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：明确哺乳阶段乳汁质量对甲状腺功能减退（hypothyroidism）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，分为两组：甲状腺功能正常（euthyroid）组与甲状腺切除造模的甲状腺功能减退组。将大鼠合笼交配后，于子代出生当日将幼鼠分为三组：甲状腺功能正常子代（EO，euthyroid offspring）、甲状腺功能减退子代（HO，hypothyroid offspring）、由甲状腺功能正常代乳母喂养的甲状腺功能减退子代（HRO，hypothyroid with a euthyroid replacement wet nurse）。哺乳期间，检测乳汁质量并测量子代体长。每周测定子代体重与能量摄入情况，并分别于青春期前（P35-36）与青春期后（P55-56）阶段检测其代谢表型。于P56日龄时处死所有动物，称量各脂肪组织重量，分离甲状腺组织进行组织学处理。

研究结果：相较于甲状腺功能正常组代乳母的乳汁，甲状腺功能减退代乳母的乳汁中蛋白质、脂质与乳酸含量分别降低16%~26%、22%~29%与22%~37%。甲状腺功能减退子代（HO）的体重增益、体长与能量摄入分别降低23%~33%、11%~13%与15%~21%。此外，HO组可见空腹血糖受损与血脂异常，同时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%，并存在甲状腺细胞结构异常。由甲状腺功能正常代乳母喂养的甲状腺功能减退子代（HRO）出现与HO组相同的代谢异常，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改变。

结论：哺乳期间将甲状腺功能减退子代更换为甲状腺功能正常代乳母，可改善其甲状腺编程，但不会改变其代谢编程。