Abstract
Gestational hypertensive disorders continue to threaten the well-being of pregnant women and their offspring. The only current definitive treatment for gestational hypertensive disorders is delivery of the fetus. The optimal timing of delivery remains controversial. Currently, the available clinical tools do not allow for assessment of fetal stress in its early stages. Placental insufficiency and fetal growth restriction secondary to gestational hypertensive disorders have been shown to have long-term impacts on offspring health even into their adulthood, becoming one of the major focuses of research in the field of developmental origins of health and disease. Fetal reprogramming was introduced to describe the long-lasting effects of the toxic intrauterine environment on the growing fetus. With the advent of high-throughput sequencing, there have been major advances in research attempting to quantify fetal reprogramming. Moreover, genes that are found to be differentially expressed as a result of fetal reprogramming show promise in the development of transcriptional biomarkers for clinical use in detecting fetal response to placental insufficiency. In this review, we will review key pathophysiology in the development of placental insufficiency, existing literature on high-throughput sequencing in the study of fetal reprogramming, and considerations regarding research design from our own experience.
Highlights
Despite progress in global efforts to reduce pregnancy-related maternal and neonatal mortality, pregnancy-related vascular disorders continue to prevail and negatively impact maternal–fetal health [1]
We demonstrated that SLC25A42 was differentially expressed when comparing the placental insufficiency group to the preeclampsia and the control groups, but not when comparing the preeclampsia group to the control group
RT-PCR, and used molecular biology techniques to confirm regulation of two gene targets, CSF1 and ITGAM, by miR-210-5p [38]. Both genes are involved in macrophage activation, and were found to only be differentially regulated in the group with preeclampsia and fetal growth restriction (FGR), suggesting that a macrophage-related inflammatory pathway may be involved in placental insufficiency [39]
Summary
Despite progress in global efforts to reduce pregnancy-related maternal and neonatal mortality, pregnancy-related vascular disorders continue to prevail and negatively impact maternal–fetal health [1]. It is generally accepted that abnormal placental vasculogenesis and angiogenesis are responsible for the development of increased vascular resistance, resulting in a spectrum of vascular disorders of pregnancy ranging from asymptomatic gestational hypertension to life-threatening eclampsia. Myometrial spiral artery remodeling occurs during the second trimester, with relaxation of the high-resistant coiled vessels promoting blood flow to the maternal–fetal interface in the villi, allowing proper gas exchange and nutrient delivery. Further neovascularization and local tissue remodeling result in increased blood flow to the region, creating a favorable system to allow rapid fetal growth in the third trimester. When this process is interrupted, increased resistance persists in the placental vasculature, causing maternal hypertension and end-organ damage. There are multiple studies denoting that abnormal white matter development is associated with FGR [14,15,16]
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