Gene-Dioxin Interactions and Time to Pregnancy in the Seveso Women’s Health Study

Abstract

TPS 634: Health effects of pops, voc and other chemicals, Johan Friso Foyer, Floor 1, August 27, 2019, 3:00 PM - 4:30 PM Background/Aim: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, has been associated with reduced fertility in multiple animal species. TCDD is proposed to impact fertility via altered activity of the aryl hydrocarbon receptor (AhR) pathway, which regulates diverse biological and developmental processes, including xenobiotic metabolism. The Seveso Women’s Health Study (SWHS) followed up 981 women exposed to TCDD in a chemical factory explosion in 1976. Twenty years later, we reported longer time to pregnancy (TTP) associated with individual 1976 serum TCDD levels, but the youngest women had not yet attempted pregnancy. Now, 40 years after the explosion, when most women will have completed their families, we aim to re-examine the relationship of TCDD exposure with TTP and assess whether variations in AhR pathway genes modify this relationship. Methods: Of 617 women who had attempted pregnancy after the explosion, 367 delivered a live birth not associated with contraceptive failure. We examined the relationship of 1976 serum TCDD levels to TTP (parameterized as the monthly probability of conception within the first 12 months of trying) using discrete-time Cox proportional hazards regression. We also utilized genotype data (87 SNPs across 7 AhR pathway genes) to examine gene-environment interactions between AhR pathway variants and TCDD levels on TTP. Results: Women averaged 26.7 (±4.3) years at the time of attempting pregnancy. Median TTP was 2 months, with 17.2% taking 12 or more months to conceive. Consistent with our previous findings, a 10-fold increase in serum TCDD was associated with longer TTP (adjusted fecundability odds ratio = 0.80; 95%CI: 0.66, 0.98). In preliminary analyses, we found one SNP in AHRR which adversely modified the association between TCDD levels and TTP, implicating gene-environment interaction. Conclusions: These results suggest that TCDD exposure is associated with reduced fertility in the Seveso cohort; gene-environment interaction may play a role.