Endocrine disrupting chemicals impact on ovarian aging: Evidence from epidemiological and experimental evidence.

Endocrine-disrupting chemicals (EDCs) are ubiquitous in daily life, but their harmful effects on the human body have not been fully explored. Recent studies have shown that EDCs exposure could lead to infertility, menstrual disorder and menopause, resulting in subsequent effects on female health. Therefore, it is of great significance to clarify and summarize the impacts of EDCs on ovarian aging for explaining the etiology of ovarian aging and maintaining female reproductive health. Here in this review, we focused on the impacts of ten typical environmental contaminants on the progression of ovarian aging during adult exposure, including epidemiological data in humans and experimental models in rodents, with their clinical phenotypes and underlying mechanisms. We found that both persistent (polychlorinated biphenyls, perfluoroalkyl and polyfluoroalkyl substances) and non-persistent (phthalates) EDCs exposure could increase an overall risk of ovarian aging, leading to the diminish of ovarian reserve, decline of fertility or fecundity, irregularity of the menstrual cycle and an earlier age at menopause, and/or premature ovarian insufficiency/failure in epidemiological studies. Among these, the loss of follicles can also be validated in experimental studies of some EDCs, such as BPA, phthalates, parabens and PCBs. The underlying mechanisms may involve the impaired ovarian follicular development by altering receptor-mediated pro-apoptotic pathways, inducing signal transduction and cell cycle arrest and epigenetic modification. However, there were inconsistent results in the impacts on fertility/fecundity, menstrual/estrous cycle and hormone changes response to different EDCs, and differences between human and animal studies. Our review summarizes the current state of knowledge on ovarian disrupters, highlights their risks to ovarian aging and identifies knowledge gaps in humans and animals. We therefore propose that females adopt healthy lifestyle changes to minimize their exposure to both persistent and non-persistent chemicals, that have the potential damage to their reproductive function.

Ding T ，Yan W ，Zhou T ，Shen W ，Wang T ，Li M ，Zhou S ，Wu M ，Dai J ，Huang K ，Zhang J ，Chang J ，Wang S ... -  《-》

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. Experimental models and epidemiologic studies suggest that PFAS exposures target the ovary and represent major risks for women's health. This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function. A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords (e.g. ovarian, reproductive, follicle, oocyte) to specific keywords (including menarche, menstrual cycle, menopause, primary ovarian insufficiency/premature ovarian failure, steroid hormones), based on the authors' knowledge of the topic and key terms. Clinical evidence demonstrates the presence of PFAS in follicular fluid and their ability to pass through the blood-follicle barrier. Although some studies found no evidence associating PFAS exposure with disruption in ovarian function, numerous epidemiologic studies, mostly with cross-sectional study designs, have identified associations of higher PFAS exposure with later menarche, irregular menstrual cycles, longer cycle length, earlier age of menopause and reduced levels of oestrogens and androgens. Adverse effects of PFAS on ovarian folliculogenesis and steroidogenesis have been confirmed in experimental models. Based on laboratory research findings, PFAS could diminish ovarian reserve and reduce endogenous hormone synthesis through activating peroxisome proliferator-activated receptors, disrupting gap junction intercellular communication between oocyte and granulosa cells, inducing thyroid hormone deficiency, antagonising ovarian enzyme activities involved in ovarian steroidogenesis or inhibiting kisspeptin signalling in the hypothalamus. The published literature supports associations between PFAS exposure and adverse reproductive outcomes; however, the evidence remains insufficient to infer a causal relationship between PFAS exposure and ovarian disorders. Thus, more research is warranted. PFAS are of significant concern because these chemicals are ubiquitous and persistent in the environment and in humans. Moreover, susceptible groups, such as foetuses and pregnant women, may be exposed to harmful combinations of chemicals that include PFAS. However, the role environmental exposures play in reproductive disorders has received little attention by the medical community. To better understand the potential risk of PFAS on human ovarian function, additional experimental studies using PFAS doses equivalent to the exposure levels found in the general human population and mixtures of compounds are required. Prospective investigations in human populations are also warranted to ensure the temporality of PFAS exposure and health endpoints and to minimise the possibility of reverse causality.

Ding N ，Harlow SD ，Randolph JF Jr ，Loch-Caruso R ，Park SK ... -  《-》

Exposure to modern, widespread environmental endocrine disrupting chemicals and their effect on the reproductive potential of women: an overview of current epidemiological evidence.

Karwacka A ，Zamkowska D ，Radwan M ，Jurewicz J ... -  《-》

The Influence of Environmental Factors on Ovarian Function, Follicular Genesis, and Oocyte Quality.

Huang J ，Zeng H 《Advances in Experimental Medicine and Biology》

The adverse role of endocrine disrupting chemicals in the reproductive system.

Reproductive system diseases pose prominent threats to human physical and mental well-being. Besides being influenced by genetic material regulation and changes in lifestyle, the occurrence of these diseases is closely connected to exposure to harmful substances in the environment. Endocrine disrupting chemicals (EDCs), characterized by hormone-like effects, have a wide range of influences on the reproductive system. EDCs are ubiquitous in the natural environment and are present in a wide range of industrial and everyday products. Currently, thousands of chemicals have been reported to exhibit endocrine effects, and this number is likely to increase as the testing for potential EDCs has not been consistently required, and obtaining data has been limited, partly due to the long latency of many diseases. The ability to avoid exposure to EDCs, especially those of artificially synthesized origin, is increasingly challenging. While EDCs can be divided into persistent and non-persistent depending on their degree of degradation, due to the recent uptick in research studies in this area, we have chosen to focus on the research pertaining to the detrimental effects on reproductive health of exposure to several EDCs that are widely encountered in daily life over the past six years, specifically bisphenol A (BPA), phthalates (PAEs), polychlorinated biphenyls (PCBs), parabens, pesticides, heavy metals, and so on. By focusing on the impact of EDCs on the hypothalamic-pituitary-gonadal (HPG) axis, which leads to the occurrence and development of reproductive system diseases, this review aims to provide new insights into the molecular mechanisms of EDCs' damage to human health and to encourage further in-depth research to clarify the potentially harmful effects of EDC exposure through various other mechanisms. Ultimately, it offers a scientific basis to enhance EDCs risk management, an endeavor of significant scientific and societal importance for safeguarding reproductive health.

Pan J ，Liu P ，Yu X ，Zhang Z ，Liu J ... -  《Frontiers in Endocrinology》