The Association Of Perfluoroalkyl Substances (PFASs) Exposure With Fallopian Tube Obstruction-and The Toxilogical Mechanisms

BACKGROUND Perfluoroalkyl substances(PFASs)are a group of synthetic chemicals and widely used in industrial and commercial applications,leading to their ubiquity in the environment and wildlife.Substantial evidence suggested that PFASs have properties of endocrine disruption and have potential adverse effects on female reproduction of immune system.OBJECTIVE The object of the present study is to explore the relationship between the exposure levels of PFASs in women with fallopian tube obstruction.In addition,animal exposure and in vitro cells studies were performed to investigate the interference effects of PFASs exposure on female reproduction,endocrine,and immune system.METHODS Population study: The present study was designed as a case-control study.Basic personal information of the participants was collected by questionnaires,the concentrations of PFASs in plasma were determined by LC-MS/MS,and statistical methods were performed to analyze the relationship between PFASs exposure levels in women with fallopian tube obstruction.Animal experiment: 8-week-old C57/BL6 female mice were exposed to PFBS and PFOS for 5 weeks.The changes of immune cells in peripheral blood and spleen,the levels of sex hormones in peripheral blood,and the expression of related proteins in ovary and uterus of mice were detected.Experiments in vitro: Mouse bone marrow derived macrophages and mouse ovarian granulosa cells were exposed to PFBS and PFOS,and the levels of related proteins and cytokines were determined.RESULT Epidemiological survey: The results showed that the higher concentrations of PFBS,PFHx S,PFOS,PFOA and PFDA in serum,the higher risk of fallopian tube obstruction.Animal experiment: PFBS and PFOS could lead to imbalance in the number and proportion of immune cells in peripheral blood and spleen of exposed mice.At the meanwhile,the levels of sex hormones in peripheral blood of mice were altered and the activation of CD200-CD200 R signaling pathway was observed in uterus and ovary of exposed mice.In vitro experiment: PFBS and PFOS exposing BMDM cells could lead to increasing the expression of CD200R1,decreasing the secretion of IL-6.PFBS and PFOS treating mouse ovarian granulosa cells could lead to increasing the expression ofestrogen receptors and CD200.CONCLUSION 1)Exposure of PFASs increases the risk of fallopian tube obstruction.2)PFBS and PFOS exposure can affect the peripheral and local reproduction-immune microenvironment,which might have potential adverse effects on female reproductive function.