title: Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.
abstract: Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice.
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. liuy_p@sina.com.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. sxyasxy@163.com.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Su
authors.affiliation: The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. haojcq@yahoo.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. chenmaoxin1989@163.com.
authors.forename: Maoxin
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. weijliu@163.com.
authors.forename: Weijia
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. liaoxg@126.com.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Liao
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. lg168sn@yahoo.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D005260:Female; D005298:Fertility; D007987:Gonadotropin-Releasing Hormone / Q000032:analysis / Q000097:blood; D007248:Infertility, Male / Q000097:blood / Q000235:genetics* / Q000473:pathology; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D007986:Luteinizing Hormone / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size; D011257:Pregnancy Proteins / Q000235:genetics*; D012098:Reproduction; D013076:Sperm Count; D013737:Testis / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D013739:Testosterone / Q000032:analysis / Q000097:blood; D015854:Up-Regulation
chemical_list: C057074:Plfr protein, mouse; D011257:Pregnancy Proteins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone
keywords: Leydig cells; Plr7d1; male reproductive dysfunction