Thyroid-reproductive axis interplay: immunological mechanisms and implications for female reproductive health

TL;DR

This paper explores how thyroid dysfunction affects female reproductive health through immune mechanisms, especially during pregnancy.

Contribution

The paper introduces a new framework linking thyroid dysfunction to reproductive issues via immune modulation and angiogenic factors.

Findings

Thyroid hormones regulate the hypothalamic-pituitary-gonadal axis through metabolic mediators like prolactin and leptin.

Inflammatory cytokines disrupt thyroid hormone production, linking immune activation to reproductive problems.

Thyroid dysfunction alters angiogenic factors and immune cell profiles at the maternal-fetal interface, affecting placental development.

Abstract

Thyroid dysfunction is a common endocrine disease among women of childbearing age, which seriously affects reproductive health. From an immunological perspective, this in-depth analysis clarifies the complex relationship between thyroid function and female reproduction. We studied the hypothalamic-pituitary-gonadal axis regulation by thyroid hormones through direct and indirect mechanisms, including metabolic mediators such as prolactin and leptin. Recent studies have shown that inflammatory cytokines (IL-1α, IL-1β, IL-6, IFN-γ, and TNF-α) severely disrupt the production pathways of thyroid hormones, establishing an essential link between immune activation and reproductive problems. Since the placenta serves as an active immune interface affected by thyroid activity, there are significant physiological obstacles (including increased iodine clearance and elevated deiodinase activity), immunological challenges (such as altered cytokine profiles), and pathological barriers to optimal thyroid adaptation during pregnancy. This literature review indicates that thyroid problems substantially affect reproductive outcomes by altering the immune response at the maternal-fetal interface, influencing placental development, trophoblast invasion, and vascular remodeling. This review addresses a notable research deficiency through a modern perspective on thyroid dysfunction and reproductive issues, especially inflammatory cytokines related to preeclampsia. We believe that thyroid dysfunction can alter the expression of specific angiogenic factors (including sFlt-1, PlGF, and VEGF) and modify the immune cell profile at the maternal-fetal interface (particularly NK cells, macrophages, and T regulatory cells), creating a new framework for understanding and addressing thyroid-related reproductive diseases through targeted immunomodulatory strategies.

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