Human Term Placenta Research Articles

Lipid Aldehydes 4-Hydroxynonenal and 4-Hydroxyhexenal Exposure Differentially Impact Lipogenic Pathways in Human Placenta.

Long chain polyunsaturated fatty acids (LCPUFAs), such as the omega-6 (n-6) arachidonic acid (AA) and n-3 docosahexanoic acid (DHA), have a vital role in normal fetal development and placental function. Optimal supply of these LCPUFAs to the fetus is critical for improving birth outcomes and preventing programming of metabolic diseases in later life. Although not explicitly required/recommended, many pregnant women take n-3 LCPUFA supplements. Oxidative stress can cause these LCPUFAs to undergo lipid peroxidation, creating toxic compounds called lipid aldehydes. These by-products can lead to an inflammatory state and negatively impact tissue function, though little is known about their effects on the placenta. Placental exposure to two major lipid aldehydes, 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE), caused by peroxidation of the AA and DHA, respectively, was examined in the context of lipid metabolism. We assessed the impact of exposure to 25 μM, 50 μM and 100 μM of 4-HNE or 4-HHE on 40 lipid metabolism genes in full-term human placenta. 4-HNE increased gene expression associated with lipogenesis and lipid uptake (ACC, FASN, ACAT1, FATP4), and 4-HHE decreased gene expression associated with lipogenesis and lipid uptake (SREBP1, SREBP2, LDLR, SCD1, MFSD2a). These results demonstrate that these lipid aldehydes differentially affect expression of placental FA metabolism genes in the human placenta and may have implications for the impact of LCPUFA supplementation in environments of oxidative stress.

Is there a placental microbiota? A critical review and re-analysis of published placental microbiota datasets

The existence of a placental microbiota is debated. The human placenta has historically been considered sterile and microbial colonization was associated with adverse pregnancy outcomes. Yet, recent DNA sequencing investigations reported a microbiota in typical human term placentas. However, this detected microbiota could represent background DNA or delivery-associated contamination. Using fifteen publicly available 16S rRNA gene datasets, existing data were uniformly re-analyzed with DADA2 to maximize comparability. While Amplicon Sequence Variants (ASVs) identified as Lactobacillus, a typical vaginal bacterium, were highly abundant and prevalent across studies, this prevalence disappeared after applying likely DNA contaminant removal to placentas from term cesarean deliveries. A six-study sub-analysis targeting the 16S rRNA gene V4 hypervariable region demonstrated that bacterial profiles of placental samples and technical controls share principal bacterial ASVs and that placental samples clustered primarily by study origin and mode of delivery. Contemporary DNA-based evidence does not support the existence of a placental microbiota.ImportanceEarly-gestational microbial influences on human development are unclear. By applying DNA sequencing technologies to placental tissue, bacterial DNA signals were observed, leading some to conclude that a live bacterial placental microbiome exists in typical term pregnancy. However, the low-biomass nature of the proposed microbiome and high sensitivity of current DNA sequencing technologies indicate that the signal may alternatively derive from environmental or delivery-associated bacterial DNA contamination. Here we address these alternatives with a re-analysis of 16S rRNA gene sequencing data from 15 publicly available placental datasets. After identical DADA2 pipeline processing of the raw data, subanalyses were performed to control for mode of delivery and environmental DNA contamination. Both environment and mode of delivery profoundly influenced the bacterial DNA signal from term-delivered placentas. Aside from these contamination-associated signals, consistency was lacking across studies. Thus, placentas delivered at term are unlikely to be the original source of observed bacterial DNA signals.

The immune checkpoint molecule, VTCN1/B7-H4, guides differentiation and suppresses proinflammatory responses and MHC class I expression in an embryonic stem cell-derived model of human trophoblast.

The placenta acts as a protective barrier to pathogens and other harmful substances present in the maternal circulation throughout pregnancy. Disruption of placental development can lead to complications of pregnancy such as preeclampsia, intrauterine growth retardation and preterm birth. In previous work, we have shown that expression of the immune checkpoint regulator, B7-H4/VTCN1, is increased upon differentiation of human embryonic stem cells (hESC) to an in vitro model of primitive trophoblast (TB), that VTCN1/B7-H4 is expressed in first trimester but not term human placenta and that primitive trophoblast may be uniquely susceptible to certain pathogens. Here we report on the role of VTCN1 in trophoblast lineage development and anti-viral responses and the effects of changes in these processes on major histocompatibility complex (MHC) class I expression and peripheral NK cell phenotypes.

Benzo(a)pyrene and Cerium Dioxide Nanoparticles in Co-Exposure Impair Human Trophoblast Cell Stress Signaling

Human placenta is a multifunctional interface between maternal and fetal blood. Studying the impact of pollutants on this organ is crucial because many xenobiotics in maternal blood can accumulate in placental cells or pass into the fetal circulation. Benzo(a)pyrene (BaP) and cerium dioxide nanoparticles (CeO2 NP), which share the same emission sources, are found in ambient air pollution and also in maternal blood. The aim of the study was to depict the main signaling pathways modulated after exposure to BaP or CeO2 NP vs. co-exposure on both chorionic villi explants and villous cytotrophoblasts isolated from human term placenta. At nontoxic doses of pollutants, BaP is bioactivated by AhR xenobiotic metabolizing enzymes, leading to DNA damage with an increase in γ-H2AX, the stabilization of stress transcription factor p53, and the induction of its target p21. These effects are reproduced in co-exposure with CeO2 NP, except for the increase in γ-H2AX, which suggests a modulation of the genotoxic effect of BaP by CeO2 NP. Moreover, CeO2 NP in individual and co-exposure lead to a decrease in Prx-SO3, suggesting an antioxidant effect. This study is the first to identify the signaling pathways modulated after co-exposure to these two pollutants, which are common in the environment.

Assessment of the role of nucleoside transporters, P-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in the placental transport of entecavir using in vitro, ex vivo, and in situ methods

The nucleoside analog entecavir (ETV) is a first-line pharmacotherapy for chronic hepatitis B in adult and pediatric patients. However, due to insufficient data on placental transfer and its effects on pregnancy, ETV administration is not recommended for women after conception. To expand knowledge of safety, we focused on evaluating the contribution of nucleoside transporters (NBMPR sensitive ENTs and Na+ dependent CNTs) and efflux transporters, P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), and multidrug resistance-associated transporter 2 (ABCC2), to the placental kinetics of ETV. We observed that NBMPR and nucleosides (adenosine and/or uridine) inhibited [3H]ETV uptake into BeWo cells, microvillous membrane vesicles, and fresh villous fragments prepared from the human term placenta, while Na+ depletion had no effect. Using a dual perfusion study in an open-circuit setup, we showed that maternal-to-fetal and fetal-to-maternal clearances of [3H]ETV in the rat term placenta were decreased by NBMPR and uridine. Net efflux ratios calculated for bidirectional transport studies performed in MDCKII cells expressing human ABCB1, ABCG2, or ABCC2 were close to the value of one. Consistently, no significant decrease in fetal perfusate was observed in the closed-circuit setup of dual perfusion studies, suggesting that active efflux does not significantly reduce maternal-to-fetal transport. In conclusion, ENTs (most likely ENT1), but not CNTs, ABCB1, ABCG2, and ABCC2, contribute significantly to the placental kinetics of ETV. Future studies should investigate the placental/fetal toxicity of ETV, the impact of drug-drug interactions on ENT1, and interindividual variability in ENT1 expression on the placental uptake and fetal exposure to ETV.

SLC20a1/PiT-1 is required for chorioallantoic placental morphogenesis.

The placenta mediates the transport of nutrients, such as inorganic phosphate (Pi), between the maternal and fetal circulatory systems. The placenta itself also requires high levels of nutrient uptake as it develops to provide critical support for fetal development. This study aimed to determine placental Pi transport mechanisms using in vitro and in vivo models. We observed that Pi (P33) uptake in BeWo cells is sodium dependent and that SLC20A1/Slc20a1 is the most highly expressed placental sodium-dependent transporter in mouse (microarray), human cell line (RT-PCR) and term placenta (RNA-seq), supporting that normal growth and maintenance of the mouse and human placenta requires SLC20A1/Slc20a1. Slc20a1 wild-type (Slc20a1+/+) and knockout (Slc20a1-/-) mice were produced through timed intercrosses and displayed yolk sac angiogenesis failure as expected at E10.5. E9.5 tissues were analyzed to test whether placental morphogenesis requires Slc20a1. At E9.5, the developing placenta was reduced in size in Slc20a1-/-. Multiple structural abnormalities were also observed in the Slc20a1-/-chorioallantois. We determined that monocarboxylate transporter 1 protein (MCT1+) cells were reduced in developing Slc20a1-/-placenta, confirming that Slc20a1 loss reduced trophoblast syncytiotrophoblast 1 (SynT-I) coverage. Next, we examined the cell type-specific Slc20a1 expression and SynT molecular pathways in silico and identified Notch/Wnt as a pathway of interest that regulates trophoblast differentiation. We further observed that specific trophoblast lineages express Notch/Wnt genes that associate with endothelial cell tip-and-stalk cell markers. In conclusion, our findings support that Slc20a1 mediates the symport of Pi into SynT cells, providing critical support for their differentiation and angiogenic mimicry function at the developing maternal-fetal interface.

Asymmetrical Transport of Thyroxine Across Human Term Placenta.

Background: Fetal development is crucially dependent on thyroid hormone (TH). Maternal-to-fetal transfer of TH is a prerequisite for fetal TH availability, particularly in the first half of pregnancy. The mechanisms of transplacental transport of TH, however, are yet poorly understood. We, therefore, investigated the TH transport processes across human placentas using an ex vivo perfusion system. Methods: Intact cotyledons from term placentas of uncomplicated pregnancies were cannulated within 30 minutes after delivery and the maternal and fetal circulations were re-established. One hundred nanomolar thyroxine (T4) was added to either the maternal or fetal circulation and perfusions run up to three hours during which samples were taken from both circulations at different time points. Variables included addition of iopanoic acid (IOP) to block activity of the deiodinase type 3 (D3) and bovine serum albumin (BSA) to trap released T4. T4 and 3,3',5'-triiodothyronine concentrations in the perfusates were measured by radioimmunoassays. Results: Maternal-to-fetal transfer was slow, with T4 barely detectable in the fetal circulation unless D3 was blocked by IOP. Fetal T4 was detected after three hours perfusion (10.6 ± 0.6 nM) when BSA (34 g/L) was added in the fetal circulation to trap the released T4. In contrast, fetal-to-maternal transfer of T4 was rapid and maternal T4 increased to 43.6 ± 5.5 nM. Conclusions: Maternal-to-fetal T4 transport is limited, whereas fetal-to-maternal transport is rapid indicating that T4 transport across human term placenta is an asymmetrical process. With the high D3 activity, our observations are compatible with a protective role of the placental barrier. Future studies should reveal how the placenta exerts its gatekeeper function in ensuring optimal TH passage to the fetus.

Antiproliferative and apoptotic effects of conditioned medium released from human amniotic epithelial stem cells on breast and cervical cancer cells.

Human amniotic membrane (hAM) and its cells have been proposed for several clinical applications, including cancer therapy. However, reports on the anticancer effects of human amniotic epithelial stem cells-conditioned media (hAECs-CM) are limited. This work aims to evaluate the anticancer effects of hAECs-CM on cervical cancer and breast cancer cell lines in vitro. Human term placentas were gained from uncomplicated Cesarean sections from healthy donor women. After amnion peeling from the chorion, its epithelial stem cells were isolated and cultured, and its conditioned medium (CM) was collected for experiments. MTT assay was performed to assess cancer cells viability. Migration rate of cancer cells was examined via wound healing assay. Cell-cycle distribution and apoptosis were determined using flow cytometry. Based on MTT assay hAECs-CM was cytotoxic against cancerous cell lines in a dose-time-dependent manner. After 48h of treatment with hAECs-CM pure, the cell viability of breast cancer cells includes MCF-7 and MDA-MB-231 reached to 73.2% and 65.5%, respectively. In the same situation, HeLa cervical cancer cell line revealed the lowest viability by 47.3%. The wound-healing assay displayed an incomplete wound closure of scratched MDA-MB-231 cells and significant inhibition of cell migration after hAECs-CM treatment. The results also revealed that hAECs-CM exerted anti-proliferation activity by prompting cell cycle arrest and apoptosis of cancer cells.Conclusions: hAECs-CM is a potent candidate for inducing apoptosis and simultaneously inhibition of the proliferation and migration of cancer cells via inhibiting cell cycle blockade.

Placental F4-Neuroprostanes and F2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity

We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.

Mice Placental ECM Components May Provide A Three-Dimensional Placental Microenvironment.

Bioethical limitations impair deeper studies in human placental physiology, then most studies use human term placentas or murine models. To overcome these challenges, new models have been proposed to mimetize the placental three-dimensional microenvironment. The placental extracellular matrix plays an essential role in several processes, being a part of the establishment of materno-fetal interaction. Regarding these aspects, this study aimed to investigate term mice placental ECM components, highlighting its collagenous and non-collagenous content, and proposing a potential three-dimensional model to mimetize the placental microenvironment. For that, 18.5-day-old mice placenta, both control and decellularized (n = 3 per group) were analyzed on Orbitrap Fusion Lumos spectrometer (ThermoScientific) and LFQ intensity generated on MaxQuant software. Proteomic analysis identified 2317 proteins. Using ECM and cell junction-related ontologies, 118 (5.1%) proteins were filtered. Control and decellularized conditions had no significant differential expression on 76 (64.4%) ECM and cell junction-related proteins. Enriched ontologies in the cellular component domain were related to cell junction, collagen and lipoprotein particles, biological process domain, cell adhesion, vasculature, proteolysis, ECM organization, and molecular function. Enriched pathways were clustered in cell adhesion and invasion, and labyrinthine vasculature regulation. These preserved ECM proteins are responsible for tissue stiffness and could support cell anchoring, modeling a three-dimensional structure that may allow placental microenvironment reconstruction.

Lower HLA-G levels in extravillous trophoblasts of human term placenta in gestational diabetes mellitus than in normal controls

The non-classical human leucocyte antigen (HLA) class I molecule HLA-G is widely known to play a major role in feto-maternal tolerance. We tested the hypothesis that HLA-G expression is altered in placentas of women with gestational diabetes mellitus (GDM) in a specific pattern that depends on fetal sex. HLA-G expression was analysed in a total of 80 placentas (40 placentas from women with GDM and 40 healthy controls) by immunohistochemistry using the semi-quantitative immunoreactive score (IRS). Double immunofluorescence staining identified the cells expressing HLA-G in the decidua and allowed evaluation of the expression pattern. We found a significant (p < 0.001) reduction of HLA-G expression in extravillous cytotrophoblasts (EVTs) in the placentas of women with GDM as compared to the healthy controls and were able to demonstrate that this downregulation was not due to a loss of cell number, but to a loss of expression intensity. A special change in the cell pattern of EVTs was observed, with these cells showing an obvious decrease in HLA-G expression on their cell surface. No significant differences according to fetal sex were found. These data show a possible association between decreased HLA-G expression and presence of GDM and provide new insights into altered placental function in women with GDM.

Perinatal Stem Cell Therapy to Treat Type 1 Diabetes Mellitus: A Never-Say-Die Story of Differentiation and Immunomodulation

Human term placenta and other postpartum-derived biological tissues are promising sources of perinatal cells with unique stem cell properties. Among the massive current research on stem cells, one medical focus on easily available stem cells is to exploit them in the design of immunotherapy protocols, in particular for the treatment of chronic non-curable human diseases. Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells and perinatal cells can be harnessed both to generate insulin-producing cells for beta cell replenishment and to regulate autoimmune mechanisms via immunomodulation capacity. In this study, the strong points of cells derived from amniotic epithelial cells and from umbilical cord matrix are outlined and their potential for supporting cell therapy development. From a basic research and expert stem cell point of view, the aim of this review is to summarize information regarding the regenerative medicine field, as well as describe the state of the art on possible cell therapy approaches for diabetes.

Assisted reproductive technology causes reduced expression of amino acid transporters in human full-term placentas.

In the mouse model, manipulations of assisted reproductive technology (ART) can lead to enlarged placentas and influence the expression of amino acid transporters in placentas during mid-to late-gestation. However, it is uncertain whether those abnormal changes presented in ART mouse placentas also occur in human ART placentas. We choose the placenta tissue of pregnant woman by ART in term birth (ART group) and by natural pregnancy in term birth (control group) to compare the birth weight of the baby, placental weight and ratio of the fetal/placental weight of these two groups. We then detect the mRNA and protein expression of placental amino acid transporter genes (SNAT1, SNAT2, SNAT4, LAT1 and LAT2) in these two groups by real-time quantitative PCR, Western blot and immunofluorescence staining. Additionally, the PI3K-AKT-mTOR signaling activity was also analyzed. There were no statistical differences in new birth weight between the ART group and the control group. Compared with the control group, the placenta weight of baby was significantly higher in ART group and ratio of the fetal/placental weight was significantly lower in ART group. We found that the mRNA and protein expression of A system of amino acid transporter SNAT1, SNAT2 and SNAT4 in placenta were significantly down-regulated in ART group compared with placentas from natural pregnancies. Additionally, there were no statistical differences of the mRNA and protein expression of L system of amino acid transporter LAT1 between these two groups, but amino acid transporter LAT2 in placenta was significantly down-regulated in ART group. Furthermore, the PI3K-AKT-mTOR signaling activity was inhibited in ART group. ART leads to the expressions of amino acid transporter genes SNAT1, SNAT2, SNAT4 and LAT2 significantly down-regulated in placenta accompanied by the PI3K-AKT-mTOR signaling inhibition, which suggests that ART may affect the function of placenta amino acid transporter during the late pregnancy, leading to enlarged placentas and probably low birth weight.

ODP434 Maternally-Derived Pancreatic Extracellular Vesicle Encompassed miRNAs Influence Placental Development in Pregnancies Complicated by Gestational Diabetes

Abstract Pregnancies affected by gestational diabetes (GDM) commonly result in large-for-gestational-age (LGA) infants; these infants have an increased risk of developing cardiometabolic complications compared to appropriate-for-gestational-age (AGA) infants. The mechanisms responsible are unclear but GDM/LGA is associated with altered placental development/function. We have recently reported altered levels of extracellular vesicle (EV) encapsulated miRNAs, including miR-375 (a pancreatic-specific miRNA) in maternal serum prior to the onset of LGA. We propose that the EVs containing miR-375 are produced by maternal pancreas, and that increased miR-375 in maternal circulation contributes to LGA by influencing placental development/function. Human placental tissue was collected from GDM pregnancies that delivered AGA (n=14) or LGA infants (n=10). Levels of mature miR-375 and primary transcript (pri-miR-375) were measured by QPCR. Mature miR-375 was increased in GDM-LGA (4.74-fold; p&amp;lt;0. 01) compared to GDM AGA placentae. Mature miR-375, but not pri-miR-375, was detected in human placenta suggesting that miR-375 is not produced in the placenta but instead is transported, potentially via EVs in maternal circulation. Intact human pancreatic islets (20,000 IEQ/patient) were obtained through the Integrated Islet Distribution Program (IIDP) from female donors of reproductive age. Islets were cultured in EV-depleted media containing 5.5mM (normoglycemia) or 7mM (mild hyperglycaemia) glucose for 3 days. Islet purity and viability were confirmed using dithizone incorporation and trypan blue exclusion, respectively. Media was collected at 24-hour intervals, pooled from all time points, concentrated and EVs were isolated by size exclusion chromatography. Confirmation of the presence of EVs was confirmed by electron microscopy (typical cup-shape morphology of EVs), nanoparticle tracking analysis (NTA; mean size of 83.5-163.2nm; concentration of 1.28×109-1.82×1010 particles/ml), Western blotting (EV-enriched proteins). QPCR confirmed that mature miR-375 was present in islet-derived EVs and revealed that levels were altered following culture in 7mM glucose compared to 5.5mM. Islet-derived EVs were labelled with maleimide-488 and uptake into explants of normal human term placenta was confirmed using fluorescent microscopy=3). miR-375 was overexpressed in normal human placental explants (by 30-fold, p&amp;lt;0. 05; n=6) using specific mimics (100nM for 72 hours) and TMT mass spectrometry was performed to assess the impact of miR-375 overexpression on the placental proteome. Functional enrichment analysis (FEA) was performed on differentially expressed proteins (DEP; P&amp;lt;0. 05; -0.41≥log2foldchange≥0.58) using over representation analysis and Ingenuity Pathway Analysis. This revealed that DEGs were significantly enriched in pathways associated with placental growth, mitochondrial function and glucose metabolism. Our data demonstrates that miR-375 is increased in the placenta in GDM/LGA and that this influences placental development/function. miR-375 does not appear to be produced in the placenta but instead, is likely released in EVs from maternal pancreas under conditions of hyperglycaemia and transported to the placenta, via maternal circulation. This provides insight into the potential mechanisms contributing to LGA in pregnancies complicated by GDM. Presentation: No date and time listed

Global microRNA and protein expression in human term placenta.

Description of the global expression of microRNAs (miRNAs) and proteins in healthy human term placentas may increase our knowledge of molecular biological pathways that are important for normal fetal growth and development in term pregnancy. The aim of this study was to explore the global expression of miRNAs and proteins, and to point out functions of importance in healthy term placentas. Placental samples (n = 19) were identified in a local biobank. All samples were from uncomplicated term pregnancies with vaginal births and healthy, normal weight newborns. Next-generation sequencing and nano-scale liquid chromatographic tandem mass spectrometry were used to analyse miRNA and protein expression, respectively. A total of 895 mature miRNAs and 6,523 proteins were detected in the placentas, of which 123 miRNAs and 346 proteins were highly abundant. The miRNAs were in high degree mapped to chromosomes 19, 14, and X. Analysis of the highly abundant miRNAs and proteins showed several significantly predicted functions in common, including immune and inflammatory response, lipid metabolism and development of the nervous system. The predicted function inflammatory response may reflect normal vaginal delivery, while lipid metabolism and neurodevelopment may be important processes for the term fetus. The data presented in this study, with complete miRNA and protein findings, will enhance the knowledge base for future research in the field of placental function and pathology.

Deeply in Plasticenta: Presence of Microplastics in the Intracellular Compartment of Human Placentas.

Highlights What are the main findings? For the first time, microplastics were detected and localized by electron microscopy in human placentas.The presence of microplastics was correlated with ultrastructural alterations of some cell organelles in placental tissue, mainly in the syncytiotrophoblast. What is the implication of the main finding? Microplastics in human placentas could contribute to the activation of pathological traits, such as oxidat ive stress, apoptosis, and inflammation.Microplastics in human placentas may cause long-term effects on human health. Microplastics (MPs) are defined as plastic particles smaller than 5 mm. They have been found almost everywhere they have been searched for and recent discoveries have also demonstrated their presence in human placenta, blood, meconium, and breastmilk, but their location and toxicity to humans have not been reported to date. The aim of this study was twofold: 1. To locate MPs within the intra/extracellular compartment in human placenta. 2. To understand whether their presence and location are associated with possible structural changes of cell organelles. Using variable pressure scanning electron microscopy and transmission electron microscopy, MPs have been localized in ten human placentas. In this study, we demonstrated for the first time the presence and localization in the cellular compartment of fragments compatible with MPs in the human placenta and we hypothesized a possible correlation between their presence and important ultrastructural alterations of some intracytoplasmic organelles (mitochondria and endoplasmic reticulum). These alterations have never been reported in normal healthy term pregnancies until today. They could be the result of a prolonged attempt to remove and destroy the plastic particles inside the placental tissue. The presence of virtually indestructible particles in term human placenta could contribute to the activation of pathological traits, such as oxidative stress, apoptosis, and inflammation, characteristic of metabolic disorders underlying obesity, diabetes, and metabolic syndrome and partially accounting for the recent epidemic of non-communicable diseases.

Quantification of androgens and their precursors in full-term human placenta

Quantification of androgens and their precursors in full-term human placenta

Morphological variations in Placentas among Deliveries in the Department of Obstetrics and Gynaecology in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

The full term human placenta is a flattened discoidal mass with an approximately circular or oval outline. However, variations can be present in the morphology in the form of bidiscoidal shape, lobed, diffused, fenestrated or circumvallate. The objective of the study was to find out the prevalence of morphological variations in placentas among deliveries in the Department of Obstetrics and Gynaecology in a tertiary care centre. A descriptive cross-sectional study was conducted among total in the Department of Obstetrics and Gynaecology in a tertiary care centre after receiving ethical approval from the Institutional Review Committee (Reference number: 2308202105). The study was conducted between September 2021 to November 2021 and the shape of the placenta was observed and the variations present were noted. Point estimate and 95% Confidence Interval were calculated. Out of 105 placentas observed, morphological variations were seen in two (1.91%) (0-4.53, 95% Confidence Interval). One (50%) was observed to be placenta succenturiata and one (50%) was triangular in shape. The prevalence of morphological variations in placentas was found to be higher than the studies done in similar settings.

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy.

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.

Functional reorganization of monoamine transport systems during villous trophoblast differentiation: evidence of distinct differences between primary human trophoblasts and BeWo cells

BackgroundThree primary monoamines—serotonin, norepinephrine, and dopamine—play major roles in the placenta-fetal brain axis. Analogously to the brain, the placenta has transport mechanisms that actively take up these monoamines into trophoblast cells. These transporters are known to play important roles in the differentiated syncytiotrophoblast layer, but their status and activities in the undifferentiated, progenitor cytotrophoblast cells are not well understood. Thus, we have explored the cellular handling and regulation of monoamine transporters during the phenotypic transitioning of cytotrophoblasts along the villous pathway.MethodsExperiments were conducted with two cellular models of syncytium development: primary trophoblast cells isolated from the human term placenta (PHT), and the choriocarcinoma-derived BeWo cell line. The gene and protein expression of membrane transporters for serotonin (SERT), norepinephrine (NET), dopamine (DAT), and organic cation transporter 3 (OCT3) was determined by quantitative PCR and Western blot analysis, respectively. Subsequently, the effect of trophoblast differentiation on transporter activity was analyzed by monoamine uptake into cells.ResultsWe present multiple lines of evidence of changes in the transcriptional and functional regulation of monoamine transporters associated with trophoblast differentiation. These include enhancement of SERT and DAT gene and protein expression in BeWo cells. On the other hand, in PHT cells we report negative modulation of SERT, NET, and OCT3 protein expression. We show that OCT3 is the dominant monoamine transporter in PHT cells, and its main functional impact is on serotonin uptake, while passive transport strongly contributes to norepinephrine and dopamine uptake. Further, we show that a wide range of selective serotonin reuptake inhibitors affect serotonin cellular accumulation, at pharmacologically relevant drug concentrations, via their action on both OCT3 and SERT. Finally, we demonstrate that BeWo cells do not well reflect the molecular mechanisms and properties of healthy human trophoblast cells.ConclusionsCollectively, our findings provide insights into the regulation of monoamine transport during trophoblast differentiation and present important considerations regarding appropriate in vitro models for studying monoamine regulation in the placenta.