Multigenerational And Transgenerational Effects Of Endocrine Disrupting Chemicals

Background: Maternal exposure to endocrine disrupting chemicals(EDCs)is associated with long-term hormone-dependent effects that are sometimes not revealed until maturity,middle age or adulthood.Aim: The aim of this study was to assess state of knowledge on the multigenerational and transgenerational effects associated with in utero and lactational exposure to selected EDCs in animal experiments and human epidemiological studies.Methodology: A systematic search of literature was performed in Pub Med,Web of Science and Toxline databases for relevant human and experimental animal studies on October 29,2018.An additional search was performed for studies published by through September 2019 for epidemiological studies that examined in utero exposure to persistent and non-persistent EDCs,and considered anogenital distance in offspring as an outcome.Search results were screened for relevance,and studies that met the inclusion criteria were evaluated and qualitative data extracted for analysis.Results: In the first study,the search yielded 73 relevant human and 113 animal studies.Results from studies show that in utero and lactational exposure to EDCs is associated with impairment of reproductive,immunologic,metabolic,neurobehavioral and growth physiology of the exposed offspring up to the fourth generation without additional exposure.Little convergence is seen between animal experiments and human studies in terms of the reported adverse health effects which might be associated with methodologic challenges across the studies.The second study contained 16 investigations examining exposure to persistent EDCs(9 studies)and non-persistent EDCs(7 studies).Some individual studies reported an inverse association between exposure to BPA,dioxins,perfluoroalkyl substances and organochlorides,and AGD in both male and female offspring.Meta-analysis of 3 studies found a small reduction of AGD in female offspring exposed to BPA.Conclusion: Based on the available animal and human evidence,in utero and lactational exposure to EDCs is detrimental to the offspring.However,more human studies are necessary to clarify the toxicological and patho-physiological mechanisms underlying these effects.