Agarwal A, et al. World J Mens Health. 2019 Sep;37(3):296-312. https://doi.org/10.5534/wjmh.190055

Environmental exposures, psychosocial stressors and nutrition are all potentially important influences that may impact health outcomes directly or via interactions with the genome or epigenome over generations. While there have been clear successes in large-scale human genetic studies in recent decades, there is still a substantial amount of missing heritability to be elucidated for complex childhood disorders. Mounting evidence, primarily in animals, suggests environmental exposures may generate or perpetuate altered health outcomes across one or more generations. One putative mechanism for these environmental health effects is via altered epigenetic regulation. This review highlights the current epidemiologic literature and supporting animal studies that describe intergenerational and transgenerational health effects of environmental exposures. Both maternal and paternal exposures and transmission patterns are considered, with attention paid to the attendant ethical, legal and social implications.

Exposure to non-persistent chemicals in consumer products is ubiquitous and associated with endocrine-disrupting effects. These effects have been linked to infertility and adverse pregnancy outcomes in some studies and could affect couple fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). Few epidemiologic studies have examined the impact of non-persistent chemicals specifically on TTP, and the results of these studies have not been synthesized. We undertook a systematic review to summarize the strength of evidence for associations of common non-persistent chemicals with couple fecundability and to identify gaps and limitations in the literature, with the aim of informing policy decisions and future research. We performed an electronic search of English language literature published between 1 January 2007 and 25 August 2017 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE, POPLINE and DESTAF. We included human retrospective and prospective cohort, cross-sectional and case-control studies that examined phthalates, bisphenol A, triclosan, triclocarban, benzophenones, parabens and glycol ethers in consumer products, and considered TTP or fecundability as an outcome among women, men and couples conceiving without medical assistance. We excluded editorials, opinion pieces, introductions to special sections, articles that described only lifestyle (e.g. caffeine, stress) or clinical factors (e.g. semen parameters, IVF success). Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. The search returned 3456 articles. There were 15 papers from 12 studies which met inclusion criteria, of which eight included biomarkers of chemical exposure. Studies varied widely in terms of exposure characterization, precluding a meta-analytic approach. Among the studies that measured exposure using biospecimens, results were equivocal for associations between either male or female phthalate exposure and TTP. There was preliminary support for associations of female exposure to some parabens and glycol ethers and of male exposure to benzophenone with longer TTP, but further research and replication of these results are needed. The results provided little to no indication that bisphenol A, triclocarban or triclosan exposure was associated with TTP. Despite a growing literature on couple exposure to non-persistent endocrine-disrupting chemicals and fecundability, evidence for associations between biologically measured exposures and TTP is limited. Equivocal results with different non-persistent chemical compounds and metabolites complicate the interpretation of our findings with respect to TTP, but do not preclude action, given the documented endocrine disrupting effects on other reproductive outcomes as well as fetal development. We therefore advocate for common-sense lifestyle changes in which both females and males seeking to conceive minimize their exposure to non-persistent chemicals. CRD42018084304.