Hypothyroid offspring replacement with euthyroid wet nurses during lactation improves thyroid programming without modifying metabolic programming

Abstract

Objective: Determine the milk quality effect during lactation on the metabolic and thyroid programming of hypothyroid offspring. Materials and methods: Ten-week-old female Wistar rats were divided into two groups: euthyroid and thyroidectomy-caused hypothyroidism. The rats were matted and, one day after birth, the pups were divided into three groups: euthyroid offspring (EO), hypothyroid offspring (HO) and hypothyroid with a euthyroid replacement wet nurse (HRO). During lactation, the milk quality and offspring body length were evaluated. The body weight and energy intake were determined on a weekly basis, as well as the metabolic profile at the prepubertal (P35-36) and postpubertal (P55-56) ages. At P56, the animals were sacrificed, the adipose tissues were weighed and the thyroid glands were dissected for histological processing. Results: The milk of the hypothyroid wet nurse decreases proteins (16-26%), lipids (22-29%) and lactate (22-37%) with respect to euthyroid. The HO has a lower body weight gain (23-33%), length (11-13%) and energy intake (15-21%). In addition, HO presents impaired fasting glucose and dyslipidemia, as well as a reduction in seric thyroid hormone (18-34%), adipose reserves (26-68%) and thyroid gland weight (25-34%). The HO present thyroid gland cytoarchitecture alteration. The HRO develop the same metabolic alterations as the HO. However, the thyroid gland dysfunction was partially prevented because the HRO improved under about 10% of the serum thyroid hormone concentration, the thyroid gland weight although histological glandular changes presented. Conclusions: The replacement of hypothyroid offspring with a euthyroid wet nurse during lactation can improve the thyroid programming without modifying metabolic programming.

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.…”

“…This situation produces a series of cellular, molecular, and biochemical alterations that cause changes in the physiology of the tissues in adulthood [23]. For example, the hypothyroid animals had hyperleptinemia to compare with the euthyroid animals, as well as the thyroid gland malprogramming characterized by low levels of T 3 and T 4 , with structural changes in the thyroid follicles [22].…”

“…For example, congenital hypothyroidism caused a decrease in GLUT2 and glucokinase expression in liver and pancreatic islets in adulthood [26]. Besides, the thyroid gland programming does not improve when a hormonal reestablishment happens with euthyroid maternal milk during lactation [22]. Thus, the thyroxine treatment during pregnancy and lactation in hypothyroid mothers maintain the thyroid status and the proper fetal programming [27].…”

The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus

“…Hypothyroidism was induced surgically by a thyroidectomy with parathyroid reimplantation in the hypothyroid group as previously described ( 12 , 13 , 14 , 17 ). Seven days post-surgery, three females were placed with one male for mating.…”

“…In humans, some meta-analyses reveal an association between hypothyroidism, obesity, and dyslipidemia; however, it is necessary for more studies because multifactorial situations distort the association between the variables (8,9,10,11). On the other hand, previously in animal models, we reported the increased risk to develop T2D in congenital hypothyroid rats because they develop metabolic syndrome even when they are fed with a standard-balanced diet (12,13,14). The mentioned studies reveal that congenital hypothyroidism modifies the metabolic programming promoting dyslipidemia and hyperleptinemia with a change in the thyroid gland's function (12,15).…”