Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats

New Findings

• What is the central question of this study?

  Does fetal hypothyroidism in rats alter uterine contractions and structure in the adult offspring?

• What is the main finding and its importance?

  Our study indicated that maternal hypothyroidism during pregnancy increased gestational length and decreased litter size as well as delayed puberty onset; in addition, maternal hypothyroidism caused irregular uterine contractions and histological changes in the uterus in the female offspring. This model may contribute to a better understanding of the cellular and molecular mechanisms involved in uterine contractions in fetal hypothyroidism, studies which are not possible in humans, and may help for establishing therapeutic methods for these disorders observed in uterine contractions.

Abstract

Thyroid hormones play an essential role in fetal growth. Hypothyroidism impairs reproductive function in both humans and animals. This study aims to assess the effects of fetal hypothyroidism on uterine smooth muscle contraction and structure in the adult offspring. The control group consumed tap water, while the hypothyroid group received water containing 0.025% of 6-propyl-2-thiouracial throughout gestation from mating until delivery. Isometric contractility and histological changes in uterine tissue were evaluated in female Wistar rats. We tested the effects of carbachol (10⁻¹⁰–10⁻³ M) and oxytocin (10⁻¹³–10⁻⁸ M) on uterine smooth muscle contraction in the fetal hypothyroid (FH) and control groups. Compared to controls, carbachol induced contractions with lower amplitude in the FH group (area under the curve: 1820.0 ± 250.0 vs. 1370.0 ± 125.0 arbitrary units, p < 0.001, in the control and FH groups, respectively) and frequency (86.4 ± 7.3 vs. 37.0 ± 6.1 arbitrary units, p < 0.001). Similarly after exposure to oxytocin, the amplitude (6614.0 ± 492.2 vs. 4793.0 ± 735.2 arbitrary units, p < 0.001) and frequency (367.4 ± 32.0 vs. 167.0 ± 39.0 arbitrary units, p < 0.001) of uterine contractions in the FH group were significantly lower than in the controls. In addition, the thickness of the endometrium and smooth muscle layer, and the cross-sectional area of the uterus were also significantly lower in the FH groups. Gestational length was longer and litter size was smaller in FH rats compared to controls; FH offspring also had delayed puberty. In conclusion, thyroid hormone deficiency during pregnancy increased gestational length and decreased litter size; delayed puberty onset, reduced uterine rhythmic contractions and resulted in uterine structural changes in the offspring.

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