Abstract
Vitamin D3 (VD3) plays an important role in the ovary and its deficiency is associated with ovarian pathologies, including polycystic ovary syndrome (PCOS). However, there is no data related to VD3 metabolism in the ovary during PCOS. Herein, we investigated differences in the expression of VD3 receptor (VDR) and key VD3 metabolic enzymes, 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1), in the ovary and periovarian adipose tissue (POAT) of control (proestrus and diestrus) and PCOS induced by letrozole rats. Vdr, Cyp27b1 and Cyp24a1 mRNA expression was determined, their protein abundance was examined and immunolocalized. Furthermore, VD3 metabolite concentrations in plasma (25OHD) and tissues (ovary and POAT; 1,25(OH)2D3), and plasma calcium level were determined. 25OHD concentration decreased markedly in letrozole-treated rats in comparison with controls, whereas calcium concentration did not vary among the examined groups. The amount of 1,25(OH)2D3 decreased in both ovary and POAT of PCOS rats. In the ovary, we found decreased Cyp27b1 and increased Vdr mRNA expression in letrozole-treated and diestrus control group. Corresponding protein abundances were down-regulated and up-regulated, respectively but only following letrozole treatment. In POAT, only Cyp27b1 transcript level and CYP27B1 protein abundance were decreased in letrozole-treated rats. VDR was immunolocalized in healthy and cystic follicles, while CYP27B1 and CYP24A1 were found exclusively in healthy ones. Concluding, our results provide the first evidence of disrupted VD3 metabolism in the ovary and POAT of PCOS rats. The reduced 1,25(OH)2D3 concentration in those tissues suggests their contribution to VD3 deficiency observed in PCOS and might implicate in PCOS pathogenesis.
Highlights
It is widely accepted that vitamin D3 (VD3) regulates calcium and phosphorus homeostasis to ensure bone health (DeLuca 2004)
A growing body of evidence highlights that VD3 plays an important role in the ovary and its deficiency is linked with several ovarian pathologies such as polycystic ovarian syndrome (PCOS)
Keeping in mind the expression of CYP27B1 responsible for active VD3 synthesis and VD3 receptor (VDR) in ovarian tissue, the question arises whether VD3 metabolism at the ovarian level is disrupted in PCOS
Summary
It is widely accepted that vitamin D3 (VD3) regulates calcium and phosphorus homeostasis to ensure bone health (DeLuca 2004). Due to the broad distribution of VD3 receptor (VDR) in the organism, V D3 effects extend to various tissues, including female reproductive organs. Both 1,25(OH)2D3 and 2 5OHD3 are inactivated by a mitochondrial 24-hydroxylase (CYP24A1) (Bikle 2014). The ovary has been identified as an extrarenal site of CYP27B1 expression and VDR is abundant in ovarian cells, suggesting local V D3 metabolism and action within the mammalian ovary (Herian et al 2018; Xu et al 2018). In details, VD3 was shown to increase the synthesis of anti-Müllerian hormone (AMH), maintaining the ovarian reserve (Irani and Merhi 2014). Hypovitaminosis D 3 has been linked to several ovarian pathologies such as PCOS (He et al 2015)
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