Incorporating epigenetic mechanisms to advance fetal programming theories

Abstract

Decades of fetal programming research indicates that we may be able to map the origins of many physical, psychological, and medical variations and morbidities before the birth of the child. While great strides have been made in identifying associations between prenatal insults, such as undernutrition or psychosocial stress, and negative developmental outcomes, far less is known about how adaptive responses to adversity regulate the developing phenotype to match stressful conditions. As the application of epigenetic methods to human behavior has exploded in the last decade, research has begun to shed light on the role of epigenetic mechanisms in explaining how prenatal conditions shape later susceptibilities to mental and physical health problems. In this review we describe and attempt to integrate two dominant fetal programming models: the cumulative stress model (a disease-focused approach) and the match-mismatch model (an evolutionary-developmental approach). In conjunction with biological sensitivity to context theory, we employ these two models to generate new hypotheses regarding epigenetic mechanisms through which prenatal and postnatal experiences program child stress reactivity and, in turn, promote development of adaptive versus maladaptive phenotypic outcomes. We conclude by outlining priority questions and future directions for the fetal programming field.

Maternal caregiving and DNA methylation in human infants and children: Systematic review

“…Among the reviewed studies, those that included an initial adverse experience were in line with this hypothesis. In the presence of initial stressful circumstances, a sensitive maternal behavior proved to have a critical effect at an epigenetic level on the genes that are normally negatively affected by adverse experience ( SCL6A4 and NR3C1 ) . These findings support recently proposed interpretation (ie, match‐mismatching model) of epigenetic studies on fetal programming, extending this theoretical view to a wider life‐span framework.…”

“…In the presence of initial stressful circumstances, a sensitive maternal behavior proved to have a critical effect at an epigenetic level on the genes that are normally negatively affected by adverse experience (SCL6A4 and NR3C1). 10,36,37,40 These findings support recently proposed interpretation (ie, match-mismatching model) of epigenetic studies on fetal programming, 38 extending this theoretical view to a wider life-span framework. Moreover, a gender effect also emerged, with females being more susceptible to maternal caregiving effects compared to males.…”

“…As such, more difficult interpretation of behavioral epigenetics findings lies in the complexity of human interactions which makes it hard to isolate specific maternal behavior and to consider them as more prominent or generally valid. In the reviewed studies, different conceptualizations (and the related measures) of maternal caregiving behavior emerged as significantly associated with the DNA methylation status investigated and/or as a significant buffering proxy to protect infants from detrimental consequences of adversity exposures earlier in life . Among different maternal caregiving displays, maternal touch appears to be consistently associated with significant changes in the epigenetic status of genes involved in behavioral and stress regulation (eg, NR3C1 , SLC6A4 , OXTR ).…”

“…In the reviewed studies, different conceptualizations (and the related measures) of maternal caregiving behavior emerged as significantly associated with the DNA methylation status investigated [38][39][40][41][42][43][44][45] and/or as a significant buffering proxy to protect infants from detrimental consequences of adversity exposures earlier in life. 10,36,37 Among different maternal caregiving displays, maternal touch appears to be consistently associated with significant changes in the epigenetic status of genes involved in behavioral and stress regulation (eg, NR3C1, SLC6A4, OXTR). It should be noted that maternal touch presents individual differences in the amount and quality across different species 51,52 and a specific quality of maternal touch with infants and children, namely affectionate touch, is present in different animals as well as in humans and it appears to be physiologically underpinned by specific sensory fibers, namely the C-tactile fibers.…”

“…8,9 This research is providing unprecedented information on the biochemical pathways through which early adverse experiences are embedded in the developmental trajectories of an individual. Nonetheless, recent studies [10][11][12] highlighted that early exposures to protective environments (specifically the quality of maternal behavior) could also have a significant impact on epigenetic regulation of genes implicated in behavioral, cognitive and socio-emotional development. Although epigenetic vestiges of maternal caregiving are well supported by animal studies, 7,[12][13][14][15] more efforts are still needed in human research.…”