title: The noncircadian function of the circadian Clock gene in the regulation of male fertility.
abstract: Mice homozygous for a dominant-negative allele of the Clock gene (Clock (Δ19/Δ19)) have slightly but significantly decreased male fertility. The molecular mechanism for this reduction in fertility is unknown. In the present study, we used a small hairpin RNA (shRNA) strategy to specifically knock down the Clock gene expression in the testes of male mice and determined its effect on male fertility. Clock knockdown led to smaller litter size, a lower in vitro fertility rate, lower blastula formation rate, and lower acrosin activity of the knockdown sperm. Locomotor activity analysis of the Clock knockdown mice revealed that Clock knockdown in testes did not alter their circadian rhythm. Taken together, these results provide the first evidence that Clock gene expression in round spermatids is essential for maintaining male reproductivity and suggest that acrosin may be a novel regulatory target of the Clock gene that would regulate the fertilization and early embryonic development to blastula. These findings may provide new clues for development of novel male contraceptive strategies.
authors.affiliation: Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Shuting
authors.initials: S
authors.lastname: Cheng
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jiang
authors.forename: Xuan
authors.initials: X
authors.lastname: He
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Wang
authors.initials: W
authors.lastname: Hou
authors.forename: Shiping
authors.initials: S
authors.lastname: Li
authors.forename: Yanyou
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005298:Fertility / Q000235:genetics* / Q000502:physiology*; D005307:Fertilization in Vitro; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D013076:Sperm Count; D013081:Sperm Motility / Q000502:physiology; D013094:Spermatozoa / Q000201:enzymology; D013737:Testis / Q000033:anatomy & histology / Q000502:physiology; D013739:Testosterone / Q000097:blood; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D013739:Testosterone; D004247:DNA; D056926:CLOCK Proteins; D017430:Prostate-Specific Antigen
keywords: Clock gene; acrosin; cumulus dispersion; male reproduction; sperm