Expression of proteins related to thyroid hormone function in the uterus is down-regulated at the day of implantation in hypothyroid pregnant rats

Cell Biol Int. 2019 May;43(5):486-494. doi: 10.1002/cbin.11114. Epub 2019 Mar 12.

Abstract

Hypothyroidism has been linked to infertility, but the mechanisms underlying infertility-related hypothyroidism have yet to be fully elucidated. Therefore, in this study, effects of hypothyroidism on expression of the proteins related to thyroid hormone function in the uterus, which were thought to play a role implantation, including thyroid hormone receptor (TR), thyroid stimulating hormone receptor (TSHR), retinoic acid receptor (RAR) and extracellular kinase (ERK) were identified. Pregnant female rats were rendered hypothyroid by giving methimazole (MMI), orally. Following hypothyroid induction, rats were grouped into control (non-treated) and received subcutaneous thyroxine at 20, 40, and 80 μg/kg/day for five consecutive days. At Day 6, which is the day of implantation (GD 6), rats were sacrificed and the number of embryo implantation site in the uterus was calculated. Then, uterine horns were harvested and expression of the above proteins and their mRNAs were identified by Western blotting and real-time PCR, respectively. In non-treated hypothyroid pregnant rats, the number of embryo implantation sites decreased as compared to euthyroid and hypothyroid rats receiving thyroxine treatment. Similarly, expression of TRα-1, TRβ-1, TSHR, ERK1/2 and RAR proteins and mRNA in the uterus of non-treated hypothyroid rats also decreased (P < 0.05 when compared to euthyroid and thyroxine-treated hypothyroid rats). In conclusion, downregulated expression of the thyroid hormone related proteins in the uterus at the day of implantation might result in infertility as reported in hypothyroid condition.

Keywords: Thyroxine; hypothyroidism; implantation; thyroid hormone related proteins; uterus.

MeSH terms

  • Animals
  • Down-Regulation / drug effects
  • Embryo Implantation
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Hypothyroidism / complications
  • Hypothyroidism / physiopathology*
  • MAP Kinase Signaling System / drug effects
  • Methimazole / pharmacology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Retinoic Acid / analysis
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / analysis
  • Receptors, Thyroid Hormone / metabolism
  • Receptors, Thyrotropin / analysis
  • Receptors, Thyrotropin / metabolism
  • Thyroid Gland / metabolism*
  • Thyroid Gland / physiology
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism*
  • Thyroid Hormones / physiology
  • Thyroxine / pharmacology
  • Uterus / metabolism
  • Uterus / physiology

Substances

  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Receptors, Thyrotropin
  • Thyroid Hormones
  • Methimazole
  • Thyroxine