Hurp deficiency in mice leads to female infertility caused by an implantation defect.
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.
Tsai
Ching-Yen
CY
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Chou
Chen-Kung
CK
Yang
Chu-Wen
CW
Lai
Yi-Chen
YC
Liang
Chih-Chia
CC
Chen
Chun-Ming
CM
Tsai
Ting-Fen
TF
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
D018797:Cell Cycle Proteins; C532763:HURP protein, mouse