Mycoestrogen Exposure during Pregnancy: Impact of the ABCG2 Q141K Variant on Birth and Placental Outcomes.

Background: Zearalenone (ZEN) is an estrogenic mycotoxin ("mycoestrogen") that contaminates global grain crops leading to detectable concentrations of ZEN and its metabolites, including the synthetic version $\alpha$-zearalanol (also called zeranol; ZER), in human populations. Despite in vitro and in vivo animal evidence of endocrine disruption by ZEN, there has been limited investigation in humans.

Objectives: To examine markers of fetal growth following prenatal exposure to ZEN and evaluate the role of the placental efflux transporter BCRP/ABCG2 in protecting against ZEN's potential fetoplacental toxicity.

Methods: Placentas were collected from participants ($n=271$) in the Understanding Pregnancy Signals and Development cohort (Rochester, New York, USA). Placental ZEN and its metabolites were analyzed from tissue samples using HPLC-MS. Birth weights and placental weights were obtained from medical records and direct measurement, respectively; fetoplacental weight ratio (FPR) was calculated by dividing birth weight by placental weight. Covariate-adjusted generalized linear regression models were used to examine ZEN, ZER, and total mycoestrogens (sum of ZEN, ZER, and their metabolites) in relation to birth length, birth weight, placental weight and FPR. We additionally stratified models by infant sex and ABCG2 C421A (Q141K) genotype.

Results: Mycoestrogens were detected in 84% of placentas (median ZEN: $0.010\text{\hspace{0.17em}ng}/g$) and total mycoestrogens were associated with lower FPR [$-0.20$; 95% confidence interval (CI): $-0.32$, $-0.08$], particularly in female infants ($-0.31$; 95% CI: $-0.52$, $-0.09$). Associations with birth weight were inverse and overall nonsignificant. Among the 17% of participants with the reduced function 421A ABCG2 variant (AA or AC), total mycoestrogens were associated with lower birth weight ($-113.5g$; 95% CI: $-226.5$, $-0.50$), whereas in wild-type individuals, total mycoestrogens were associated with higher placental weight (9.9; 95% CI: 0.57, 19.2) and reduced FPR ($-0.19$; 95% CI: $-0.33$, $-0.05$).

Discussion: Results from this epidemiological study of prenatal mycoestrogen exposure and perinatal health suggest that mycoestrogens may reduce placental efficiency, resulting in lower birth weight, particularly in female and ABCG2 421A infants. https://doi.org/10.1289/EHP14478.