Exposure to endocrine disrupters impacts reproductive health
The EU-funded CONTAMED project investigated the cumulative effects of EDCs on human reproductive health. Biosamples — placenta extracts, serum and urine from three European mother–child cohorts — metabolomics profiling, in vitro bioassays and animal models were used for the studies. CONTAMED researchers made several groundbreaking discoveries and developed novel techniques for targeted chemical analyses of multiple EDCs and their exposure estimation. EDC screening and bioassay-directed fractionation techniques were combined for assessing anti-androgenic effects. The fractionated placenta extracts were separated for testing based on their bioactivity. For instance, non-polar fractions demonstrated highest androgen receptor (AR) antagonism activity. EDC estimates in placenta samples revealed a strong link between EDC exposure and congenital birth defects. For accurate assessment and profiling, researchers developed biomarkers for detecting anti-androgenic chemicals in human placenta extracts. Nine pesticides authorised for use in the EU, including dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol and pirimiphos-methyl, were discovered to have anti-androgenic properties in vitro and recommendations were made for prioritising pesticides for in vivo testing. Prostaglandins (PGs) are required for programming male sexual differentiation. Epidemiological studies revealed that consumption of paracetamol during the 12–20 week period of pregnancy increased the risk of developing testis maldescent in baby boys. An in vitro assay identified 15 pesticides that also suppress PG synthesis. Some of these pesticides — o-phenyl phenol, cypermethrin, cyprodinil, imazalil and linuron — were found to show potencies comparable to those of pain killers. For better biomonitoring data on EDCs, effects and levels of phthalate metabolites, pesticide metabolites, environmental phenols, parabens and paracetamol were assessed. Reverse dosimetry estimated human intake of EDCs from urine levels and EDC toxicokinetics. To assess joint effects of several EDCs, experimental studies involved high-end human exposure scenarios in rat and pup models. Changes in gene expression patterns from developmental exposure to EDC mixtures were characterised using transcriptomics and real-time polymerase chain reaction (RT-PCR). This bias-free gene selection approach revealed the genes affected or targeted by EDCs. CONTAMED research conclusively indicated that current regulatory measures are inadequate to combat combined EDC exposure. Research outcomes will inform policymakers on categorising and regulating EDCs to minimise exposure.
