At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte cytosine methylation and chromatin patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic effects interact with conditions at conception to program the developmental trajectory of the embryo and fetus, ultimately affecting the lifetime health of the child. These insights compel us to revise generally held notions to accommodate the prospect that biological parenting commences well before birth, even prior to conception.

https://science.sciencemag.org/content/sci/345/6198/756.full.pdf

Parenting from before conception

Bisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferas...

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Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio)

Bisphenol A and its analogues: A comprehensive review to identify and prioritize effect biomarkers for human biomonitoring

The growing field of 'Developmental Origin of Health and Disease' (DOHaD) generally reflects environmental influences from mother to child. The importance of maternal lifestyle, diet and other environmental exposures before and during gestation period is well recognized. However, few epidemiological designs explore potential influences from the paternal environment on offspring health. This is surprising given that numerous animal models have provided evidence that the paternal environment plays a role in a non-genetic inheritance of pre-conceptional exposures through the male germ line. Recent findings in humans suggest that the epigenome of sperm cells can indeed be affected by paternal exposures. Defects in epigenetic sperm mechanisms may result in persistent modifications, affecting male fertility or offspring health status. We addressed this issue at the LATSIS Symposium 'Transgenerational Epigenetic Inheritance: Impact for Biology and Society', in Zurich, 28-30 August 2017, and here provide important arguments why environmental and lifestyle-related exposures in young men should be studied. The Paternal Origins of Health and Disease (POHaD) paradigm was introduced to stress the need for more research on the role of the father in the transmission of acquired environmental messages from his environment to his offspring. A better understanding of pre-conceptional origins of disease through the paternal exposome will be informative to the field of transgenerational epigenetics and will ultimately help instruct and guide public health policies in the future.

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POHaD: why we should study future fathers.

Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure.

Bisphenol A (BPA) is an endocrine disruptor with potentially harmful effects on humans. However, epigenetic mechanisms that modulate the effects of BPA remain unclear. Methylation of long interspersed nucleotide elements (LINE-1) is a marker of genome-wide methylation status. This study aims to examine whether BPA exposure was associated with LINE-1 methylation changes in men. Male factory workers in Hunan, China (N = 149) were studied, 77 with BPA exposure in workplace (BPA-exposed group) and 72 without BPA exposure in workplace (control group). Pre-shift and post-shift urine samples were collected from the BPA-exposed group and spot urine samples were collected from the control group. Urine samples were assessed for BPA. In addition, blood and semen samples were collected from both groups for LINE-1 methylation analysis. In multivariate analysis adjusted for age, education, smoking habits and alcohol consumption, sperm LINE-1 methylation level was significantly lower in BPA exposed workers (p < 0.001) compared to that in the unexposed workers. Linear regression analysis also showed that log-transformed urine BPA levels were inversely associated with sperm LINE-1 methylation (p < 0.0001), but not peripheral blood cell LINE-1 methylation. Moreover, the association between urine BPA level and semen quality was not attenuated after adjustments for LINE-1 level. In summary, the observed independent relationship between BPA exposure and LINE-1 methylation may have public health implications on reproductive health in men because of ubiquitous exposure to BPA.

Y. Li

Papers

LINE-1 hypomethylation in spermatozoa is associated with Bisphenol A exposure