The placental gateway of maternal transgenerational epigenetic inheritance

Abstract

While much of our understanding of genetic inheritance is based on the genome of the organism, it is becoming clear that there is an ample amount of epigenetic inheritance, which though reversible, escapes erasing process during gametogenesis and goes on to the next generation. Several examples of transgenerational inheritance of epigenetic features with potential impact on embryonic development and subsequent adult life have come to light. In placental mammals, the placenta is an additional route for epigenetic information flow. This information does not go through any meiotic reprogramming and is, therefore, likely to have a more profound influence on the organism. This also has the implication of providing epigenetic instructions for several months, which is clearly a maternal advantage. Although less well-known, there is also an impact of the embryo in emitting genetic information to the maternal system that remains well beyond the completion of the pregnancy. In this review, we discuss several factors in the context of the evolution of this mammal-specific phenomenon, including genomic imprinting, micromosaicism, and assisted reproduction. We also highlight how this kind of inheritance might require attention in the modern lifestyle within the larger context of the evolutionary process.

The Attenuation of Trophoblast Invasion Caused by the Downregulation of EZH2 Is Involved in the Pathogenesis of Human Recurrent Miscarriage

“…Delicate control of trophoblast invasion is important for implantation, uterine spiral artery remodeling, and maternal-fetal communication 34 . Moreover, numerous studies have established a strong link between epigenetic regulation and placental trophoblast function by demonstrating the critical role of epigenetic regulators in maintaining a healthy pregnancy 8, 35, 36. In this study, we investigated the role of EZH2 in the invasiveness of trophoblast.…”

Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction

“…Epidemiologic studies have shown an intergenerational association of FGR: women who, themselves, were born with low birth weight are more likely to reproduce low birth weight offspring ( 73 – 75 ). Apart from genetic, familial, and socioeconomic predispositions, complex molecular processes, such as genetic imprinting, microchimerism, and epigenetic modifications, are involved ( 76 , 77 ), and this results from early neonatal life onward in the disruption of endocrine and metabolic systems ( 78 , 79 ) together with permanent dysfunctions of vital organ systems ( 80 , 81 ), such as the kidneys ( 82 , 83 ), the heart and blood circulation ( 76 , 84 , 85 ), the endothelium ( 86 ), and the immune system ( 80 ). In the long run, these systemic dysfunctions predispose to early onset adult disease ( 87 ).…”

The Placenta as a Target of Epigenetic Alterations in Women with Gestational Diabetes Mellitus and Potential Implications for the Offspring

“…These stable changes include several mechanisms such as DNA and RNA methylation, chromatin remodeling, histone modifications, and the expression of noncoding RNAs (ncRNAs). The placenta presents its own epigenetic programing during gestation [ 20 ], affecting both the pregnant woman’s metabolism and fetal development. Thus, epigenetic alterations will likely induce pregnancy complications and disease susceptibility for both [ 21 ] ( Figure 2 ).…”

“…The placenta favors epigenetic flow during gestation [ 20 ], controlling both the pregnant woman’s metabolism and fetal development. We define this epigenetic flow as all epigenetic alterations induced by the mother’s condition, reaching the fetus through the placenta.…”