VEGFR2在孕期镉暴露胎盘血管新生及胎儿发育中的作用及机制

Cadmium (Cd) is a toxic heavy metal that is ubiquitous in the environment. Cadmium exposure during pregnancy mainly acts a toxic to accumulation in placenta. Our previous cohort study showed that a significant association between Cd concentrations in maternal urine and adverse pregnancy outcomes including preterm birth, low birth weight, etc.; however, the mechanism for Cd to affect adverse pregnancy outcomes remain unknown. Our preliminary animal experiments show that cadmium exposure during pregnancy resulted in a significant decrease in the placental weight, angiogenesis, VEGFR2 expression, embryo weight and increase in the incidence of preterm birth. Our results suggest that VEGFR2 may play an important role in Cd-induced inhibition of placental angiogenesis and adverse pregnancy outcomes. The present study will investigate the role of VEGFR2 in the regulation of placental angiogenesis and adverse pregnancy outcomes as well as the underlying molecular mechanism by administration of recombinantVEGFR2 protein, VEGFR2 knockout mice and cultured endothelial cells. Finally, we will elucidate the mechanism of Cd to induce abnormal placental development and adverse pregnancy outcomes, and provide a new prevention and therapeutic strategies for adverse pregnancy outcomes.

镉是环境中普遍存在的有毒重金属。孕期镉暴露主要在胎盘中蓄积对胚胎产生毒性作用。我们既往人群研究表明孕妇尿镉浓度与不良妊娠结局（早产、低出生体重等）密切正相关，但是镉引起不良妊娠结局的机制不清楚。我们前期动物实验表明大鼠孕期镉暴露可引起胎盘重量明显减轻、血管新生减少、VEGFR2表达降低、早产及胚胎变小，提示VEGFR2可能参与镉损伤胎盘血管新生的作用。本研究应用VEGFR2重组蛋白注射和VEGFR2敲除小鼠及体外内皮细胞培养模型，研究镉抑制胎盘血管新生及VEGFR2 表达的分子机制；明确VEGR2在镉影响血管新生、导致胎盘发育及不良妊娠结局中的作用；探讨VEGR2促进血管新生及保护胎盘发育的分子机制。最后阐明VEGR2保护镉毒性导致胎盘发育及不良妊娠结局的分子机制，为预防孕期镉暴露不良妊娠结局提供新的策略。