Hypothyroidism modifies differentially the content of lipids and glycogen, lipid receptors, and intraepithelial lymphocytes among oviductal regions of rabbits.

Hypothyroidism affects the content of triacylglycerol (TAG), total cholesterol (TC), oxidized lipids, glycogen, and infiltration of immune cells into the ovary and uterus. This study aimed to analyze the impact of hypothyroidism on the lipid content of different regions of the oviduct. Control (n = 6) and hypothyroid (n = 6; 10 mg/kg/day of methimazole in the drinking water for 30 days) adult rabbits were used. In the fimbriae/infundibulum (FIM/INF), ampulla, (AMP), isthmus (IST), and utero-tubal junction (UTJ), the TAG and TC concentrations, presence of oxidized lipid, relative expressions of perilipin A (PLIN A), peroxisome proliferator-activated receptor γ (PPARγ), CAAT/enhancer-binding protein α (C/EBPα), and farnesoid X receptor (FXRα) were analyzed. The content of glycogen and glycans, as well as the infiltration of lymphocytes, were also quantified. In the FIM/INF, hypothyroidism reduced the content of TC, expression of C/EBPα, and presence of glycans while increased the number of intraepithelial lymphocytes. In the AMP and IST-UTJ regions, hypothyroidism increased the content of TAG, oxidized lipids, expression of PPARγ, and glycogen content but decreased the expression of PLIN-A. The FXRα expression in secretory cells of IST-UTJ was higher in the hypothyroid rabbits compared to controls. Additionally, hypothyroidism reduced the C/EBPα expression and the number of intraepithelial lymphocytes in the AMP and IST-UTJ regions, respectively. We demonstrated that the effect of hypothyroidism depends on the oviductal region, possibly associated with different physiological functions specific to each region. These alterations may be related to infertility, tubal disturbances, and ectopic pregnancy observed in hypothyroid women.

Inferring lanosterol functions in the female rabbit reproductive tract based on the immunolocalization of lanosterol 14-demethylase and farnesoid beta-receptor.

Female reproductive organs have de novo synthesis of cholesterol. Some sterol molecules, intermediaries in the cholesterol synthesis, have important paracrine/autocrine actions. Lanosterol binds to the farnesoid beta-receptor (FXRß), a molecule widely expressed in the ovaries, suggesting that it may play a role in reproduction. Up to date, we know little about lanosterol functions across female reproductive organs. We described immunolocalized lanosterol 14-demethylase (LDM or CYP51A1), responsible for catalyzing the conversion of lanosterol in cholesterol, and FXRß in the ovary, oviduct, uterus, and vagina of virgin and pregnant rabbits. In virgin rats, we found CYP51A1 and FXRß immunoreactivity was found in all ovarian follicles, epithelial cells, stroma, and Graafian follicles. Also, the epithelium and stroma, as well as the smooth muscle of the oviduct, vagina, and uterus showed CYP51A1 and FXRß immunoreactivity. In pregnant dams, we observed the presence of CYP51A1 and FXRß immunoreactivity in the corpora lutea, giant uterine cells, and trophoblastic cells. The presence of CYP51A1 and FXRß support that lanosterol participates in diverse reproductive processes, including follicular maturation, transport of gametes and zygote, implantation of blastocyst, lubrication, and contraction of the vagina, secretion of female prostate, and control of delivery mediated by pelvic muscles contraction.

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

AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.

Hypothyroidism Alters the Uterine Lipid Levels in Pregnant Rabbits and Affects the Fetal Size.

BACKGROUND: Hypothyroidism has been related to low-weight births, abortion and prematurity, which have been associated with changes in the content of glycogen and vascularization of the placenta. Since hypothyroidism can cause dyslipidemia, it may affect the lipid content in the uterus affecting the development of fetuses. OBJECTIVE: To investigate the effect of hypothyroidism on the lipid levels in serum and uterus during pregnancy and their possible association with the size of fetuses. METHOD: Adult female rabbits were grouped in control (n = 6) and hypothyroid (n = 6; treated with methimazole for 29 days before and 19 days after copulation). Food intake and body weight were daily registered. At gestational day 19 (GD19), dams were sacrificed under an overdose of anesthesia. Morphometric measures of fetuses were taken. Total cholesterol (TC), triglyceride (TAG), and glucose concentrations were quantified in blood, uterus and ovaries of dams. The expression of uterine 3ß- hydroxysteroid dehydrogenase (3ß-HSD) was quantified by Western blot. RESULTS: Hypothyroidism reduced food intake and body weight of dams, as well as promoted low abdominal diameters of fetuses. It did not induce dyslipidemia and hyperglycemia at GD19 and did not modify the content of lipids in the ovary. However, it reduced the content of TAG and TC in the uterus, which was associated with uterine hyperplasia and an increased expression of 3ß-HSD in the uterus. CONCLUSION: Hypothyroidism alters the lipid content in the uterus that might subsequently affect the energy production and lipid signaling important to fetal development.