Multigenerational Musculoskeletal Anomalies After In Utero Exposure to Synthetic Xenohormones (Diethylstilbestrol, Ethinyl Estradiol and/or Progestins)

In a previous review, after recalling the somatic and psychiatric effects of synthetic estrogens in children exposed in utero and their offspring, despite warnings from the moment they were put on the market, we reported that synthetic progestins have similar effects. In the present work, based on data from a retrospective French cohort of patients whose mothers (first generation) were treated with diethylstilbestrol (DES), ethinyl estradiol and/or synthetic progestins during pregnancy, we highlight the presence of congenital malformations, particularly of the musculoskeletal system, in second (directly exposed in utero) and third-generation girls and boys. The analyzed data were from 17 families and included 30 second generation children (20 girls and 10 boys who were prenatally exposed) and 31 third generation grandchildren (7 girls and 24 boys) whose mothers (second generation) some of them received additional hormonal treatment (progestins) to promote fertility or for in vitro fertilization procedures. This is the first time that congenital musculoskeletal malformations have been described in the grandchildren of women treated with xenohormones. The epigenetic and hormonal mechanisms involved in the teratogenic effects of these endocrine disruptors are discussed.