Vitamin D Supplementation Improves Uterine Receptivity in a Rat Model of Vitamin D Deficiency: A Possible Role of HOXA-10/FKBP52 Axis

Abstract

Synchronized uterine receptivity with the time of implantation is crucial for pregnancy continuity. Vitamin D (VD) deficiency has been linked to the failure of implantation. Therefore, we tested the link between the Homeobox transcription factor-10/immunophilin FK506-binding protein 52 (HOXA-10/FKBP52) axis and the uterine receptivity in VD-deficient rats. The effect of VD supplementation at different doses was also investigated. Forty-eight pregnant rats were divided into six groups (eight/group); normal control rats fed with standard chow (control), control rats supplemented with VD (equivalent dose of 400 IU/day) (control-D400). VD-deficient group (DEF) and the three VD deficiency groups with VD supplementation were equivalent to 400, 4,000, and 10,000 IU/day (DEF-D400, DEF-D4000, and DEF-D10000, respectively). The expression levels of HOXA-10/FKBP52, progesterone level, and histological evaluation of decidualization using osteopontin (OSN) and progesterone receptor (PGR) were estimated. An assessment of the uterine contractility was conducted for all rats. This study showed the downregulation of HOXA-10/FKBP52 together with increased amplitude and frequency of the uterine contractility in the DEF group compared to control. VD dose-dependent supplementation restored progesterone/receptor competency, upregulated the expressional response of HOXA-10 and its downstream FKBP52, and improved uterine receptivity and endometrial decidualization at the time of implantation that was documented by increased area% of OSN and the number of implantation beads.

Supplementation with vitamin D improves the embryo quality in in vitro fertilization (IVF) programs, independently of the patients’ basal vitamin D status

“…This effect is achieved by binding to its VDRs receptor on the endometrium, which in turn increases the expression of the HOXA10 gene, a crucial gene involved in both placentation and implantation [ 50 , 51 ]. In a rat model, supplementation of VD positively influenced the proper endometrial priming required for successful implantation and the continuation of pregnancy by enhancing progesterone and HOXA 10 expression [ 52 ]. Indeed, after VD administration, an increase in HOXA-10 was observed together with an improvement in endometrial decidualization in a dose-dependent manner.…”

The Treatment of Complementary and Alternative Medicine on Female Infertility Caused by Endometrial Factors

“…In a cross-sectional study, the values of 25(OH)D and endometrial thickness were significantly increased in the pregnancy group after intracytoplasmic sperm injection, suggesting that 25(OH)D deficiency in women could affect endometrial thickness [ 190 ]. Ashour et al [ 191 ] supplemented vitamin D to a rat model of vitamin D deficiency and found that vitamin D improved the endometrial receptivity of rats by adjusting the expression of HOXA-10. Additionally, a systematic review has investigated the relationship between vitamin D and the success rate of embryo transfer, and found that women with more adequate vitamin D showed higher clinical pregnancy rate and that higher vitamin D levels could improve the success rate of ART [ 192 ].…”

Do Popular Diets Impact Fertility?

“…The literature on female fertility suggests that vitamin D participates in both ovarian and endometrial function by taking part in follicular development and embryo implantation processes [178,179]. Nevertheless, the correlation between vitamin D and improved reproductive parameters is still ambiguous [180][181][182][183][184].…”