Yi Yang; JinRui Xu; Zhiqing Wei; Guoliang Xia; Mengye Yang; Chao Wang

doi:10.1242/bio.035626

Retinoic acid-induced CYP51 nuclear translocation promotes meiosis prophase I process and is correlated to the expression of REC8 and STAG3 in mice

Biol Open. 2018 Nov 12;7(11):bio035626. doi: 10.1242/bio.035626.

Authors

Xinyi Mu^{1

2}, Jia Wen¹, Qian Chen¹, Zhengpin Wang¹, Yijing Wang¹, Meng Guo³, Yi Yang⁴, JinRui Xu⁴, Zhiqing Wei⁴, Guoliang Xia^{1

4}, Mengye Yang⁵, Chao Wang⁶

Affiliations

¹ State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
² Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China.
³ Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China.
⁴ Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, College of Life Science, Ningxia University, 539 W Helanshan Road, Xixia District, Yinchuan, Ningxia 750021, China.
⁵ Department of Biochemistry, College of Life Sciences, Wuhan University, Luojia Hill, Wuhan 430072, China.
⁶ State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China wangcam@126.com.

Abstract

Lanosterol 14 α-demethylase (CYP51) plays a crucial role in cholesterol biosynthesis. In gamete development, CYP51 is involved in initiating meiosis resumption in oocytes through its product, meiosis activating sterol (MAS). In this study, CYP51 was observed to localize within the nucleus of germ cells undergoing meiotic prophase I. Following the addition of retinoic acid (RA) to induce meiosis or the RA receptor pan-antagonist AGN193109 to block meiosis in fetal ovaries, the translocation of CYP51 into the nucleus of oocytes was advanced or delayed, respectively. In addition, treatment with Cyp51-siRNA or RS21745, a specific CYP51 inhibitor, significantly delayed the meiotic progression of oocytes in the ovary, with most oocytes arresting at the zygotene stage, and likewise, significantly reduced perinatal primordial follicle formation. Furthermore, inhibition of CYP51 is correlated to significantly decreased expression of REC8 and STAG3, both of which are meiosis-specific cohesin subunits. To sum up, RA-induced CYP51 nuclear translocation is critical for oocytes meiotic progression, and consequently folliculogenesis, which might act through impacting the expression of meiosis-specific cohesins REC8 and STAG3.

Keywords: CYP51; Chromosome synapsis; Meiosis; Oocytes; Primordial follicle formation.