Progress in the understanding of the etiology and predictability of fetal growth restriction

Abstract

Fetal growth restriction (FGR) is defined as the failure of fetus to reach its growth potential for various reasons, leading to multiple perinatal complications and adult diseases of fetal origins. Shallow extravillous trophoblast (EVT) invasion-induced placental insufficiency and placental dysfunction are considered the main reasons for idiopathic FGR. In this review, first we discuss the major characteristics of anti-angiogenic state and the pro-inflammatory bias in FGR. We then elaborate major abnormalities in placental insufficiency at molecular levels, including the interaction between decidual leukocytes and EVT, alteration of miRNA expression and imprinted gene expression pattern in FGR. Finally, we review current animal models used in FGR, an experimental intervention based on animal models and the progress of predictive biomarker studies in FGR. Free Chinese abstract: A Chinese translation of this abstract is freely available at http://www.reproduction-online.org/content/153/6/ R227/suppl/DC1. Reproduction (2017) 153 R227-R240

Porphyromonas gingivalisand adverse pregnancy outcome

“…P. gingivalis-induced FGR is indeed associated with an increased placental expression of TH1-type cytokines: IFN-γ, IL-2, and IL-12 with a concurrent reduction in TH2 type IL-10 and TGF-β2 [57]. It should be noted that FGR is a syndrome with multiple pathologic etiologies [14,58]. Underlying causes of FGR include inflammation from unknown causes or secondary to hematogenous infection, as well as underlying vasculopathies such as poorly remodeled uterine arteries or abnormal placental angiogenesis [58].…”

“…Taken together, this suggests that A7436, by itself, is unlikely to trigger the overt inflammatory responses that initiate spontaneous preterm labor [15]. Instead, the pathologic features observed with A7436 are more in line with implantation failure or poor placentation, which often occur with recurrent miscarriage, fetal growth restriction, or preeclampsia [14,75,104,105].…”

“…Experimental infection in various animal models confirms that invasion of the uterine compartment by P. gingivalis produces a diverse array of APO, including utero-placental pathology, enhanced expression of pro-T helper (TH)1 type cytokines (IFN-γ, IL-2, IL-12, and TNF-α), fetal growth restriction (FGR), and spontaneous preterm delivery [12][13][14][15]. Since these outcomes are manifestations of different pathologic mechanisms within the fetal compartment, it may seem somewhat perplexing that one organism could be responsible for all of these complications.…”

“…Since these outcomes are manifestations of different pathologic mechanisms within the fetal compartment, it may seem somewhat perplexing that one organism could be responsible for all of these complications. For example, FGR can be a sequela of abnormal placentation or placental angiogenesis, and can accompany severe or early onset preeclampsia [14]. Inflammation associated with FGR or preeclampsia is usually maternal in origin [14].…”

“…For example, FGR can be a sequela of abnormal placentation or placental angiogenesis, and can accompany severe or early onset preeclampsia [14]. Inflammation associated with FGR or preeclampsia is usually maternal in origin [14]. On the other hand, preterm labor is a complication of overt inflammation that begins in the fetal sac and is usually initiated by activation of toll-like receptors or inflammasomes [15,16].…”