Effects of Vitamin D Deficiency on Proliferation and Autophagy of Ovarian and Liver Tissues in a Rat Model of Polycystic Ovary Syndrome

Biomolecules. 2019 Sep 10;9(9):471. doi: 10.3390/biom9090471.


Aim: We aimed to examine the alterations of the insulin signaling pathway, autophagy, nitrative stress and the effect of vitamin D supplementation in the liver and ovaries of vitamin D deficient hyperandrogenic rats.

Methods: Female Wistar rats received eight weeks of transdermal testosterone treatment and lived on a low vitamin D diet (D-T+). Vitamin D supplementation was achieved by oral administration of vitamin D3 (D+T+). Sham-treated (D+T-) and vitamin D deficient animals (D-T-) served as controls. (N = 10-12 per group).

Results: D-T+ animals showed decreased LC3 II levels in the liver and increased p-Akt/Akt and p-eNOS/eNOS ratios with decreased insulin receptor staining in the ovaries. Vitamin D supplementation prevented the increase of Akt phosphorylation in the ovaries. Vitamin D deficiency itself also led to decreased LC3 II levels in the liver and decreased insulin receptor staining in the ovaries. D-T+ group showed no increase in nitrotyrosine staining; however, the ovaries of D-T- rats and the liver of D+T+ animals showed increased staining intensity.

Conclusion: Vitamin D deficiency itself might lead to disrupted ovarian maturation and autophagy malfunction in the liver. Preventing Akt phosphorylation may contribute to the beneficial effect of vitamin D treatment on ovarian function in hyperandrogenism.

Keywords: autophagy; hyperandrogenism; insulin resistance; oxidative stress; polycystic ovary syndrome (PCOS); vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Liver / pathology*
  • Nitrosative Stress
  • Ovary / pathology*
  • Polycystic Ovary Syndrome / complications*
  • Polycystic Ovary Syndrome / metabolism
  • Polycystic Ovary Syndrome / pathology*
  • Rats
  • Rats, Wistar
  • Receptor, Insulin / metabolism
  • Receptors, Calcitriol / metabolism
  • Signal Transduction
  • Vitamin D Deficiency / complications*


  • Receptors, Calcitriol
  • Receptor, Insulin