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Maternal hypothyroidism and diabetes alter plasma concentration and placental signaling of sex steroids in rats

Year: 2026

Type: article

Abstract: INTRODUCTION: Proper hormonal signaling at the maternal-fetal interface and adequate placental steroidogenesis are crucial for a successful pregnancy. However, the effects of maternal diabetes (MD) and hypothyroidism (MH) on placental steroidogenic pathways remain poorly characterized. This study investigated the expression of sex hormone receptors and key steroidogenic enzymes at the maternal-fetal interface in rat models of MH and MD. METHODS: At GD18, in both MH (6-propyl-2-thiouracil-induced) and MD (streptozotocin-induced) conditions, maternal hormonal dosage (free T4 or insulin, and E2, P4, and testosterone) were performed, along with placental RT-qPCR and/or immunohistochemistry analyses for steroidogenic pathway markers (ERα/Esr1, PR/Pgr, AR/Ar, Star, Cyp11a1, Hsd17b3, and Hsd3b1). RESULTS: Both MD and MH dams exhibited reduced fetal weight. These outcomes were associated with elevated plasma estradiol levels in MD rats and reduced testosterone levels in MH rats, while progesterone concentrations remained unchanged in both groups. Both MD and MH resulted in upregulated placental Esr1 expression, whereas MH additionally increased ERα protein levels in the metrial triangle. Regarding the progesterone receptor (PR), MH markedly increased its immunostaining throughout the maternal-fetal interface and both conditions elevated placental Pgr transcript levels. MH also upregulated androgen receptor (AR) protein expression in the decidua and increased placental expression of the steroidogenic enzyme Hsd3b1, while MD elevated placental Ar gene expression. CONCLUSION: These findings demonstrate that both MD and, more profoundly, MH disrupt sex steroid homeostasis and receptor expression at the rat maternal-fetal interface.

Source: Placenta

DOI: 10.1016/j.placenta.2026.01.003

Authors: Jeane Martinha dos Anjos Cordeiro, Bianca Reis Santos, Adriana Lopes da Silva, Luciano Cardoso Santos, Juneo Freitas Silva

Institution: Universidade Estadual de Santa Cruz

Language: English

Topic: Gestational Diabetes Research and Management

Subfield: Obstetrics and Gynecology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,720