The ACCEPT birth cohort: Real-life serum mixtures of Persistent Organic Pollutants in pregnant women disrupt estrogen and androgen receptor transactivity and affect fetal growth

Humans are exposed to complex mixtures of chemicals with different biological effects. The lipophilic persistent organic pollutants (lipPOPs) including polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) have long half-lives and bioaccumulate in humans and possess endocrine-disrupting potentials. Studying the combined effects of actual lipPOP mixtures is particularly important in highly exposed populations such as Arctic Indigenous peoples.The aim of the present study was to measure transactivity of lipPOPs serum extracts from 482 Greenlandic pregnant women on estrogen receptor (ER) and androgen receptor (AR) function and evaluate possible associations to neonate birth outcomes.LipPOPs mixture was extracted using SPE-HPLC, and ER and AR transactivity was measured using reporter gene bioassays.Around 29.7% of the lipPOP extracts exhibited agonistic xenoestrogenic effects and 10.8% antagonized the 17-β-estradiol (E2)-induced ER transactivaty. For the AR transactivaty, 54.9% of lipPOP extracts elicited AR agonistic effect, and 39.9% antagonized the dihydrotestosterone (DHT)-induced AR transactivity.The xenoandrogenic transactivity (XAR) was inversely associated with the serum levels of estrogenic PCBs and the principal component containing PCBs and OCPs. A significant inverse association was found between XAR and birth weight, and the association was pronounced in female neonates. Smoking can modify the inverse associations between xenoestrogenic transactivity (XER) and birth weight, birth length and head circumference.In conclusion, the actual serum mixture of lipPOPs in pregnant women elicited endocrine disrupting potential via disruption of the ER and AR function and have sex-specific potential to affect fetal growth especially for girls.