Immunohistochemical detection and distribution of the 1,25-dihydroxyvitamin D3 receptor in rat reproductive tissues

Abstract

Vitamin D3, via its active metabolite 1,25-dihydroxyvitamin D3, plays a critical part in male and female reproduction in the rat. 1,25-Dihydroxyvitamin D3 activity is mediated by an intracellular receptor (VDR). VDR distribution in reproductive tissue has not been studied using antibodies against the receptor. We developed a polyclonal antibody against the VDR and used it to examine VDR distribution in male and female rat reproductive tissues. In rat testes, VDR epitopes were observed in seminiferous tubules, specifically in spermatogonia, Sertoli cells and spermatocytes. Spermatozoa stained faintly. Epithelial cells of the epididymis, seminal vesicles and prostate also expressed VDR epitopes. In the female rat reproductive tract, immunostaining for VDR was seen in ovarian follicles, specifically in granulosa cells. Weaker VDR immunostaining was observed in follicular thecal cells and in the ovarian stroma and germinal epithelium. Corpus luteal cells stained intensely for VDR. Epithelium of fallopian tubes and the uterus also contained VDR epitopes. Both nuclear and cytoplasmic VDR immunostaining was observed in male and female rat reproductive tissues. We conclude that the VDR is widely distributed in male and female reproductive tissues and that it is likely to mediate actions of 1,25-dihydroxyvitamin D3 in the tissues.

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

“…While these previous studies in nondonor IVF patients were mostly speculative in this regard, by using the oocyte donorrecipient model, Rudick et al [71] directly evaluated the role of the endometrium and its impact on implantation, and is consistent with the postulate that vitamin D modulates NK cell activity. In addition, VDR expression has been demonstrated in the endometrium [12] and up-regulation of HOXA10-a protein essential for embryo implantation and fertility-has been demonstrated following administration of vitamin D. Furthermore, experiments in mice have shown diminished implantation in association with reduced maternal HOXA10 expression [79]. Taken collectively, these findings strongly suggest that vitamin D signaling contributes to successful embryo implantation.…”

“…As in male rats, VDR has been isolated from the female reproductive organs-including the ovaries, fallopian tubes, and endometrium of the uterus [12]-thereby affirming its potential role as a genomic regulator of reproduction. In VDR null mice, uterine hypoplasia, impaired folliculogenesis, and infertility have been noted [62,63].…”

“…1 Synthesis of vitamin D and its effects on reproduction and pregnancy. D3 cholecalciferol, GDM gestational diabetes, PCOS polycystic ovarian syndrome, SAB spontaneous abortion, VDR vitamin D receptor reproductive tract; namely, the testis, epididymis, prostate, and seminal vesicles [11][12][13], as well as in human sperm [14,15]. Results have been mixed with respect to VDR expression and semen quality.…”

p27Kip1 Stabilization and G1 Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through Down-regulation of Cyclin E/Cyclin-dependent Kinase 2 and Skp1-Cullin-F-box Protein/Skp2 Ubiquitin Ligase

“…Therefore, the inverse correlation between sunlight exposure and OCa mortality suggests that decreased synthesis of 1,25(OH) 2 D 3 may contribute to OCa initiation and/or progression. Immunohistochemical analyses and ligand binding assays have found vitamin D receptor in rat (19) and hen (20) ovaries, indicating that the ovary is a target organ for 1,25(OH) 2 D 3 . Studies have also described vitamin D receptor expression in gynecologic neoplasms including OCa (21,22), raising the possibility that 1,25(OH) 2 D 3 or its synthetic analogs may be effective against OCa.…”

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

“…The inverse correlation between sunlight exposure and OCa mortality indicates that decreased synthesis of 1,25VD may contribute to OCa initiation and/or progression. VDR has been found in rat ovaries by immunohistochemistry (23) and in hen ovaries by ligand binding assays (24), showing that the ovary is a target organ for VD. VDR expression in gynecologic neoplasms, including OCa (25,26), has also been described, indicating that VD could be an effective agent in OCa treatment and/or chemoprevention.…”