Hyaluronic acid prevents immunosuppressive drug-induced ovarian damage via up-regulating PGRMC1 expression

Sci Rep. 2015 Jan 6:5:7647. doi: 10.1038/srep07647.

Abstract

Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Aromatase / genetics
  • Aromatase / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Estradiol / metabolism
  • Female
  • Glycosides / toxicity
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects*
  • Granulosa Cells / metabolism
  • Humans
  • Hyaluronic Acid / blood
  • Hyaluronic Acid / pharmacology*
  • Hyaluronic Acid / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Immunosuppressive Agents / toxicity*
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasms / drug therapy
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / metabolism
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / prevention & control*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • Receptors, Progesterone / antagonists & inhibitors
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism*
  • Reproduction / drug effects
  • Tripterygium / chemistry
  • Tripterygium / metabolism
  • Up-Regulation / drug effects*
  • Young Adult

Substances

  • Glycosides
  • Immunosuppressive Agents
  • Membrane Proteins
  • Pgrmc1 protein, rat
  • RNA, Small Interfering
  • Receptors, Progesterone
  • Estradiol
  • Hyaluronic Acid
  • Aromatase