Abstract
Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female vdr-knockout mice; however, whether VDR polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that VDR polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the TaqI, BsmI, and FokI VDR polymorphisms and ovarian responses in women undergoing COS. In this study, we recruited a control group (n = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS (n = 70). TaqI, BsmI, and FokI genotyping was performed via restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records. There were no significant differences in the genotype frequencies of VDR polymorphisms (TaqI, BsmI and FokI) between the control and COS groups. However, the allele frequency of TaqI (C allele) was significantly lower in the COS group than in the control group (p = 0.02). Follicle number but not oocyte number was lower in patients with TaqI polymorphic (TC/CC) genotypes (p = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC TaqI genotypes (p < 0.02). We identified an association between the VDR TaqI polymorphism and reduced follicle number in women undergoing COS, suggesting that VDR signaling affects the ovarian response to stimulation via unknown mechanisms.
Highlights
Calcitriol, or 1,25-hydroxycholecalciferol (1,25(OH)2D), is the active form of vitamin D, a steroid hormone that exerts classical functions in calcium and phosphorus homeostasis and bone mineralization [1]
To determine whether the presence of polymorphisms in the vitamin D receptor (VDR) gene affected the ovarian response of women undergoing Controlled ovarian stimulation (COS), we extracted clinical data from control volunteers who had declared a history of natural conception and from women who underwent the COS protocol and intracytoplasmic sperm injection (ICSI) treatment
This work provides the first demonstration of an association between the VDR TaqI polymorphic C allele frequency and decreased follicle production by women exhibiting different causes of infertility
Summary
Calcitriol, or 1,25-hydroxycholecalciferol (1,25(OH)2D), is the active form of vitamin D, a steroid hormone that exerts classical functions in calcium and phosphorus homeostasis and bone mineralization [1]. VDR expression has been reported in different central (hypothalamus and hypophysis) and peripheral reproductive organs (ovary, uterus, placenta, and oviduct) [13, 15, 16]. Evidence linking calcitriol and reproductive function has been demonstrated in 7-week-old female vdr-knockout mice. These animals exhibited uterine hypoplasia, defective folliculogenesis (the absence of mature follicles), and associated infertility [6, 7]. Female vdr-knockout mice exhibited decreased aromatase expression and activity in the ovary, and these effects were associated with elevated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations, indicating a peripheral rather than a central defect [8] and suggesting a role for calcitriol in regulating folliculogenesis
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