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

Abstract

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 3β- hydroxysteroid dehydrogenase (3β-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 3β-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.

Keywords: 3β-HSD; Thyroid hormones; endometrium; methimazole; total cholesterol; triglyceride..

Fig. (1)

a. Protocol of untreated control (C) and methimazole-treated hypothyroid (H) dams. b. Picture shows a control rabbit fetus at 19 pregnancy day (GD19) and the locations where the head-rump length (blue line), and head (yellow line) and abdomen (green line) diameter measurements were done. c and d. Food intake and body weight of control (white bars; n=6) and hypothyroid (black bars; n=6) rabbits before (PD) and during pregnancy (GD). At all ages, food intake was less in hypothyroid dams, but it was significantly reduced at GD1-5 (20%) and at GD16-19 (38%). (*) P ≤ 0.05.

Fig. (2)

Morphometric characteristics of the uterus in control (C, n=6) and hypothyroid (H; n=6) rabbits. a. The mean thickness of the endometrium was similar between C and H rats, but the percentage and thickness of endometrium segments > 900 µm in H rats was greater than in controls (b and c, respectively). d. No differences between groups were found in the mean myometrium thickness. The mean cross-sectional area (CSA; e) of uterine glands, number of capillaries (f) and area covered by capillaries (g) were similar between groups. (*) P = 0.04.

Fig. (3)

Hypothyroidism increases the expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) in the pregnant uterus. a. Immunoblot showing the expression of 3β-HSD in the uterus of control (C) and hypothyroid (H) dams. b. Ponceau's Red stained membrane. c. Relative 3β-HSD expression in the uterus of C and H rabbits. Note that the 3β-HSD expression in H rabbits is 220% greater than in controls. Four animals per group were averaged. (*) P = 0.02.