Maternal Thyroid Hormone Deficiency During Gestation and Lactation Alters Metabolic and Thyroid Programming of the Offspring in the Adult Stage

Abstract

Environmental stimuli during critical developmental stages establish long-term physiological and structural patterns that “program” health during adult life. Little is known about how alterations in hormonal supply might have consequences in metabolic and thyroid programming. This work aims to prove that alterations in the supply of thyroid hormones during gestation and lactation have long-term consequences in the metabolic and thyroid programming of the offspring. Female Wistar rats were divided into euthyroid, hypothyroid, and hypothyroid with 20 μg/day of s.c. thyroxine (T4), replacement wet nurses. Rats were mating, and after birth, pups were grouped according to their wet nurses group. Milk quality of wet nurses was assessed on days 7, 14, and 21. Body mass gain and energy intake of the offspring were monitored for 28 weeks after weaning. At sacrifice, we extracted and weighed their thyroid gland and adipose reserves, and collected blood to measure its metabolic and thyroid profiles. Hypothyroid wet nurses presented a persistent low quality of milk, while both male and female hypothyroid offspring presented lower body mass gain, higher blood glucose, dyslipidemia, hyperinsulinemia, and hyperleptinemia, as well as lower total adipose reserves, but higher visceral reserve, diminished T3 and T4 concentrations, and lower weight of thyroid gland. Thyroxine replacement prevented all changes in both wet nurses and pups. We conclude that maternal thyroid hormone deficiency during congenital and lactation stages alters the metabolic and thyroid programming of the offspring, while the reestablishment of maternal thyroid status during critical periods of development can prevent these alterations.

Thyroid Deficiency Before Birth Alters the Adipose Transcriptome to Promote Overgrowth of White Adipose Tissue and Impair Thermogenic Capacity

“…Thyroid deficiency in fetal sheep impairs adipose thermogenic capacity and the ability to maintain body temperature at birth (14). In addition, maternal hypothyroidism during pregnancy increases visceral fat mass and causes glucose intolerance in adult rat offspring (15,16).…”

Thyroxine Treatment During the Perinatal Stage Prevents the Alterations in the ObRb-STAT3 Leptin Signaling Pathway Caused by Congenital Hypothyroidism

“…There are reports that associate metabolic and thyroid programming alterations in the hypothyroid group caused by thyroid hormone deficiency during critical stages of development [12,22]. This hypothesis was probed in this research because, thyroxine treatment during pregnancy and lactation avoided the alterations caused by congenital hypothyroidism in the offspring.…”

“…Particularly, leptin modulates the insulin release, and it could participate in the insulin resistance [11]. Previously, we described that congenital hypothyroidism alters metabolic and thyroid programming [12] with a central leptin resistance [7]. The only way to avoid these fetal alterations and the presence of long-term alterations during the adult stage causing by congenital hypothyroidism is to ensure the correct thyroid hormones contribution during critical stages of development (gestation and lactation).…”

NURR1 Alterations in Perinatal Stress: A First Step towards Late-Onset Diseases? A Narrative Review

“…The hypothyroid offspring also have higher levels of blood glucose, insulin and leptin, as well as dyslipidemia [50]. These long-term anthropometric effects have also been observed in humans [49]. Maternal diet has both short-term and long-term implications on fetal and child health.…”

“…Maternal thyroid hormones are essential for normal neurodevelopment in the offspring, even after the onset of fetal thyroid function. This is particularly relevant for preterm infants who are deprived of maternal thyroid hormones following birth, who are at risk of suffering from hypothyroidism, and more likely to develop attention-deficit/hyperactivity disorder [49]. Rat models show that hypothyroid lactating females have a persistent low-quality milk, and both male and female hypothyroid offspring born of hypothyroid mothers gain less body mass with lower total adipose reserves and higher visceral reserves.…”