Xiuliang Dai: Department of Reproductive Medicine Center, Affiliated Changzhou Maternity and Child Health Care Hospital, Nanjing Medical University, Changzhou, Jiangsu, China.
Qian Zhang: State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, China.
Zhenzhen Yu: State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, China.
Weiwei Sun: State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, China.
Rong Wang: State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, China.
Dengshun Miao: State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, China.
Previous studies have demonstrated that the polycomb repressor is universally expressed in all types of testicular cells and might regulate the spermatogonia proliferation, however, it is unclear whether plays a critical role in maintaining normal male fertility in vivo. To answer this question, we first confirmed that is universally expressed in all types of testicular cells and found that the gene relative expression levels of in testis were the highest relative to other organs. Then we investigated the role of in maintaining normal male fertility using knockout male mouse model. Our results demonstrated that deficiency resulted in totally male infertility with smaller testis, severe oligospermia and sperm malformation. Mechanistically, decreased serum testosterone levels with down-regulating 3βHSD and 17βHSD expression levels, reduced germ cell proliferation, increased germ cell apoptosis with up-regulating p16, p19, p53 and p21 expression levels, increased reactive oxygen species (ROS) and HO levels with down-regulating gene expression levels of anti-oxidant enzymes, and increased 8-OHdG and γ.H2AX positive cells in testis were observed in deficient mice compared with wild-type mice. These results indicate that deficiency results in male infertility by reducing testosterone syntheses, increasing oxidative stress and DNA damage, activating p16 and p19 signaling pathway, inhibiting germ cell proliferation and inducing germ cell apoptosis and sperm malformation. Thus, may be a novel and potential target for the clinic treatment of male infertility.
