Endocrine disrupting chemicals cross the placenta barrier and affect fetal weight and sex ratio in mice

MEYER N; SANTAMARIA CG; SCHUMACHER A; MÜLLER JE; RODRIGUEZ HA; LUQUE EH; ZENCLUSSEN ML; TEGLIA CM; CULZONI MJ; ZENCLUSSEN AC

Leipzig

Congreso; XXII Lipid Meeting; 2021

Objective: Endocrine disrupting chemicals (EDCs), like Bisphenol A (BPA), 17--ethinylestradiol (EE2), and Benzophenone 3 (BP-3), accumulate in our environment and interfere with the natural action of hormones, causing adverse effects on wildlife and human beings. Besides disturbance of growth and development and negative influence on reproduction, exposure to EDCs can lead to increased susceptibility to diseases like cancer, diabetes, and obesity. However, mechanisms and their influence during sensitive life phases, like pregnancy, are not yet clearly understood.Methods: 8-10 weeks old female C57BL6/J mice were paired with BALB/c males and treated with BPA (50 μg/kg bodyweight (bw)/day), EE2 (0.005 or 5 μg/kg bw/day) from gestation day (gd) 0 to gd7 by oral gavage or with BP-3 (50 mg/kg bw/day) from gd1 to gd7 by dermal application. Sham-treated mice served as controls. Fetal/placental growth and maternal/fetal blood flow parameters were assessed by high frequency ultrasound. Implantation/abortion rates as well as spiral artery (SA) parameters were recorded. Offspring and placental weights were determined. A further BP-3 group was allowed to give birth, and mated afterwards. Second pregnancy and pup weights were analyzed in this group. Also, BP-3 was analyzed in serum and amniotic fluid by chromatography.ResultsBPA exposure affected SA remodeling and impaired fetal and placental growth. 40.5 % of the progeny of BPA-treated mothers was growth restricted. Fetuses of high dose EE2 exposed mothers die intrauterine at gd10. In contrast, low dose EE2 exposed mothers have impaired remodeled SA, show a higher placental weight and 38.5 % of pups were large for gestational age. BP-3 exposure affected fetal weights and maternal blood flow in the first pregnancy, with 16.13 % of the first progeny being growth restricted at gd14. In the second pregnancy, placental weights were decreased. In both pregnancies, BP-3 could be detected in serum and amniotic fluid. Offspring of the second progeny showed lower weights, with males being more affected than females. Importantly, there was a shift in sex ratio of offspring towards females.Conclusions: EDCs may affect pregnancy by multiple mechanisms. Our data support the concept of EDCs crossing the placental barrier and directly affect the fetuses. Short-term exposure to selected EDCs during early pregnancy negatively impacted placental and fetal weights that in turn may promote the development of disease later in life.