Relationship between ovarian reserve and parental exposure in first-generation offspring of Yusho patients

In mice and rats, exposure to dioxins has been shown to have adverse effects on ovarian function in first-generation offspring (F1). However, in humans, this effect has not been clearly established. Exposure to food oil contaminated with dioxins, especially 2,3,4,7,8-pentachlorinated dibenzofuran (PeCDF) caused the onset of complex toxicity-related symptoms known as Yusho disease. The aim of this study was to investigate the intergenerational effects of PeCDF exposure on ovarian function in F1 offspring. To this end, we investigated the relationship between the standard deviation (z-score) of anti-Müllerian hormone (AMH) concentration and Yusho exposure status. Of 55 F1 offspring born to Yusho patients, 41 were enrolled in this study after applying the exclusion criteria. The median age (range) was 43 (22-50) years. Yusho exposure originated from the mother in 31 (75.6%) cases, the father in 1 (2.4%) case, and both parents in 9 (22.0%) cases. The median blood AMH concentration and z-score of the Yusho group were low, at 0.27 ng/mL and -1.61, respectively; the z-scores were lower than 0, corresponding to the mean of the age-matched healthy women used to derive the reference distribution (one-sample Wilcoxon signed-rank test, W =  - 633, p < 0.001). In a sensitivity analysis restricted to F1 offspring with maternal exposure only (n = 31), the median z-score was -1.69 (one-sample Wilcoxon signed-rank test, W = 56, p = 0.0002), confirming the robustness of this finding. This evidence suggests that Yusho exposure adversely affects the ovarian reserve in F1 offspring.