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Hypothyroidism induces uterine hyperplasia and inflammation related to sex hormone receptors expression in virgin rabbits

Rodríguez-Castelán, Julia, Del Moral-Morales, Aylin, Piña-Medina, Ana Gabriela, Zepeda-Pérez, Dafne, Castillo-Romano, Marlenne, Méndez-Tepepa, Maribel, Espindola-Lozano, Marlen, Camacho-Arroyo, Ignacio, Cuevas-Romero, Estela
Life sciences 2019 v.230 pp. 111-120
Western blotting, adults, cholesterol, endometrium, estrogen receptors, female fertility, females, histology, hyperplasia, hypothyroidism, inflammation, lipid content, macrophages, malondialdehyde, myometrium, progesterone receptors, rabbits, reverse transcriptase polymerase chain reaction, steroid hormones, thyroid hormone receptors, triacylglycerols, vascular endothelial growth factor A, women
In women, uterine alterations have been associated with sex steroid hormones. Sex hormones regulate the expression of thyroid hormone receptors (TRs) in the uterus, but an inverse link is unknown. We analyzed the impact of hypothyroidism on histological characteristics, vascular endothelial growth factor (VEGF-A), progesterone receptors (PR), estrogen receptors (ER), thyroid hormone receptors (TRs), perilipin (PLIN-A), and lipid content in the uterus of virgin rabbits.Twelve Chinchilla-breed adult female rabbits were grouped into control (n = 6) and hypothyroid (n = 6; 0.02% of methimazole for 30 days). The thickness of endometrium and myometrium, number of uterine glands, and infiltration of immune cells were analyzed. The expression of VEGF-A, PR, ERα, and PLIN-A was determined by RT-PCR and western blot. The uterine content of triglycerides (TAG), total cholesterol (TC), and malondialdehyde (MDA) was quantified.Hypothyroidism promoted uterine hyperplasia and a high infiltration of immune cells into the endometrium, including macrophages CD163+. It also increased the expression of VEGF-A, TRA, and ERα-66 but reduced that of PR and ERα-46. The uterine content of PLIN-A, TAG, and TC was reduced, but that of MDA was augmented in hypothyroid rabbits.Our results suggest that uterine hyperplasia and inflammation promoted by hypothyroidism should be related to changes in the VEGF-A, PR, ER, and TRs expression, as well as to modifications in the PLIN-A expression, lipid content, and oxidative status. These results suggest that hypothyroidism should affect the fertility of females.