Maternal preconception and gestational exposure to a mixture of short half-life food chemicals altered fetoplacental development in a rabbit model, based on a French mother-child cohort

Pregnant women from the general population are exposed daily to chemicals that can affect offspring's health. The current study aimed to evaluate the effects of a mixture of chemicals on maternal and fetal health in the rabbit model, which was defined based on associations between urinary concentrations of chemicals in pregnant women from the SEPAGES cohort and offspring outcomes. From the SEPAGES cohort data, a mixture including 3 phenols, 1 paraben and four phthalates was established and used in a rabbit model. Female rabbits were exposed orally from preconception to 28 days post-conception (dpc) to this mixture (PPP exposed group, PPP) or excipient (control group, C) daily at the doses, estimated from the maximum urinary concentrations observed in the cohort. Maternal and fetoplacental phenotype were characterized. Maternal glucose concentration decreased significantly in the PPP group, before mating. At 21 dpc, ultrasound monitoring showed that fetal body length and abdominal perimeter were increased in PPP group compared to C group. At 28 dpc, heart to bodyweight ratio was increased in PPP females compared to C females. At this stage, fetal blood biochemistry showed a decrease in insulin levels, while triglycerides and total protein increased, mostly in PPP males compared to controls. Exposure to a PPP mixture defined from a human mother-child cohort impacted rabbit maternal phenotype and affected fetal health in a sex-specific manner, suggesting that this mixture could induce fetal malprogramming with long-term effects.