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.
Highlights
Successful implantation is a result of complex molecular interactions between the hormonally primed uterus and mature blastocyst, which is necessary for pregnancy continuity (OchoaBernal and Fazleabas, 2020)
The induced Vitamin D (VD) deficiency model succeeded to reduce (p < 0.01) the serum vitamin levels compared to the control group
The progesterone level followed the fluctuation in the VD level that was observed among the deficient and treated groups
Summary
Successful implantation is a result of complex molecular interactions between the hormonally primed uterus and mature blastocyst, which is necessary for pregnancy continuity (OchoaBernal and Fazleabas, 2020). Some studies have linked vitamin D (VD) status with pregnancy loss and neonatal outcomes (Mumford et al, 2018; Fernando et al, 2020). The precise physiological function of VD during pregnancy is still unclear. This certainly extends far beyond the fetal calcium regulation and bone homeostasis that occurs quite late in gestation (Hewison, 2018). Gestational VD deficiency is becoming a growing concern. A recent evidence emphasized the vital role of VD during the implantation window (Von Websky et al, 2018), and its deficiency is associated with early miscarriage (Sharef et al, 2020)
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