Molecular mechanisms of induction of persistent changes by estrogenic chemicals on female reproductive tracts and external genitalia

The effects of environmental endocrine-disrupting chemicals (EDCs) are a great and growing concern for human and animal development and life. The reproductive organs are considered as a primary target of EDCs, yet the effects on reproductive organs can extend to other body systems. Perinatal diethylstilbestrol (DES)-exposed mice exhibit various reproductive organ abnormalities. The perinatal DES-exposure model has allowed insight into our understanding of the mechanisms of persistent reproductive organ abnormalities elicited by exposure to estrogens and/or estrogenic EDCs. The persistent changes in the vagina of neonatally DES-exposed mice result from sustained expression of growth factors by ligand-independent transcriptional activation of the estrogen receptor. Developmental regulatory genes, such as Wnt and Hox genes, are also targets of DES during fetal stages and altered gene expression can induce malformations of the reproductive organs. In this review, we focus on the development of female reproductive tracts and external genitalia, and discuss the recent progress in understanding the disruptive effects of estrogens and EDCs on these organs.