Consequences of vitamin D deficiency or overdosage on follicular development and steroidogenesis in Normo and hypo calcemic mouse models

Sci Rep. 2025 Apr 24;15(1):14278. doi: 10.1038/s41598-025-99437-3.

Abstract

Vitamin D deficiency (VDD) is a widespread situation, linked to patients' dietary habits and/or geographical origins. On the other hand, hypervitaminosis D (VDO) is also a worldwide problem, mainly associated with uncontrolled self-administration. In this study, we investigated the effects of VDD and VDO on sex steroid production and ovarian histology in mice. In addition to addressing the rarely explored situation of VDO, the originality of our approach is to disconnect VDD/VDO situations from the well-known calciotrophic effect of vitamin D (VitD). Our data indicate that VDD led to a significant decrease in serum LH and FSH levels, independently of serum calcium levels. VDD was also associated with increased testosterone and reduced oestradiol levels. VDO animals showed increased LH and reduced testosterone levels. Hormonal changes in the VDO animal groups were correlated with a lower accumulation of transcripts of steroidogenic genes such as CYP11A1 and 3ß-HSD, whereas these transcripts were higher in the VDD groups. CYP19A1 transcripts were lower in VDD animals than in controls. This study highlights the complex interaction between vitamin D status, the regulation of reproductive hormones and, consequently, reproductive performance. It underlines the need for caution when oral vitamin D supplementation is chosen as a therapeutic action to boost female reproductive performance, as VDO can be as detrimental as VDD.

Keywords: Liver enzyme; Ovary; Reproduction; Sex steroids; Vitamin D deficiency; Vitamin D overdose.

MeSH terms

  • Animals
  • Aromatase / genetics
  • Aromatase / metabolism
  • Calcium* / blood
  • Disease Models, Animal
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Luteinizing Hormone / blood
  • Mice
  • Ovarian Follicle* / growth & development
  • Ovarian Follicle* / metabolism
  • Ovarian Follicle* / pathology
  • Steroids* / biosynthesis
  • Testosterone / blood
  • Vitamin D Deficiency* / blood
  • Vitamin D Deficiency* / metabolism
  • Vitamin D Deficiency* / pathology
  • Vitamin D* / administration & dosage
  • Vitamin D* / blood

Substances

  • Vitamin D
  • Calcium
  • Testosterone
  • Luteinizing Hormone
  • Estradiol
  • Aromatase
  • Steroids
  • Follicle Stimulating Hormone