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

• Published in: Thyroid (New York, N.Y.) Vol. 26; no. 3; p. 466
• Main Authors: López Navarro, Eva, Ortega, Francisco J, Francisco-Busquets, Eugènia, Sabater-Masdeu, Mònica, Álvarez-Castaño, Elena, Ricart, Wifredo, Fernández-Real, José M
• Format: Journal Article
• Language: English
• Published: United States 01.03.2016
• Subjects: Adult; Case-Control Studies; Cervix Uteri - chemistry; Cross-Sectional Studies; Female; Fertility - genetics; Fertilization in Vitro; Gene Expression Regulation; Granulosa Cells - chemistry; Humans; Infertility, Female - diagnosis; Infertility, Female - genetics; Infertility, Female - physiopathology; Infertility, Female - therapy; Oocyte Retrieval; RNA, Messenger - genetics; Thyroid Hormone Receptors alpha - genetics; Thyroid Hormone Receptors beta - genetics; Young Adult
• ISSN: 1557-9077
• DOI: 10.1089/thy.2015.0416

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. In a cross-sectional study, 31 consecutive infertile and 18 fertile women undergoing oocyte retrieval procedures were investigated. The expression of TRα1, TRα2, and TRβ was evaluated in GCs and uterine CC from infertile and fertile euthyroid women. β2 adrenergic receptor (ADRβ2) 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. In GCs, the expression of the thyroid hormone receptor TRα2, which exerts a dominant negative effect, increased with age in all women tested. TRα2 mRNA was increased in infertile versus fertile women, in parallel to decreased ADRβ2 mRNA. As expected, the expression of genes associated with fertility (i.e., GREM1 and PTGS2) was downregulated in infertile women, in parallel to decreased ADRβ2 mRNA and increased TRα2 mRNA. In uterine CCs, a positive association of ADRβ2 mRNA with TRα1:TRα2 ratio was observed. Importantly, GCs from infertile women whose oocytes did not result in pregnancy had increased expression of TRα2 (p = 0.017) and lower ADRβ2 (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 TRα2 (p = 0.033) mRNA in CCs than fertile women whose oocytes resulted in pregnancy. The expression of different markers of intracellular thyroid function is linked to fertility status.