Di(2‐ethylhexyl)phthalate: Adverse effects on folliculogenesis that cannot be neglected

Primordial follicle formation and the subsequent transition of follicles through primary and secondary stages constitute crucial events of oogenesis. In particular, in mammals, defects in the processes that precede and accompany the formation of the primordial follicle pool can affect the size of this population significantly, while alterations in follicle activation, growth and maturation can result in premature depletion of the follicle reserve or cause follicle arrest at immature stages. Over the last decade, in vitro and in vivo approaches have been used to provide evidence that exposure to di(2‐ethylhexyl)phthalate(DEHP), the most widely used plasticizer, has a deleterious effect on various stages of folliculogenesis in rodents. There is growing concern, supported by epidemiological and experimental data, that DEHP may have similar effects in women. This article reviews the evidence, with particular reference to our own findings, that DEHP may actually exert a variety of adverse effects on mammalian folliculogenesis from early to final stages of oogenesis, including altered development of the primordial germ cells, impaired fetal oocyte survival and meiotic progression, reduced oocyte nest breakdown, acceleration of primordial follicle activation, altered follicle steroidogenesis and increased follicle atresia. These effects can cause serious complications for reproductive and nonreproductive women's health. In addition, emerging data indicate that phthalates, including DEHP, may cause subtle epigenetic changes in germ cells that can be transmitted to subsequent generations, with potential negative effects on human health. Environ. Mol. Mutagen. 57:589–604, 2016. © 2016 Wiley Periodicals, Inc.