• PMID: 26264441
• Gene Name: CLOCK
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

The circadian Clock gene regulates acrosin activity of sperm through serine protease inhibitor A3K

Cheng S, Liang X, Wang Y, Jiang Z, Liu Y, Hou W, Li S, Zhang J, Wang Z.

Our previous study found that CLOCK knockdown in the testes of male mice led to a reduced fertility, which might be associated with the lower acrosin activity. In this present study, we examined the differential expression in proteins of CLOCK knockdown sperm. Clock gene expression was knocked down in cells to confirm those differentially expressions and serine protease inhibitor SERPINA3K was identified as a potential target. The up-regulated SERPINA3K revealed an inverse relationship with Clock knockdown. Direct treatment of normal sperm with recombinant SERPINA3K protein inhibited the acrosin activity and reduced in vitro fertilization rate. The luciferase reporter gene assay showed that the down-regulated of Clock gene could activate the Serpina3k promoter, but this activation was not affected by the mutation of E-box core sequence. Co-IP demonstrated a natural interaction between SERPIAN3K and RORs (α and β). Taken together, these results demonstrated that SERPINA3K is involved in the Clock gene-mediated male fertility by regulating acrosin activity and provide the first evidence that SERPINA3K could be regulated by Clock gene via retinoic acid-related orphan receptor response elements. CI - © 2015 by the Society for Experimental Biology and Medicine. FAU - Cheng, Shuting AU - Cheng S AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. FAU - Liang, Xin AU - Liang X AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China Reproductive Medical Center of The Second Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, PR China. FAU - Wang, Yuhui AU - Wang Y AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. FAU - Jiang, Zhou AU - Jiang Z AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. FAU - Liu, Yanyou AU - Liu Y AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. FAU - Hou, Wang AU - Hou W AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. FAU - Li, Shiping AU - Li S AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. FAU - Zhang, Jing AU - Zhang J AD - Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China Department of Microbiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, PR China.