Abnormal Placentation Associated with Infertility as a Marker of Overall Health

Sundheimer, L.W.; Pisarska, Margareta D.

doi:10.1055/s-0037-1603570

Cited by 16 publications

(12 citation statements)

References 185 publications

(208 reference statements)

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“…In humans and other placental mammals, the fertilized egg gives rise to both the fetus and the placenta. Placentation in the first trimester can impact fetal growth, and abnormal placentation can lead to more pronounced effects complicating pregnancy including intrauterine growth restriction (IUGR) which results in very low birth weight infants, a sexually dimorphic outcome [ 1 – 4 ]. The process of placentation occurs throughout the first trimester of pregnancy, whereby the outer cells of the blastocyst (the trophoblast cells) invade the maternal tissue and develop into the placenta.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the late first trimester human placenta transcriptome

et al. 2018

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BackgroundDevelopment of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood.MethodsRNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males). Gene enrichment analysis was performed to find enriched canonical pathways and gene ontologies in the first trimester. DESeq2 was used to find sexually dimorphic gene expression. Patient demographics were analyzed for sex differences in fetal weight at time of chorionic villus sampling and birth.ResultsRNA-sequencing analyses detected 14,250 expressed genes, with chromosome 19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes) and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched genes as well as histone-coding genes were identified to be unique to the first trimester and common to both sexes. Further, we identified 58 genes with significantly different expression between males and females: 25 X-linked, 15 Y-linked, and 18 autosomal genes. Genes that escape X inactivation were highly represented (59.1%) among X-linked genes upregulated in females. Many genes differentially expressed by sex consisted of X/Y gene pairs, suggesting that dosage compensation plays a role in sex differences. These X/Y pairs had roles in parallel, ancient canonical pathways important for eukaryotic cell growth and survival: chromatin modification, transcription, splicing, and translation.ConclusionsThis study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long-term adult health.Electronic supplementary materialThe online version of this article (10.1186/s13293-018-0165-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Sex differences in the late first trimester human placenta transcriptome

et al. 2018

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“…5 ). In addition, XCL2, the X-C motif chemokine ligand 2, which is a member of the C-chemokine superfamily and functions in inflammatory and immunological responses, inducing leukocyte migration and activation [ 52 ], could be another marker for EPL. Recently, three developmental branches in which dNKp differentiates into dNK1 cells (Path 1) and into two distinct branches of dNK2 and dNK3 cells (Path 2 and Path 3) have been proposed with high-resolution pseudotime prediction [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

Characterization of placental and decidual cell development in early pregnancy loss by single-cell RNA sequencing

Zheng

Pan²,

Xia³

et al. 2022

Cell Biosci

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Background Early pregnancy loss (EPL) presents as sporadic or recurrent miscarriage during the first trimester. In addition to chromosomal defects, EPL may result from impairment of the placental-decidual interface at early gestational age due to gene-environmental interactions. Methods To better understand the pathogenesis associated with this impairment, cell development in chorionic villi and decidua of different forms of EPL (sporadic or recurrent) was investigated with single-cell RNA sequencing and compared to that of normal first-trimester tissue. Results Unique gene expression signatures were obtained for the different forms of EPL and for normal tissue and the composition of placental and decidual cell clusters in each form was established. In particular, the involvement of macrophages in the EPL phenotypes was identified revealing an immunoactive state. Conclusion Differential gene expression and unique marker genes among cell clusters from chorionic villi and decidua of miscarried and normal pregnancies, may lead to identification of biomarker for EPL.

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“…Sundheimer and Pisarska explain that the size of the placental bed and successful trophoblast invasion and spiral artery remodeling determine maternal blood flow. With these premises, abnormal placentation associated with infertility can represent a consequent marker of overall health for both the mother and her offspring [ 134 ]. It has been well known for a long time that inadequate trophoblast invasion and poor spiral artery remodeling may cause reduced vascular perfusion in pregnancy [ 135 ].…”

Section: Metabolic and Cardiovascular Consequences Of Placental Dysregulation In Mothers Following Artmentioning

confidence: 99%

Placental Dysfunction in Assisted Reproductive Pregnancies: Perinatal, Neonatal and Adult Life Outcomes

Manna

Lacconi

Rizzo

et al. 2022

IJMS

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Obstetric and newborn outcomes of assisted reproductive technology (ART) pregnancies are associated with significative prevalence of maternal and neonatal adverse health conditions, such as cardiovascular and metabolic diseases. These data are interpreted as anomalies in placentation involving a dysregulation of several molecular factors and pathways. It is not clear which extent of the observed placental alterations are the result of ART and which originate from infertility itself. These two aspects probably act synergically for the final obstetric risk. Data show that mechanisms of inappropriate trophoblast invasion and consequent altered vascular remodeling sustain several clinical conditions, leading to obstetric and perinatal risks often found in ART pregnancies, such as preeclampsia, fetal growth restriction and placenta previa or accreta. The roles of factors such as VEGF, GATA3, PIGF, sFLT-1, sEndoglin, EGFL7, melatonin and of ART conditions, such as short or long embryo cultures, trophectoderm biopsy, embryo cryopreservation, and supraphysiologic endometrium preparation, are discussed. Inflammatory local conditions and epigenetic influence on embryos of ART procedures are important research topics since they may have important consequences on obstetric risk. Prevention and treatment of these conditions represent new frontiers for clinicians and biologists involved in ART, and synergic actions with researchers at molecular levels are advocated.

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Abnormal Placentation Associated with Infertility as a Marker of Overall Health

Cited by 16 publications

References 185 publications

Sex differences in the late first trimester human placenta transcriptome

Sex differences in the late first trimester human placenta transcriptome

Characterization of placental and decidual cell development in early pregnancy loss by single-cell RNA sequencing

Placental Dysfunction in Assisted Reproductive Pregnancies: Perinatal, Neonatal and Adult Life Outcomes

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