Maternal Metabolic Health, Lifestyle, and Environment – Understanding How Epigenetics Drives Future Offspring Health

Abstract

The incidence of metabolic disorders such as obesity and type two diabetes (T2DM) continues to increase worldwide, and their onset is often attributed to adherence to a western diet and a sedentary lifestyle. However, a large variability exists in one's likelihood of developing metabolic dysregulation, illustrating that our understanding of heritability patterns remains poorly understood. Diabetes and obesity are multifactorial diseases, and their onset is influenced by both genetic and environmental factors. Genome-wide association studies reported a number of alterations in the coding sequence associated with the onset of T2DM and obesity. However, these genes explain only a fraction of the cases, leaving the majority unaccounted for. The missing heritability question implies that other factors are responsible for the onset and development of the disease. Given that the developing fetus is susceptible to the maternal environment, a growing body of evidence demonstrates that maternal metabolic characteristics as well as disruptions to the prenatal environment may induce long-term genetic, phenotypic, and physiologic adaptations in the developing fetus, which could have a permanent effect on its future health. This phenomenon is known as developmental programming and is mediated through epigenetic modifications, which include modulation of gene expression that do not alter the original deoxyribonucleic (DNA) sequence. Epigenetic modifications are capable of changing gene expression in metabolism-related genes and are accomplished through DNA methylation, histone acetylation, and ribonucleic acid (RNA) mechanisms. In this review, we discuss maternal metabolic factors such as obesity, dyslipidemia, and gestational diabetes (GDM) that lead to epigenetic changes in the offspring and predispose future generations to metabolic abnormalities. We will also describe the association between maternal lifestyle factors and exposure to toxins with epigenetic modulations in the offspring. Lastly, we will provide a brief review of the possibility of using epigenetics as potential interventions and therapeutic modalities to help with early diagnosis and prevention of metabolic disorders.

Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs

“…Both oocyte quality and uterine environment have contributions to adult diseases that may be mediated by epigenetic modifications ( 6 ). Our recent study demonstrates that disturbed methylation in oocytes caused by uterine undernourishment can be partly transmitted to F2 oocytes via female, which may play a key role in the transgenerational inheritance of metabolic disorders ( 7 ).…”

Gluco-regulation & type 2 diabetes: entrenched misconceptions updated to new governing principles for gold standard management

“…It has long been understood that prenatal exposure to maternal conditioning influences the risk for obesity and T2D later in life ( reviewed by these authors [SSS] in Amrom & Schwartz 2022 ( 49 ). The subsequent development of genetic tools led to the discovery that epigenetic programming is behind this phenomenon, allowing for phenotypic plasticity and adaptation ( 50 ).…”

On the Role of Seminal Fluid Protein and Nucleic Acid Content in Paternal Epigenetic Inheritance

“…Changes in the maternal environment can dramatically affect the phenotype of the offspring, as we have learned a lot from the outcome of research on maternal effects [ 141 , 142 , 143 , 144 , 145 , 146 ]. Seminal fluid is transferred to females along with sperm during mating, and its contents are capable of inducing physiological and behavioral changes in female [ 54 , 147 , 148 , 149 , 150 , 151 , 152 ].…”