Mercury chloride exposure disrupts placental function and embryonic methionine metabolism leading to neural tube defects in ICR mice.

The aim of the study was to explore the precise mechanisms involved in maternal mercury exposure induced neural tube defects (NTDs). We established a mouse model of mercury chloride (HgCl2)-induced embryo NTDs using ICR mice, and investigated the roles of amino acid transport and associated methionine metabolic disorders in the placenta and fetus. Oral administration of 0, 1.5, 3, and 4.5 mg/kg/d HgCl2 to pregnant ICR mice was performed between gestation days 5.5 and 9.5, with assessments conducted on gestation day 10.5. The incidence of NTDs was significantly elevated in the 3 mg/kg/d group without causing more maternal mortality or more embryo loss, comparing with the control group. So, 3 mg/kg/d was chosen as appropriate exposure dose for mechanism experiment. During exposure, the placenta intercepted most of the mercury and reduced its transfer to the embryo. This change is associated with alterations in placental transporters. Compared to the control group, the mercury-exposed group exhibited higher levels of oxidative stress and showed greater apoptosis in Placenta. Placental apoptosis was negatively correlated with embryonic mercury content. Embryos from the exposure group exhibited significantly elevated levels of methionine (Met) and cystine (Cys) but markedly decreased levels of S-adenosylmethionine (SAM) and homocysteine (Hcy). Overall，Maternal exposure to HgCl2 induces NTDs in offspring. Such exposure may be associated with heightened apoptosis of placental cells and oxidative stress, apoptosis of fetal neural tube cells, and suppression of the transformation of Met to SAM in embryos.