Tea polyphenols and EGCG induce preeclampsia-like symptoms by reducing 2-methoxyestradiol

Preeclampsia (PE), a severe pregnancy-specific disorder, poses significant health risks to both mothers and fetuses. Certain dietary habits, such as tea consumption, may affect the activity of enzymes involved in hormone metabolism, leading to alterations in the levels of important pregnancy-related hormone metabolites, such as 2-methoxyestradiol (2-MeO-E₂), which may contribute to the development of PE. To investigate the effect of tea intake on pregnancy, we conducted both in vivo and in vitro experiments. Pregnant rats were administered tea polyphenols and epigallocatechin gallate (EGCG) by gavage starting from pregnancy day 10. We found that tea polyphenols and EGCG intake during pregnancy induced PE-like symptoms in the rats such as hypertension, proteinuria and growth restriction of fetuses. These symptoms could be rescued by cotreatment of 2-MeO-E_2. Notably, the levels of the estrogen metabolite 2-MeO-E₂ in rat blood were significantly reduced, and the activity of the enzyme responsible for its metabolism, catechol-O-methyltransferase (COMT), was also inhibited. Furthermore, EGCG impaired the migration ability of HTR8/SVneo cells, which could be alleviated by 2-MeO-E₂ supplementation. These findings indicate that tea polyphenols intake during pregnancy can cause PE-like symptoms by inhibiting COMT activity and production of 2-MeO-E₂.