Placental proteome in late‑onset of fetal growth restriction

Abstract

Fetal growth restriction (FGR) occurs when the fetus does not reach its genetically programmed intrauterine potential for growth and affects ~5-10% of pregnancies. This condition is one of the leading causes of perinatal mortality and morbidity associated with obstetric and neonatal complications. Placental dysfunction in FGR causes an impairment in the transfer of nutrients and oxygen from the mother to the developing fetus. Maternal adaptations to placental insufficiency may also play a role in the pathophysiology of FGR. The present study aimed to compare the proteome of the placentas of 18 women with the physiological course of pregnancy and eutrophic fetus [estimated fetal weight (EFW) >10th percentile; control group] and 18 women with late FGR (EFW <10th percentile) diagnosed after 32 weeks of pregnancy, according to the Delphi consensus (study group). The U. Mann-Whitney test was used to compare two independent groups. The R. Spearman correlation coefficient significance test was used to assess the existence of a relationship between the analyzed measurable parameters. P<0.05 was considered to indicate a statistically significant difference. The tests showed the presence of 356 different proteins which were responsible for the regulation of gene transcription control, inhibiting the activity of proteolytic enzymes, regulation of trophoblast proliferation and angiogenesis and inflammatory response. In the FGR placental proteome, other detected proteins were mostly involved in response to oxidative stress, cellular oxidation and detoxication, apoptosis, hemostatic and catabolic processes, energy transduction protein interactions, cell proliferation, differentiation and intracellular signaling. The present study used chromatographic mass-spectrometry to compare the placental proteome profiles in pregnancies complicated by late-onset FGR and normal pregnancy. Comparative analysis of proteomes from normal and FGR placentas showed significant differences. Further research is needed to clarify maternal and fetal adaptations to FGR.

Human cord plasma proteomic analysis reveals sexually dimorphic proteins associated with intrauterine growth restriction

“…Several proteins identified in our cohort (e.g., CAT, HBG1, PKM, PNP, S100A8, IDH1) were previously reported to be associated with fetal growth restriction using either maternal or cord plasma [12,15,21]. IUGR is associated with impaired nutrient and/or oxygen delivery that may leave the mononuclear cells in cord plasma, fetal organs and placenta more susceptible to damage and leakage of cytosolic proteins consistent with the increased levels of proteins such as CAT in IUGR cord plasma [12,15,24,25]. In contrast to our findings, previous IUGR [7,22,23].…”

“…Molecular profiling of maternal plasma have revealed alterations in lipid metabolism, activation of pro-coagulant, reactive oxygen species, nutrient transport, energy metabolism, and immune-mediated chronic inflammation pathways [7][8][9][10][11]. In the IUGR placental proteome, most detected proteins are related to oxidative stress, cellular oxidation and detoxication, apoptosis, angiogenesis, energy transduction, cell proliferation, differentiation, and intracellular signaling [12][13][14][15].…”

Comparative Analysis of the Placental Microbiome in Pregnancies with Late Fetal Growth Restriction versus Physiological Pregnancies

“…The results of the study were obtained from 18 placentas taken from women with fetal growth disorders and from 18 control placentas. The clinical characteristics along with anthropometric measurements of mothers and their newborns are presented in our previous study, as in Table 1 [ 27 ].…”

Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae

“…During a routine follow-up of pregnant women or around birth, various biosamples can be collected non-invasively. Recent human studies have been performed in placenta [ 67 , 68 , 69 ], maternal [ 37 , 70 , 71 , 72 ] or umbilical cord blood [ 70 , 71 ], and maternal feces [ 72 ]. Multi-omics analyses help to develop hypotheses about the pathophysiological alterations occurring in the IUGR mother and placenta, as well as the adaptions that take place in the IUGR fetus.…”

“…Oxidative stress is generally high in the placenta due to its high mitochondrial activity, which leads to endogenous ROS production. Placental proteomics uncovered that a large amount of the proteins differentially expressed in placentas of late-onset IUGR pregnancies are involved in the oxidative stress response [ 67 ]. Oxidative stress even appears to precede clinical features, as an increase in maternal urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) concentrations at 12 weeks gestation was associated with an increased risk for giving birth to an infant with a birth weight below the tenth percentile [ 75 ].…”