Epigenetic processes during preeclampsia and effects on fetal development and chronic health

Abstract

Preeclampsia (PE), the leading cause of maternal and fetal morbidity and mortality, is associated with poor fetal growth, intrauterine growth restriction (IUGR) and low birth weight (LBW). Offspring of women who had PE are at increased risk for cardiovascular (CV) disease later in life. However, the exact etiology of PE is unknown. Moreover, there are no effective interventions to treat PE or alleviate IUGR and the developmental origins of chronic disease in the offspring. The placenta is critical to fetal growth and development. Epigenetic regulatory processes such as histone modifications, microRNAs and DNA methylation play an important role in placental development including contributions to the regulation of trophoblast invasion and remodeling of the spiral arteries. Epigenetic processes that lead to changes in placental gene expression in PE mediate downstream effects that contribute to the development of placenta dysfunction, a critical mediator in the onset of PE, impaired fetal growth and IUGR. Therefore, this review will focus on epigenetic processes that contribute to the pathogenesis of PE and IUGR. Understanding the epigenetic mechanisms that contribute to normal placental development and the initiating events in PE may lead to novel therapeutic targets in PE that improve fetal growth and mitigate increased CV risk in the offspring.

Genetic markers of the risk of fetal growth retardation in pregnant women with preeclampsia

“…Для полиморфизма GWAS-значимых генов -кандидатов АГ, показавших статистически значимые ассоциации с развитием ЗРП у беременных с ПЭ, был изучен регуляторный потенциал по материалам проекта HaploReg v4.1 2 , проведена оценка взаимосвязи рассматриваемых локусов с экспрессионной и транскрипционной активностью генов с использованием международной базы данных GTExPortal 3 .…”

“…Ежегодно ПЭ становится причиной 60 000 материнских смертей и более чем 500 000 случаев преждевременных родов во всем мире [2]. Нарушение плацентации на ранних сроках беременности, а также родоразрешение вне зависимости от срока гестации как единственный эффективный метод лечения ПЭ сопряжено с формированием задержки роста плода (ЗРП) и низкой массой плода при рождении [3]. ЗРП оказывает значительное влияние на структуру перинатальной заболеваемости и смертности, основными причинами которых является респираторный дистресссиндром, бронхолегочная дисплазия, некротизирующий энтероколит, сепсис и др., а также повышает риск развития метаболического синдрома, сердечно-сосудистой патологии, нервно-психологических и эндокринных нарушений в отдаленном будущем у детей с ЗРП [2,4,5].…”

“…HaploReg v4.1. Available at: https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php 3. GTExPortal.…”

N6-methyladenosine modifications in maternal-fetal crosstalk and gestational diseases

“…The placenta acts as a medium for pregnant women and fetuses, enabling the exchange of nutrients, gas and also waste productions, protecting fetuses from maternal immune attack, and also secreting hormones and factors to support fetal growth. The defects of placentation will result in a range of gestational diseases ( Jauniaux et al, 2006 ; Ananth, 2014 ; Roberts, 2014 ; Ashraf et al, 2021 ), such as miscarriage, preterm birth, gestational diabetes mellitus, pre-eclampsia and fetal growth restriction. Placental development during the whole gestation involves a variety of cellular function changes and transformations ( Caniggia et al, 2000 ; Pringle et al, 2010 ).…”

Role of microRNAs regulating trophoblast cell function in the pathogenesis of pre‑eclampsia (Review)

“…The regulation of ncRNAs alters gene activity, thereby regulating gene expression and transcription, as well as chromatin structure, epigenetic memory and protein translation ( 11 ). Epigenetic changes, in particular altered expression of certain miRs, may play key roles in placental-related disease such as PE and IUGR, which cause changes in placental gene expression, mediate downstream effects and promote development of placental dysfunction ( 12 ). Some lncRNAs and circRNAs inhibit the function of miRs by binding to other miRs, thereby acting as miR sponges ( 13 ).…”