Multi-omics-based mapping of decidualization resistance in patients with a history of severe preeclampsia.

Endometrial decidualization resistance (DR) is implicated in various gynecological and obstetric conditions. Here, using a multi-omic strategy, we unraveled the cellular and molecular characteristics of DR in patients who have suffered severe preeclampsia (sPE). Morphological analysis unveiled significant glandular anatomical abnormalities, confirmed histologically and quantified by the digitization of hematoxylin and eosin-stained tissue sections.

Fluoride-related changes in the fetal cord blood proteome; a pilot study.

Background: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA.

Objective: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.

Gravidity influences distinct transcriptional profiles of maternal and fetal placental macrophages at term.

Introduction: Maternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Maternal reproductive history is associated with differential risk of pregnancy complications. The molecular phenotypes and roles of these distinct monocyte/macrophage populations and the influence of gravidity on these phenotypes has not been systematically investigated.

Fluoride-related changes in the fetal cord blood proteome; a pilot study.

Background: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride affects human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in Northern California with either high or low fluoride exposure, as identified by maternal serum fluoride concentrations.

Objective: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women living in Northern California.

Distinct transcriptional profiles of maternal and fetal placental macrophages at term are associated with gravidity.

Maternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Little is known regarding the molecular phenotypes and roles of these distinct monocyte/macrophage populations. Here, we used RNA sequencing to investigate the transcriptional profiles of MIMs and HBCs in six normal term pregnancies.

Perfluorooctanoic acid induces transcriptomic alterations in second trimester human cytotrophoblasts.

Poly- and perfluroroalkylated substances (PFAS) are a major class of surfactants used in industry applications and consumer products. Despite efforts to reduce the usage of PFAS due to their environmental persistence, compounds such as perfluorooctanoic acid (PFOA) are widely detected in human blood and tissue. Although growing evidence supports that prenatal exposures to PFOA and other PFAS are linked to adverse pregnancy outcomes, the target organs and pathways remain unclear.

Proteomic analyses of primary human villous trophoblasts exposed to flame retardant BDE-47 using SWATH-MS.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling.

Vedolizumab Antagonizes MAdCAM-1-Dependent Human Placental Cytotrophoblast Adhesion and Invasion In Vitro.

Background: Anti-α4β7 (Vedolizumab) treats inflammatory bowel disease (IBD) by blocking the interaction between integrin α4β7 on leukocytes and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) on the gut endothelium. Women with IBD often require continuing biologic therapy during pregnancy to avoid disease flare. To date, there have been no reports of an increase in adverse events with Vedolizumab use during pregnancy.

RNA profiling of laser microdissected human trophoblast subtypes at mid-gestation reveals a role for cannabinoid signaling in invasion.

Human placental architecture is complex. Its surface epithelium, specialized for transport, forms by fusion of cytotrophoblast progenitors into multinucleated syncytiotrophoblasts. Near the uterine surface, these progenitors assume a different fate, becoming cancer-like cells that invade its lining and blood vessels.

Global proteomic analyses of human cytotrophoblast differentiation/invasion.

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A crucial hurdle in pregnancy is the ability of these cells to migrate, invade and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus.

Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease.

The human placenta and its specialized cytotrophoblasts rapidly develop, have a compressed lifespan, govern pregnancy outcomes, and program the offspring's health. Understanding the molecular underpinnings of these behaviors informs development and disease. Profiling the extraembryonic epigenome and transcriptome during the 2nd and 3rd trimesters revealed H3K9 trimethylation overlapping deeply DNA hypomethylated domains with reduced gene expression and compartment-specific patterns that illuminated their functions.

Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62).

Gravidity-dependent associations between interferon response and birth weight in placental malaria.

Background: Maternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal-fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses.

Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation.

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal-fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014-16).

Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum.

In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.

Trisomy 21 is Associated with Caspase-2 Upregulation in Cytotrophoblasts at the Maternal-Fetal Interface.

Impaired placentation is implicated in poor perinatal outcomes associated with Trisomy 21. Earlier studies revealed abnormal cytotrophoblast differentiation along the invasive pathway as a contributing mechanism. To further elucidate the causes, we evaluated Caspase-2 expression at the protein level (immunolocalization and immunoblot) in samples from Trisomy 21 (n = 9) and euploid (n = 4) age-matched placentas.

Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort.

Background: There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes.

Methods: This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed.

Differential Activation of Fetal Hofbauer Cells in Primigravidas Is Associated with Decreased Birth Weight in Symptomatic Placental Malaria.

Background: Placental malaria is a leading global cause of low birth weight neonates, especially in first-time mothers. To better understand the role of innate immunity in placental malaria, we investigated the relationships between histopathological markers of placental malaria, fetal and maternal macrophage responses, and perinatal outcomes in a cross-sectional case control study of pregnant women presenting with symptomatic malaria at the time of delivery.

Results: Primigravidas showed increased hemozoin deposition in placental villi (=0.

Placental Structure in Preterm Birth Among HIV-Positive Versus HIV-Negative Women in Kenya.

Background: Preterm birth (PTB) is a major cause of infant morbidity and mortality in developing countries. Recent data suggest that in addition to Human Immunodeficiency Virus (HIV) infection, use of antiretroviral therapy (ART) increases the risk of PTB. As the mechanisms remain unexplored, we conducted this study to determine whether HIV and ART were associated with placental changes that could contribute to PTB.

Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts.

Despite gradual legislative efforts to phase out flame retardants (FRs) from the marketplace, polybrominated diphenyl ethers (PBDEs) are still widely detected in human maternal and fetal tissues, eg, placenta, due to their continued global application in consumer goods and inherent biological persistence. Recent studies in rodents and human placental cell lines suggest that PBDEs directly cause placental toxicity. During pregnancy, trophoblasts play key roles in uterine invasion, vascular remodeling, and anchoring of the placenta-fetal unit to the mother.