Testosterone Reduces Tight Junction Complexity and Down-regulates Expression of Claudin-4 and Occludin in the Endometrium in Ovariectomized, Sex-steroid Replacement Rats

In Vivo. 2020 Jan-Feb;34(1):225-231. doi: 10.21873/invivo.11764.

Abstract

Background/aim: It was hypothesized that endometrial tight junction morphology and expression of tight junction proteins i.e., claudin-4 and occludin in the uterus, are affected by testosterone. Therefore, the effects of testosterone on these parameters in the uterus during receptivity period were investigated.

Materials and methods: Ovariectomized adult female rats were given testosterone (1 mg/kg/day) alone or in combination with flutamide or finasteride between days 6 to 8 of sex-steroid replacement treatment, which was considered the period of uterine receptivity. Ultramorphology of tight junctions was visualized by transmission electron microscopy while distribution and expression of claudin-4 and occludin were examined by immunofluorescence and real-time polymerase chain reaction respectively.

Results: Administration of testosterone caused loss of tight junction complexity and down-regulated expression of claudin-4 and occludin in the uterus.

Conclusion: Decreased endometrial tight junction complexity and expression of claudin-4 and occludin in the uterus during receptivity period by testosterone may interfere with embryo attachment and subsequent implantation.

Keywords: Testosterone; claudin-4; occludin; tight junction; uterus.

MeSH terms

  • Androgens / pharmacology
  • Animals
  • Claudin-4 / genetics
  • Claudin-4 / metabolism*
  • Endometrium / drug effects
  • Endometrium / physiology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Gonadal Steroid Hormones / metabolism
  • Occludin / genetics
  • Occludin / metabolism*
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / pharmacology*
  • Tight Junctions / drug effects
  • Tight Junctions / physiology*

Substances

  • Androgens
  • Claudin-4
  • Gonadal Steroid Hormones
  • Occludin
  • Ocln protein, rat
  • Testosterone