Organ-specific lithium accumulation and its toxic effects on female reproduction.

Li exposure is becoming a new prominent major issue in energy-environment-health field. However, its reproductive health risk has been less explored. In this study, we find that exposure to 28-fold REED (really environmental exposure dose) of Li is enough to induce mouse miscarriage by altering the structures and functions of placenta. Exposure to ≥ 5.6-fold REED of Li is enough to alter the structure and functions of ovary and placenta, and exposure to ≥ 28-fold REED of Li alters fetus morphology and uterus functions, showing a susceptibility to Li exposure as the order ovary > placenta > fetus > uterus. Some characteristics (such as AMH (anti-müllerian hormone) levels in serum, the mRNA levels of Pgr (progesterone receptor) and Nr2f2 in placenta, and the mRNA levels of Cyp19A1 and Sohlh2 in Ovary) are significantly altered with exposure to 5.6-fold REED of Li, which could be used as sensitive targets to predict reproductive health risk with Li exposure. Moreover, the doses of Li in clinical Li treatment (28- or 56-fold REED of Li) should be more cautious, especially for women. Collectively, this study identifies Li exposure as a new risk factor for female reproductive healthy in energy-environment-health field, which deserves the critical attention by governments, enterprises, and hospitals.