Epigenetics and the Developmental Origins of Health and Disease: Parental environment signalling to the epigenome, critical time windows and sculpting the adult phenotype

Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract

“…Environmental factors can directly disturb kidney and urinary tract development, but the in utero environment may also play an indirect role in the long-term health of an individual (i.e., a phenomenon described as "fetal programming") (66). For example, the developmental origins of health and disease hypothesis has associated the parental and intrauterine environment with permanent changes in the epigenome and, as such, the clinical phenotype (67). One striking example of fetal programming is the robust association between low birth weight, a proxy for intrauterine environmental circumstances, and a reduced nephron number (68).…”

Hypotheses and models linking epigenetic transgenerational effects to population dynamics: Exploring oscillations and applications to wildlife cycles

“…T here is a growing interest in the concept of environmental exposure effects being transmitted across generations (e.g., Bonduriansky et al (2012); Skinner (2015); Walsh et al (2016); Safi-Stibler & Gabory (2020)). Effects that may be transient and wash out in a few generations or effects that may track with environmental variations are most likely to involve the epigenome because genetic mutations don't have such plasticity.…”

“…Epigenetic reprogramming has been shown to occur in the primordial germ cells of mouse embryos and while the purposes for some epigenetic changes are known, many are not (Matsui & Mochizuki (2014); Kurimoto & Saitou (2019)). In addition to germline reprogramming, the somatic epigenome of the zygote is mostly erased and is reprogrammed in the somatic cells of the embryo after implantation (Zeng & Chen (2019); Safi-Stibler & Gabory (2020)). This offers an additional mechanism for intergenerational transmission.…”

“…The possible roles of this effect in health, disease, and aging have also been explored (Sharma (2017); Nilsson et al (2018); Safi-Stibler & Gabory (2020)). These studies have focused on semi-permanent germline modifications that can be long-lived.…”

Mode of delivery and pondering potential sources of the neonatal microbiome

“…The 'Developmental Origins of Health and Disease [DOHaD] Hypothesis' [1] encompasses a substantial body of evidence which temporally and functionally link maternal exposures to adverse outcomes in her offspring (largely obesity, metabolic disorders, cardiovascular disease, and behavioral outcomes) via meaningful and persistent modulations in postnatal gene expression resulting from epigenomic changes [2]. More recently, many similar observations led to the genesis of the 'Hygiene Hypothesis', which alternately suggests that it is a lack of exposure to microbes early in life which primarily predisposes offspring to developing not only these same adverse outcomes, but atopic and allergic diseases later-in-life [3].…”