Linking mitochondrial dynamics and fertility: promoting fertility by phoenixin through modulation of ovarian expression of GnRH receptor and mitochondrial dynamics proteins DRP-1 and Mfn-2

Pflugers Arch. 2022 Oct;474(10):1107-1119. doi: 10.1007/s00424-022-02739-y. Epub 2022 Aug 16.

Abstract

Obesity is linked to reproductive disorders. Novel neuropeptide phoenixin demonstrated many therapeutic actions. In this study, we aim to evaluate phoenixin's potential effect in obesity-induced infertility through modulating mitochondrial dynamics. Ninety adult female rats were divided to 4 groups: (I), fed with normal pellet diet; (II), given phoenixin; (III), fed with high-fat diet. Rats that developed obesity and infertility were divided to 2 groups: (III-A), received no further treatment; (III-B), given phoenixin. Our results showed that phoenixin treatment in obese infertile rats significantly decreased serum levels of insulin and testosterone and ovarian levels of dynamin-related protein1(Drp1),reactive oxygen species ROS, TNF-α, MDA, and caspase-3. Phoenixin treatment also significantly increased serum estrogen progesterone, LH, and FSH together with ovarian levels of GnRH receptor (GnRHR), mitofusin2(Mfn2), mitochondrial transmembrane potential (ΔΨm), and electron transport chain (ETC) complex-I significantly when compared with obese group. Ovarian histopathological changes were similarly improved by phoenixin. Our data demonstrate phoenixin's role in improving obesity-induced infertility.

Keywords: Drp1; Infertility; Mfn2; Obesity; Phoenixin.

MeSH terms

  • Animals
  • Caspase 3
  • Estrogens
  • Female
  • Fertility
  • Follicle Stimulating Hormone
  • Infertility*
  • Insulin
  • Mitochondrial Dynamics
  • Mitochondrial Proteins
  • Neuropeptides* / pharmacology
  • Obesity / complications
  • Progesterone
  • Rats
  • Reactive Oxygen Species
  • Receptors, LHRH
  • Testosterone
  • Tumor Necrosis Factor-alpha

Substances

  • Estrogens
  • Insulin
  • Mitochondrial Proteins
  • Neuropeptides
  • Reactive Oxygen Species
  • Receptors, LHRH
  • Tumor Necrosis Factor-alpha
  • Testosterone
  • Progesterone
  • Follicle Stimulating Hormone
  • Caspase 3