title: Hurp deficiency in mice leads to female infertility caused by an implantation defect.
abstract: First revealed in cancer studies, HURP (hepatoma up-regulated protein) is a cell cycle-associated gene with elevated expression in the G(2)/M phase. Cell culture studies have revealed that HURP is an essential factor required for spindle formation and chromosome congression during mitosis. However, the function of HURP in an in vivo context has not been explored. We generated a Hurp knock-out (Hurp(-/-)) mouse to investigate the role of HURP in development under normal physiological conditions. Hurp(-/-) mice develop normally and are indistinguishable from their wild-type littermates. Interestingly, breeding experiments revealed that Hurp(-/-) females are completely infertile, whereas the males reproduce normally. Ovulation, fertilization, and pre-implantation embryo development are normal; however, the Hurp(-/-) females are unable to form implantation sites due to an inability to undergo the decidual reaction. This is caused by a defect in endometrial stromal proliferation that leads to implantation failure. Additionally, HURP expression in the uterus coincides with the implantation stage and can be induced by estrogen treatment. Our results demonstrate for the first time that HURP affects endometrial stromal proliferation during implantation but is dispensable during normal development in mice; specifically, HURP has an essential function in uterine biology.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Tsai
authors.forename: Chen-Kung
authors.initials: CK
authors.lastname: Chou
authors.forename: Chu-Wen
authors.initials: CW
authors.lastname: Yang
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lai
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Liang
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Ting-Fen
authors.initials: TF
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D010064:Embryo Implantation / Q000235:genetics; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005306:Fertilization / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D007247:Infertility, Female / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010060:Ovulation / Q000235:genetics; D011247:Pregnancy; D012727:Sex Characteristics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; C532763:HURP protein, mouse