Cumulative Exposure to Phthalates and Their Alternatives and Associated Female Reproductive Health: Body Burdens, Adverse Outcomes, and Underlying Mechanisms

The global birth rate has recently shown a decreasingtrend, andexposure to environmental pollutants has been identified as a potentialfactor affecting female reproductive health. Phthalates have beenwidely used as plasticizers in plastic containers, children'stoys, and medical devices, and their ubiquitous presence and endocrine-disruptingpotential have already raised particular concerns. Phthalate exposurehas been linked to various adverse health outcomes, including reproductivediseases. Given that many phthalates are gradually being banned, agrowing number of phthalate alternatives are becoming popular, suchas di-(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), di-(2-ethylhexyl)adipate (DEHA), and di-(2-ethylhexyl) terephthalate (DEHTP), and theyare beginning to have a wide range of environmental effects. Studieshave shown that many phthalate alternatives may disrupt female reproductivefunction by altering the estrous cycle, causing ovarian follicularatresia, and prolonging the gestational cycle, which raises growingconcerns about their potential health risks. Herein, we summarizethe effects of phthalates and their common alternatives in differentfemale models, the exposure levels that influence the reproductivesystem, and the effects on female reproductive impairment, adversepregnancy outcomes, and offspring development. Additionally, we scrutinizethe effects of phthalates and their alternatives on hormone signaling,oxidative stress, and intracellular signaling to explore the underlyingmechanisms of action on female reproductive health, because thesechemicals may affect reproductive tissues directly or indirectly throughendocrine disruption. Given the declining global trends of femalereproductive capacity and the potential ability of phthalates andtheir alternatives to negatively impact female reproductive health,a more comprehensive study is needed to understand their effects onthe human body and their underlying mechanisms. These findings mayhave an important role in improving female reproductive health andin turn decreasing the number of complications during pregnancy.

Automated summary

The decline in global birth rates is attributed to the potential effects of environmental pollutants on female reproductive health. Phthalates, widely used in plastic containers, toys, and medical devices, have raised concerns due to their endocrine-disrupting potential. As phthalates are being banned, alternative substances such as DINCH, DEHA, and DEHTP are gaining popularity and have shown various effects on female reproductive function. Studies have shown that these alternatives may disrupt the estrous cycle, cause follicular atresia, and prolong the gestational cycle, highlighting the need for a comprehensive understanding of their effects and underlying mechanisms on female reproductive health.