Altered placental FoxP3 expression and exosome profile in maternal hypothyroidism.

INTRODUCTION

Maternal hypothyroidism, characterized by insufficient thyroid hormone levels during pregnancy, is linked to adverse outcomes including preeclampsia, intrauterine growth restriction, and miscarriage. Beyond supporting fetal neurodevelopment, thyroid hormones are essential for maintaining maternal immune tolerance to the semi-allogeneic fetus. Regulatory T (Treg) cells, particularly those expressing Forkhead box P3 (FoxP3), are key mediators of this tolerance. Although reduced FoxP3+ Tregs have been associated with pregnancy complications, their role in maternal hypothyroidism remains unclear. Exosomes, important mediators of immune signaling, may also influence FoxP3+ Tregs, but their function in hypothyroid placentas is poorly understood.

METHODS

Placentas from hypothyroid and healthy pregnancies were analyzed. FoxP3 and the exosome marker CD63 were evaluated by immunohistochemistry and ELISA, with FoxP3 and the trophoblast marker CK7 also assessed by immunofluorescence. Histomorphological alterations were examined using H&E staining.

RESULTS

Histomorphological analysis revealed pathological changes in hypothyroid placentas. A significant reduction in FoxP3+ cells was detected in hypothyroid placentas compared to controls, while CD63 expression showed no difference between groups. Immunofluorescence confirmed FoxP3 expression in trophoblasts.

DISCUSSION: This study is the first to demonstrate an association between maternal hypothyroidism and FoxP3 expression and suggests that a reduction in FoxP3+ cells may contribute to impaired feto-maternal immune tolerance. The detection of FoxP3 in trophoblasts provides novel insight into their potential immunomodulatory role. These findings suggest that FoxP3 may act as a mediator in the pathophysiology of maternal hypothyroidism and highlight the need for further mechanistic and clinical studies.