Hyperthyroidism keeps immunoglobulin levels but reduces milk fat and CD11b/c⁺ cells on early lactation

Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T₄ (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRβ1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45⁺ and CD3⁺ cells and decreased CD11b/c⁺ cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health.