Search Results (74)

Placenta and visceral adipose tissue (VAT) are implicated in the development of gestational diabetes mellitus (GDM). In the present study, we examined the whole-transcriptomic profile of both tissues in GDM women to elucidate the molecular basis of GDM pathogenesis. The whole-transcriptome profile was analyzed in placenta and VAT from at-term patients with GDM and controls using RNA-seq. qPCR was used to validate several differentially expressed genes (DEGs). A total of 179 DEGs were observed in the placenta and 4 in VAT, including both up- and downregulated genes. The expression of the selected mRNAs for validation was consistent with the sequencing results. An analysis of the placental upregulated DEGs in the GDM women showed enrichment in functions including the G-protein-coupled receptor signaling pathway, organophosphate biosynthetic process, and phospholipid metabolic process, while the downregulated DEGs were enriched in cell motility and the cell migration process. The target pathways of DEGs in VAT are related to cancer and to the activation of the complement cascade. Molecular pathways involved in G-protein-coupled receptor signaling, the organophosphate biosynthetic process, the phospholipid metabolic process, and cell motility and cell migration are altered in the placentas of GDM women. Moreover, a disordered complement cascade might take place in the VAT of GDM women. Full article

Placental dysfunction underlies the major obstetric syndromes, including preeclampsia, fetal growth restriction, placenta accreta spectrum, pregnancy loss, and monochorionic twin complications. Recent molecular studies have revealed that dysregulated oxygen sensing, impaired angiogenic signaling, altered immune tolerance, and defective trophoblast fusion represent shared pathogenic pathways that converge across these disorders. Integrating morphological evidence with mechanistic data highlights how villous maldevelopment, shallow trophoblast invasion, and aberrant vascular remodeling translate into clinical disease. Advances in biomarker research have already transformed clinical care: the sFlt-1/PlGF ratio is now established in the prediction and management of preeclampsia, while placental proteins such as PAPP-A and PP13, nucleic acid signatures including cfDNA, cfRNA and miRNAs, and extracellular vesicle cargo show promising potential for early, non-invasive detection of placental pathology. Multi-omics approaches, particularly single-cell and spatial transcriptomics combined with proteomic and metabolomic profiling, are paving the way for composite diagnostic panels that capture the polygenic and multicellular nature of placental disease. This review synthesizes current knowledge of molecular mechanisms, histological correlates, and translational biomarkers, and outlines how precision obstetrics may emerge from bridging mechanistic discoveries with clinical applications. Full article

AT-hook motif nuclear-localized (AHL) genes play critical roles in chromatin remodeling and gene transcription regulation, profoundly influencing plant growth, development, and stress responses. While AHL genes have been extensively characterized in multiple plant species, their biological functions in pepper (Capsicum annuum L.) remain largely uncharacterized. In this study, we identified 45 CaAHL genes in the pepper genome through bioinformatics approaches. Comprehensive analyses were conducted to examine their chromosomal distribution, phylogenetic relationships, and the structural and functional features of their encoded proteins. Phylogenetic clustering classified the CaAHL proteins into six distinct subgroups. Transcriptome profiling revealed widespread expression of CaAHL genes across diverse tissues—including roots, stems, leaves, flowers, seeds, pericarp, placenta, and fruits—at various developmental stages. Quantitative real-time PCR further demonstrated that CaAHL1, CaAHL33, and CaAHL23 exhibited consistently high expression throughout flower bud development, whereas CaAHL36 showed preferential upregulation at early bud development stages. Expression profiling under hormone treatments and abiotic stresses indicated that CaAHL36 and CaAHL23 are auxin-inducible but are repressed by ABA, cold, heat, salt, and drought stress. Subcellular localization assays in Nicotiana benthamiana leaf epidermal cells showed that both CaAHL36 and CaAHL23 were predominantly localized in the nucleus, with faint expression also detected in the cytoplasm. Collectively, this study provides foundational insights into the CaAHL gene family, laying the groundwork for future functional investigations of these genes in pepper. Full article

The prevalence, pathogenesis, and long-term consequences of hypertension differ significantly across the sexes, and pregnancy is a special physiological stress test that can reveal a woman’s underlying cardiovascular sensitivity. In addition to being direct risks to the health of the mother and fetus, hypertensive disorders of pregnancy (HDPs), especially preeclampsia, are also reliable indicators of future hypertension and cardiovascular disease in those who are afflicted. Fetal sex has a substantial impact on maternal vascular adaptation, according to new data from placental transcriptomics and epigenetics. This may be due to variations in the expression of angiogenic, immunomodulatory, and vasoactive genes. Sex-specific patterns of placental function, inflammation, and endothelium control are specifically influenced by X-linked gene dosage, escape from X-inactivation, and sex chromosomal composition. These biological variations highlight the placenta’s potential function as a mediator and indicator of maternal cardiovascular risk, and they may help to explain why the incidence and severity of hypertensive pregnancy challenges vary depending on the fetal sex. The purpose of this review is to summarize the state of the art regarding how placental genetics and fetal sex influence maternal hypertensive risk both during and after pregnancy. Additionally, it will investigate how these findings may influence sex-specific cardiovascular screening, prediction, and prevention methods. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of AS in PE remain poorly understood. Methods: To elucidate AS-mediated regulatory pathways in PE, a total of 38 fresh-frozen placental samples, including 13 pre-eclampsia samples and 25 normal control samples, were collected from Renmin Hospital of Wuhan University between 1 February and 30 July 2022. We performed transcriptome sequencing of seven PE and seven normal placentas to identify differentially spliced events. After quality control and adapter trimming, raw sequencing reads were aligned to the human reference genome using STAR. Differential exon usage was analyzed using DEXSeq (version 1.36.0), and exons with an adjusted p-value < 0.05 and a fold change greater than 2 or less than 0.5 were considered significantly differentially spliced. Functional assays, including CCK8, colony formation, and cell cycle analyses, were conducted to assess trophoblast proliferation, whereas wound healing and Transwell assays were used to evaluate trophoblast migration and invasion using the HTR-8/SVneo cell line. RNA immunoprecipitation sequencing (RIP-seq) and RNA stability assays were employed to investigate mRNA interactions and stability. Results: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) emerged as a key RNA-binding protein associated with alternative splicing regulation, intersecting both AS-related candidate genes and known splicing factors, although it is not a classical splicing factor itself. IGF2BP3 overexpression markedly enhanced HTR-8/SVneo trophoblast proliferation, migration, and invasion while suppressing ROS activation. RNA-seq, RIP-seq, and RNA stability assays revealed that IGF2BP3 directly interacts with and enhances the stability of PDE3A mRNA. Functional rescue experiments confirmed that PDE3A knockdown partially abrogated IGF2BP3-mediated trophoblast progression. Furthermore, miR-196a-5p was identified as a negative regulator of IGF2BP3 via miRNA inhibitor/mimic transfection, qRT-PCR, and functional assays, confirming that miR-196a-5p overexpression downregulates IGF2BP3, thereby impairing trophoblast migration and proliferation. Notably, restoring IGF2BP3 expression reversed these inhibitory effects. Conclusions: Our findings reveal a previously unrecognized regulatory axis in PE in which miR-196a-5p suppresses IGF2BP3 expression, leading to PDE3A mRNA destabilization and impaired trophoblast function. This study offers mechanistic insights into PE pathogenesis and identifies IGF2BP3 as a potential therapeutic target. Full article

This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment group (P). Groups T and P received oral administration of CPP (2000 mg/kg/day) and vitamin C (100 mg/kg/day), respectively, while groups M, T, and P were subjected to intraperitoneal injections of D-galactose (D-gal) (300 mg/kg/day). Group N received an equivalent volume of normal saline via intraperitoneal injection. Treatments were administered once daily for 8 weeks. The results demonstrated that CPP significantly alleviated D-galactose-induced intestinal structural damage, increasing the villus height-to-crypt depth ratio and reducing serum diamine oxidase (DAO) and lipopolysaccharide (LPS) levels. CPP notably alleviated intestinal oxidative stress and inflammation, restored tight junction expression, and enhanced intestinal barrier integrity. Transcriptome sequencing identified 1396 DEGs associated with CPP’s effects, highlighting TLR4, IL-1β, and Mmp9 as core regulatory genes through protein–protein interaction network analysis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses implicated the TLR4/NF-κB signaling pathway, which was further validated. Western blotting confirmed that CPP significantly down-regulated TLR4, IKKβ, and p-NF-κB p65 protein expression in the intestines of aging mice. In conclusion, CPP effectively alleviates D-gal-induced intestinal barrier damage in aging mice by enhancing antioxidant defense and inhibiting the TLR4/NF-κB signaling pathway, thereby diminishing inflammation and protecting intestinal barrier integrity. Full article

Demographic studies have revealed a strong association between exposure to high ambient temperatures during pregnancy and increased risks of preterm birth (PTB). The mechanism underlying this association is unclear, but it is plausible that altered placental function may contribute to it. In this study, we conducted differential gene expression analysis, gene set enrichment analysis (GSEA), and gene ontology (GO) analysis on bulk RNA-seq data from human placentas delivered at term and preterm during the warmer months compared to placentas delivered at term and preterm during the colder months in the UK. We detected 48 differentially expressed genes in preterm placentas delivered during the warmer months compared to preterm placentas delivered during the colder months, the majority of which were inflammatory cytokines and chemokines, including SERPINA1, IL1B, CCL3, CCL3L3, CCL4, CCL4L2, CCL20, and CXCL8. The GSEA positively enriched 17 signalling pathways, including the NF-κB, IL17, Toll-like receptor, and chemokine signalling pathways in preterm placentas delivered during warmer months. These results were not observed in the placentas delivered at term during the same times of the year. The GO analysis revealed several enhanced biological processes, including neutrophil, granulocyte, monocyte, and lymphocyte chemotaxis, as well as inflammatory and humoral immune responses in preterm placentas, but not in placentas delivered at term in the summer. We conclude that maternal exposure to warm environmental temperatures during pregnancy likely alters the placental transcriptomes towards inflammation and immune regulation, potentially leading to PTB. Full article

Background/Objectives: The success or failure of embryo fixation is crucial for embryo attachment and later development. As an epithelial chorioallantoic placenta-type animal, the horse has a special process of embryo implantation, and the mechanism of embryo fixation in horses is still unclear. Methods: In this study, the structural and transcriptomic characteristics of endometrial tissue from the fixed and nonfixed sides of 20-day gestation embryos in Mongolian horses were investigated to search for important genes and potential molecular markers associated with the fixation phase of equine embryos. Results: A comparison of the structures of the endometrial tissues of the two sides revealed that the endometrium on the fixed side presented distinctive features, which were characterized mainly by the development of glands on the fixed side compared with those on the nonfixed side. A total of 3987 differentially expressed genes were identified in the transcriptome, among which 1931 genes were highly expressed on the fixed side of the embryo, including CDH1, DRA, DQB, CLND2, BOLA-DQB, CLDN10, PTGER2, and PTGFR. The differentially expressed genes were enriched in biological processes such as cell adhesion, morphogenesis, NOD signaling, and vitamin uptake, as well as prostatic hormones. Conclusions: These results suggest that equine embryo fixation may depend at least on the regulation of prostaglandins and the establishment of cellular connections. This provides a foundation for exploring the molecular mechanisms of key genes and pathways related to equine embryo fixation and offers new insights into feeding management and the monitoring of mares in the early stages of pregnancy. Full article

Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth. Using a direct reprogramming approach previously described for dermal fibroblasts, we investigated the effects of three supplements (A-485, BMP4, and EPZ-6438) to assess their potential to enhance iTSC induction. The generated iTSCs fulfilled the criteria for bona fide first-trimester trophoblasts and exhibited key functional capacities, including long-term self-renewal, differentiation into hormone-producing syncytiotrophoblasts and invasive extravillous trophoblasts, and the formation of organoids. Furthermore, transcriptomic analysis revealed high similarity between the generated iTSCs and trophoblast stem cells derived from first-trimester placental tissue. The supplements did not improve the generation of iTSCs. In conclusion, we successfully generated bona fide iTSCs from term umbilical cord using a direct reprogramming approach, providing a robust and clinically relevant model to study early placentation mechanisms in patient-derived trophoblasts. Full article

The placenta is a vital organ in bovine reproduction, crucial for blood supply, nutrient transport, and embryonic development. It plays an essential role in the intrauterine growth of calves. However, the molecular mechanisms governing placental function in calves remain inadequately understood. Methods: We established transcriptome and proteome databases for low-birth-weight (LB) and high-birth-weight (HB) calf placentae, identifying key genes and proteins associated with birth weight through bioinformatics analyses that included functional enrichment and protein–protein interactions (PPIs). Both mRNA and protein levels were validated. Results: A total of 1494 differentially expressed genes (DEGs) and 294 differentially expressed proteins (DEPs) were identified when comparing the LB group to the HB group. Furthermore, we identified 53 genes and proteins exhibiting significant co-expression across both transcriptomic and proteomic datasets; among these, 40 were co-upregulated, 8 co-downregulated, while 5 displayed upregulation at the protein level despite downregulation at the mRNA level. Functional enrichment analyses (GO and KEGG) and protein–protein interaction (PPI) analysis indicate that, at the transcriptional level, the primary factor contributing to differences in calf birth weight is that the placenta of the high-birth-weight (HB) group provides more nutrients to the fetus, characterized by enhanced nutrient transport (SLC2A1 and SLC2A11), energy metabolism (ACSL1, MICALL2, PAG2, COL14A1, and ELOVL5), and lipid synthesis (ELOVL5 and ELOVL7). In contrast, the placenta of the low-birth-weight (LB) group prioritizes cell proliferation (PAK1 and ITGA3) and angiogenesis. At the protein level, while the placentae from the HB group exhibit efficient energy production and lipid synthesis, they also demonstrate reduced immunity to various diseases such as systemic lupus erythematosus and bacterial dysentery. Conversely, the LB group placentae excel in regulating critical biological processes, including cell migration, proliferation, differentiation, apoptosis, and signal transduction; they also display higher disease immunity markers (COL6A1, TNC CD36, CD81, Igh-1a, and IGHG) compared to those of the HB group placentae. Co-expression analysis further suggests that increases in calf birth weight can be attributed to both high-efficiency energy production and lipid synthesis within the HB group placentae (ELOVL5, ELOVL7, and ACSL1), alongside cholesterol biosynthesis and metabolic pathways involving CYP11A1 and CYP17A1. Conclusion: We propose that ELOVL5, ELOVL7, ACSL1, CYP11A1, and CYP17A1 serve as potential protein biomarkers for regulating calf birth weight through the modulation of the fatty acid metabolism, lipid synthesis, and cholesterol levels. Full article

The epigenetic phenomenon of genomic imprinting is puzzling. While epigenetic modifications in general are widely known in most species, genomic imprinting in the animal kingdom is restricted to autosomes of therian mammals, mainly eutherians, and to a lesser extent in marsupials. Imprinting causes monoallelic gene expression. It represents functional haploidy of certain alleles while bearing the evolutionary cost of diploidization, which is the need of a complex cellular architecture and the danger of producing aneuploid cells by mitotic and meiotic errors. The parent-of-origin gene expression has stressed many theories. Most prominent theories, such as the kinship (parental conflict) hypothesis for maternally versus paternally derived alleles, explain only partial aspects of imprinting. The implementation of single-cell transcriptome analyses and epigenetic research allowed detailed study of monoallelic expression in a spatial and temporal manner and demonstrated a broader but much more complex and differentiated picture of imprinting. In this review, we summarize all these aspects but argue that imprinting is a functional haploidy that not only allows a better gene dosage control of critical genes but also increased cellular diversity and plasticity. Furthermore, we propose that only the occurrence of allele-specific gene regulation mechanisms allows the appearance of evolutionary novelties such as the placenta and the evolutionary expansion of the eutherian brain. Full article

A major factor limiting the development of somatic cell nuclear transfer (SCNT) technology is the low success rate of pregnancy, mainly due to placental abnormalities disrupting the maternal-fetal balance during pregnancy. Although there has been some progress in research on the abnormal enlargement of cloned bovine placenta, there are still few reports on the direct regulatory mechanisms of enlarged cloned bovine placenta tissue. In this study, we conducted sequencing and analysis of transcriptomics, proteomics, and metabolomics of placental tissues from SCNT cattle (n = 3) and control (CON) cattle (n = 3). The omics analysis results indicate abnormalities in biological functions such as protein digestion and absorption, glycolysis/gluconeogenesis, the regulation of lipid breakdown, as well as glycerolipid metabolism, and arginine and proline metabolism in the placenta of SCNT cattle. Integrating these analyses highlights critical metabolic pathways affecting SCNT cattle placenta, including choline metabolism and unsaturated fatty acid biosynthesis. These findings suggest that aberrant expressions of genes, proteins, and metabolites in SCNT placentas affect key pathways in protein digestion, growth hormone function, and energy metabolism. Our results suggest that abnormal protein synthesis, growth hormone function, and energy metabolism in SCNT bovine placental tissues contribute to placental hypertrophy. These findings offer valuable insights for further investigation into the mechanisms underlying SCNT bovine placental abnormalities. Full article

Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality worldwide, with the placenta playing a central role in disease pathophysiology. This review synthesizes recent advancements in understanding the molecular mechanisms underlying PE, focusing on placental genes, proteins, and genetic variants identified through multi-omic approaches. Transcriptomic studies in bulk placental tissue have identified many dysregulated genes in the PE placenta, including the PE signature gene, Fms-like tyrosine kinase 1 (FLT1). Emerging single-cell level transcriptomic data have revealed key cell types and molecular signatures implicated in placental dysfunction and PE. However, the considerable variability among studies underscores the need for standardized methodologies and larger sample sizes to enhance the reproducibility of results. Proteomic profiling of PE placentas has identified numerous PE-associated proteins, offering insights into potential biomarkers and pathways implicated in PE pathogenesis. Despite significant progress, challenges such as inconsistencies in study findings and lack of validation persist. Recent fetal genome-wide association studies have identified multiple genetic loci associated with PE, with ongoing efforts to elucidate their impact on placental gene expression and function. Future directions include the integration of multi-omic data, validation of findings in diverse PE populations and clinical subtypes, and the development of analytical approaches and experimental models to study the complex interplay of placental and maternal factors in PE etiology. These insights hold promise for improving risk prediction, diagnosis, and management of PE, ultimately reducing its burden on maternal and neonatal health. Full article

It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there is still limited information on the specific impact of maternal SARS-CoV-2 infection on vertical transmission. The current study focuses on a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother–newborn pairs affected by COVID-19 and those from unaffected controls. Additionally, it investigates the in situ expression of molecules involved in placental inflammation. The Papa Giovanni XXIII Hospital in Bergamo, Italy, has recorded three instances of intrauterine transmission of SARS-CoV-2. The first two cases occurred early in the pandemic and involved pregnant women in their third trimester who were diagnosed with SARS-CoV-2. The third case involved an asymptomatic woman in her second trimester with a twin pregnancy, who unfortunately delivered two stillborn fetuses due to the premature rupture of membranes. Transcriptomic analysis revealed significant differences in gene expression between the placentae of COVID-19-affected mother/newborn pairs and two matched controls. The infected and control placentae were matched for gestational age. According to the Benjamani–Hochberg method, 305 genes met the criterion of an adjusted p-value of less than 0.05, and 219 genes met the criterion of less than 0.01. Up-regulated genes involved in cell signaling (e.g., CCL20, C3, MARCO) and immune response (e.g., LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest their potential role in the inflammatory response to SARS-CoV-2. RNAscope^® technology, coupled with image analysis, was utilized to quantify the surface area covered by SARS-CoV-2, ACE2, IL-1β, IL-6, IL-8, IL-10, and TNF-α on both the maternal and fetal sides of the placenta. A non-statistically significant gradient for SARS-CoV-2 was observed, with a higher surface coverage on the fetal side (2.42 ± 3.71%) compared to the maternal side (0.74 ± 1.19%) of the placenta. Although not statistically significant, the surface area covered by ACE2 mRNA was higher on the maternal side (0.02 ± 0.04%) compared to the fetal side (0.01 ± 0.01%) of the placenta. IL-6 and IL-8 were more prevalent on the fetal side (0.03 ± 0.04% and 0.06 ± 0.08%, respectively) compared to the maternal side (0.02 ± 0.01% and 0.02 ± 0.02%, respectively). The mean surface areas of IL-1β and IL-10 were found to be equal on both the fetal (0.04 ± 0.04% and 0.01 ± 0.01%, respectively) and maternal sides of the placenta (0.04 ± 0.05% and 0.01 ± 0.01%, respectively). The mean surface area of TNF-α was found to be equal on both the fetal and maternal sides of the placenta (0.02 ± 0.02% and 0.02 ± 0.02%, respectively). On the maternal side, ACE-2 and all examined interleukins, but not TNF-α, exhibited an inverse mRNA amount compared to SARS-CoV-2. On the fetal side, ACE-2, IL-6 and IL-8 were inversely correlated with SARS-CoV-2 (r = −0.3, r = −0.1 and r = −0.4, respectively), while IL-1β and IL-10 showed positive correlations (r = 0.9, p = 0.005 and r = 0.5, respectively). TNF-α exhibited a positive correlation with SARS-CoV-2 on both maternal (r = 0.4) and fetal sides (r = 0.9) of the placenta. Further research is needed to evaluate the correlation between cell signaling and immune response genes in the placenta and the vertical transmission of SARS-CoV-2. Nonetheless, the current study extends our comprehension of the molecular and immunological factors involved in SARS-CoV-2 placental infection underlying maternal–fetal transmission. Full article

Birth weight is a complex multifactorial trait relevant to health states and disease risks in later life. The placenta is essential for proper fetal growth and facilitates gas, nutrient, and waste exchange between the mother and developing fetus. How changes in placental DNA methylation affect fetal birth weight remains to be fully elucidated. In this study, we used whole-genome bisulfite sequencing and RNA sequencing to reveal a global map of DNA methylation and gene expression changes between the placentas of highest birth weight and lowest birth weight piglets in the same litters. The transcriptome analysis identified 1682 differential expressed genes and revealed key transcriptional properties in distinct placentas. We also identified key transcription factors that may drive the differences in DNA methylome patterns between placentas. The decrease in DNA methylation level in the promoter was associated with the transcriptional activation of genes associated with angiogenesis, extracellular matrix remodeling, and transmembrane transport. Our results revealed the regulatory role of DNA methylation in gene transcription activity leading to the differences in placental morphological structures and birth weights of piglets. These results could provide novel clues to clarify the underlying regulatory mechanisms of placental development and fetal growth. Full article