title: Characterization of the testicular, epididymal and endocrine phenotypes in the Leuven Vdr-deficient mouse model: targeting estrogen signalling.
abstract: Vitamin D is a key factor for calcium and bone homeostasis, but signalling through the vitamin D receptor (VDR) seems also to be important for testicular function. To test the functional role of vitamin D signalling we examined the male reproductive system of the Leuven Vdr-ablated (Vdr(-/-)) mice, previously established as a model for hereditary vitamin D-resistant rickets. We investigated reproductive hormones, changes in gene expression and histological phenotype of eleven Vdr(-/-), eight Vdr(+/-) and nine Vdr(+/+) mice. Testicular and epididymal histology were grossly normal in Vdr(-/-) mice. Accordingly, no differences were found in serum concentrations of testosterone, estradiol, LH, and FSH or testicular expression of Cyp19a1, Ersα, Cyp17a1, Star, Insl3, Inhbb, and Amh. However, a significantly lower ERβ expression was found in testis of Vdr(+/-) and Vdr(-/-) mice, conversely epididymal expressions of ERα and the estrogen-target gene Aqp9 were higher. In conclusion, vitamin D seems dispensable for murine spermatogenesis and sex hormone production, but aberrant estrogen-signalling may elicit some of the VDR-mediated effects on male reproduction.
authors.affiliation: University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. blombergjensen@gmail.com
authors.forename: Martin
authors.initials: M
authors.lastname: Blomberg Jensen
authors.forename: Liesbet
authors.initials: L
authors.lastname: Lieben
authors.forename: John E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Ariane
authors.initials: A
authors.lastname: Willems
authors.forename: Anne
authors.initials: A
authors.lastname: Jørgensen
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.forename: Ewa
authors.initials: E
authors.lastname: Rajpert-De Meyts
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D004195:Disease Models, Animal; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D056726:Genetic Association Studies; D012739:Gonadal Steroid Hormones / Q000097:blood; D006062:Gonadotropins / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology
chemical_list: D004967:Estrogens; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D014807:Vitamin D; D001141:Aromatase
keywords: Estrogen; Fertility; Reproduction; Sex hormones; Testis; Vitamin D