Thyroid Hormone Receptors Are Differentially Expressed in Granulosa and Cervical Cells of Infertile Women

Background: Thyroid hormones are known to exert an important role in reproduction. The objective of this study was to evaluate the expression of thyroid hormone receptors (TR) in granulosa (GC) and cervical cells (CC) of infertile euthyroid women. Methods: In a cross-sectional study, 31 consecutive infertile and 18 fertile women undergoing oocyte retrieval procedures were investigated. The expression of TR1, TR2, and TR was evaluated in GCs and uterine CC from infertile and fertile euthyroid women. 2 adrenergic receptor (ADR2) mRNA levels and the expression of genes linked to fertility such as gremlin-1 (GREM1), hyaluronan synthase 2 (HAS2), and prostaglandin-endoperoxide synthase 2 (PTGS2) were also evaluated. Results: In GCs, the expression of the thyroid hormone receptor TR2, which exerts a dominant negative effect, increased with age in all women tested. TR2 mRNA was increased in infertile versus fertile women, in parallel to decreased ADR2 mRNA. As expected, the expression of genes associated with fertility (i.e., GREM1 and PTGS2) was downregulated in infertile women, in parallel to decreased ADR2 mRNA and increased TR2 mRNA. In uterine CCs, a positive association of ADR2 mRNA with TR1:TR2 ratio was observed. Importantly, GCs from infertile women whose oocytes did not result in pregnancy had increased expression of TR2 (p=0.017) and lower ADR2 (p=0.008), GREM1 (p=0.003), and PTGS2 (p=0.002) mRNAs than fertile women whose oocytes resulted in pregnancy. Infertile women also showed more TR2 (p=0.033) mRNA in CCs than fertile women whose oocytes resulted in pregnancy. Conclusions: The expression of different markers of intracellular thyroid function is linked to fertility status.