Your mother's role in the aetiology of your disease; molecular mechanisms and emerging therapeutics in developmental programming.

Abstract

When my mother conceived me in the 1970s, ∼40% of pregnant women smoked (Kleinman & Kopsten, 1987) and the consumption of alcohol during pregnancy was widespread (Warren, 2015). Certainly, in the 1970s there was an emerging understanding of the link between folic acid in the diet and neural tube birth defects; however, the knowledge concerning the link between maternal health in pregnancy and her baby's development was patchy. When I was pregnant in the 2000s, there was a better understanding about the developmental consequences of my health during my pregnancies. This field is progressing; more recent research in developmental programming has identified the molecular pathways that are perturbed in response to an adverse maternal environment, and the potential therapeutics to negate these programming effects. Research has clearly demonstrated that the maternal environment before and during pregnancy, which encompasses genetics, nutrition, social determinants and metabolism, may play an important role in the mother's and her offspring's life-long health and wellbeing (Muglia et al., 2022). Stemming from the seminal work by David Barker (Barker et al., 1989), chronic non-communicable diseases appear to result from a combination of genetic, environmental and behavioural factors (McMillan et al, 2008). There is much debate about potential teratogenic effects of maternal and paternal alcohol consumption from a historical perspective (Armstrong, 1998). This has also often led to the misquotation that the ancient Greeks and Romans had an understanding about the link between alcohol during pregnancy, and the potential harm to the developing offspring (Abel, 1999). But it wasn't until the late 1960s and early 1970s, that research from Lemoine et al. (1968) and Jones and Smith (1973) described the distinct anatomical abnormalities in babies that were exposed to alcohol during pregnancy. Since that time, there has been a significant number of studies that have shown that prenatal alcohol consumption may be associated with a variety of conditions, ranging from no overt effects to poor birth outcomes such as miscarriage, fetal growth restriction and fetal alcohol spectrum disorder (Akison et al., 2019). Paternal alcohol exposure also contributes to a poor development environment (Finegersh et al., 2015). Of interest, recent research in a rodent model suggests that maternal genetics and paternal alcohol exposure may contribute to the diversity observed in fetal alcohol spectrum disorder. Specifically, that preconception paternal alcohol exposure transmits a sex-specific stressor, to developing offspring via the placenta. Further that the maternal genetic background potentially negates the effects of paternal alcohol exposure (Thomas et al., 2021). In this issue of The Journal of Physiology Steane et al. (2023) review the potential of folate and choline to reverse adverse outcomes from prenatal maternal alcohol consumption. Mechanistically, prenatal alcohol consumption is thought to alter DNA methylation and gene expression. As maternal nutritional status may determine the extent to which prenatal alcohol consumption impacts pregnancy outcomes, folate and choline supplementation has been investigated as a potential therapeutic for prenatal alcohol consumption. The review highlighted that studies have demonstrated beneficial effects of folate or choline on brain development in infants exposed to prenatal alcohol. Steane et al. suggest that future research should investigate any changes to the blastocyst and placenta in response to prenatal alcohol to better understand the mechanisms for these benefits. Further, their review suggested that optimal concentrations of folate and choline be established as part of any therapeutic regime. The review by Steane et al. (2023) summarises one presentation associated with the ‘Maternal influences on fetal development’ symposium presented at the annual Australian Physiological Society conference. This symposium also covered the programming effects of chronic kidney disease and hypertension, as well as the broad effects of maternal obesity on offspring development and health. Certainly, the first 1000 days are critical for a child's development; however, these presentations highlight the important role of the prenatal period in child health, as well as the molecular mechanisms and potential therapeutic targets that may reverse any adverse developmental programming effects. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. No competing interests declared. Sole author. None.