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.

摘要 研究目的：明确泌乳期乳汁质量对甲状腺功能减退子代的代谢与甲状腺编程的影响。材料与方法：选取10周龄雌性Wistar大鼠，分为甲状腺功能正常（euthyroid）组与甲状腺切除术诱导的甲状腺功能减退（hypothyroidism）组。将大鼠合笼交配，子代出生1天后分为三组：甲状腺功能正常子代（euthyroid offspring, EO）、甲状腺功能减退子代（hypothyroid offspring, HO）以及由甲状腺功能正常哺乳母鼠代养的甲状腺功能减退子代（hypothyroid offspring with euthyroid wet nurse, HRO）。泌乳期间，检测乳汁质量并测量子代体长；每周记录子代体重与能量摄入情况，并分别在青春期前（P35-36）与青春期后（P55-56）检测其代谢谱。于P56日龄时处死所有实验动物，称量脂肪组织重量，解剖甲状腺组织用于组织学处理。研究结果：相较于甲状腺功能正常母鼠的乳汁，甲状腺功能减退母鼠的乳汁中蛋白质（16%~26%）、脂质（22%~29%）与乳酸（22%~37%）含量均显著降低。HO组子代的体重增长（23%~33%）、体长（11%~13%）与能量摄入（15%~21%）均低于对照组。此外，HO组子代存在空腹血糖受损与血脂异常，血清甲状腺激素水平降低18%~34%，脂肪储备减少26%~68%，甲状腺重量降低25%~34%，且甲状腺组织细胞结构出现异常。HRO组子代出现与HO组一致的代谢异常，但甲状腺功能障碍得到部分改善：其血清甲状腺激素浓度较HO组提升约10%，甲状腺重量有所恢复，但仍存在组织学腺体异常。研究结论：泌乳期将甲状腺功能减退子代交由甲状腺功能正常的哺乳母鼠代养，可改善子代的甲状腺编程，但无法改变其代谢编程。