The regulation of high insulin levels on ovary apoptosis in early pregnant mice

Biochem Biophys Res Commun. 2017 Jan 29;483(1):786-792. doi: 10.1016/j.bbrc.2016.12.041. Epub 2016 Dec 9.

Abstract

Studies have shown that metabolic syndrome is associated with reproductive problems. Women with metabolic syndrome, characterized by hyperinsulinemia, have common ovarian dysfunction, but the mechanism remains elusive. The aim of this research is to explore the effects of high levels of insulin on ovary function during early pregnancy. Mice in the high insulin-exposed group were given a subcutaneous injection of human recombinant insulin. After insulin treatment, changes in various hormones were tested using ELISA kits which showed hormones secreted by the ovary were significantly altered in the insulin group. TUNEL staining showed less TUNEL-positive cells in the insulin group. A significant decrease in Bax and an increase in Bcl2 in the ovary were found in the insulin group by immunohistochemical studies. Western blotting showed the expressions of apoptosis related proteins in the ovaries from the insulin group were obviously altered. In addition, expression of p-Akt proteins in the ovaries from the insulin group was significantly upregulated. Moreover, the Akt inhibitor LY294002 reversed the anti-apoptotic effects of high insulin in the ovary tissues in early pregnancy mice. All of these results showed that insulin impaired ovarian function during early pregnancy and ovarian apoptosis is imbalanced under the role of insulin. The PI3K/AKT signalling pathway might participate in this process.

Keywords: Apoptosis; Decidualization; Hyperinsulinemia; Insulin; Ovary.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • Chromones / pharmacology
  • Estradiol / metabolism
  • Female
  • Hyperinsulinism / physiopathology*
  • Insulin / administration & dosage
  • Insulin / blood*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morpholines / pharmacology
  • Ovary / metabolism*
  • Ovary / physiopathology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Pregnancy
  • Progesterone / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Chromones
  • Insulin
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Progesterone
  • Estradiol