Metabolic Inheritance and the Competition for Calories between Mother and Fetus

Abstract

During the prenatal period, maternal and fetal cells compete for calories and nutrients. To ensure the survival of the mother and development of the fetus, the prenatal hormonal milieu alters the competitive environment via metabolic perturbations (e.g., insulin resistance). These perturbations increase maternal caloric consumption and engender increments in both maternal fat mass and the number of calories captured by the fetus. However, a mother’s metabolic and behavioral phenotypes (e.g., physical activity levels) and her external environment (e.g., food availability) can asymmetrically impact the competitive milieu, leading to irreversible changes in pre- and post-natal development—as exhibited by stunting and obesity. Therefore, the interaction of maternal metabolism, behavior, and environment impact the competition for calories—which in turn creates a continuum of health trajectories in offspring. In sum, the inheritance of metabolic phenotypes offers a comprehensive and consilient explanation for much of the increase in obesity and T2DM over the past 50 years in human and non-human mammals.

Challenging the utility of polygenic scores for social science: Environmental confounding, downward causation, and unknown biology

“…These non-genetic processes of inheritance and evolution are known as "maternal and grandmaternal effects" and are wellestablished across species (Bateson et al, 2004;Gluckman, Hanson, Cooper, & Thornburg, 2008;Maestripieri & Mateo, 2009). For example, stunting and pediatric obesity are caused by adverse intrauterine environmentsindependent of genotype (Archer, 2015a(Archer, , 2015b(Archer, , 2015c(Archer, , 2015dArcher et al, 2023;Archer & McDonald, 2017;Archer et al, 2018). In other words, starve any pregnant mammal and she will abort, or bear stunted offspringindependent of her genome.…”

“…Therefore, the greater phenotypic variability of fraternal twins is due to differences in gene expression engendered by different cells (eggs) acting in concert with inter-twin differences in both genotype and prenatal environments. Yet despite the extreme variability in the developmental competence (oocyte quality; e.g., mitochondrial content) of every female's population of eggs (Santos, El Shourbagy, & St John, 2006;Wang & Moley, 2010;Zhang et al, 2020;Zhou et al, 2020) and the irreversible impact of the intrauterine environment on development (Archer, 2015a(Archer, , 2015b(Archer, , 2015c(Archer, , 2015dArcher, Lavie, Dobersek, & Hill, 2023), the functional distinction between cellular, genetic, and environmental (in utero) inheritance is absent in 'twin-studies,' heritability statistics, and polygenic scores (PGSs).…”