-
International Journal of Molecular... Nov 2023Transforming growth factor beta (TGF-β), a multifunctional cytokine, is one of the most important inflammatory cytokines closely related to pregnancy. It plays... (Review)
Review
Transforming growth factor beta (TGF-β), a multifunctional cytokine, is one of the most important inflammatory cytokines closely related to pregnancy. It plays significant roles in hormone secretion, placental development, and embryonic growth during pregnancy. TGF-β is implicated in embryo implantation and inhibits the invasion of extraepithelial trophoblast cells. It also moderates the mother-fetus interaction by adjusting the secretion pattern of immunomodulatory factors in the placenta, consequently influencing the mother's immune cells. The TGF-β family regulates the development of the nervous, respiratory, and cardiovascular systems by regulating gene expression. Furthermore, TGF-β has been associated with various pregnancy complications. An increase in TGF-β levels can induce the occurrences of pre-eclampsia and gestational diabetes mellitus, while a decrease can lead to recurrent miscarriage due to the interference of the immune tolerance environment. This review focuses on the role of TGF-β in embryo implantation and development, providing new insights for the clinical prevention and treatment of pregnancy complications.
Topics: Pregnancy; Female; Humans; Placenta; Transforming Growth Factor beta; Trophoblasts; Placentation; Cytokines; Pre-Eclampsia
PubMed: 38069201
DOI: 10.3390/ijms242316882 -
Development (Cambridge, England) Aug 2023The invasive trophoblast cell lineages in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These...
The invasive trophoblast cell lineages in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These observations have led to the rat becoming an especially useful animal model for studying hemochorial placentation. However, our understanding of similarities or differences between regulatory mechanisms governing rat and human invasive trophoblast cell populations is limited. In this study, we generated single-nucleus ATAC-seq data from gestation day 15.5 and 19.5 rat uterine-placental interface tissues, and integrated the data with single-cell RNA-seq data generated at the same stages. We determined the chromatin accessibility profiles of invasive trophoblast, natural killer, macrophage, endothelial and smooth muscle cells, and compared invasive trophoblast chromatin accessibility with extravillous trophoblast cell accessibility. In comparing chromatin accessibility profiles between species, we found similarities in patterns of gene regulation and groups of motifs enriched in accessible regions. Finally, we identified a conserved gene regulatory network in invasive trophoblast cells. Our data, findings and analysis will facilitate future studies investigating regulatory mechanisms essential for the invasive trophoblast cell lineage.
Topics: Animals; Pregnancy; Rats; Cell Nucleus; Chromatin; Gene Regulatory Networks; Placenta; Single-Cell Gene Expression Analysis; Transcription Factors; Trophoblasts; Uterus; Female
PubMed: 37417811
DOI: 10.1242/dev.201826 -
Human Reproduction Update Jan 2024The establishment of maternal-fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide... (Review)
Review
BACKGROUND
The establishment of maternal-fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal-fetal interface and their associations with pathological processes.
OBJECTIVE AND RATIONALE
This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal-fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal-fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed.
SEARCH METHODS
A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal-fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included.
OUTCOMES
The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal-fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal-fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal-fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groundwork for further exploration of glycans in reproductive biology under both physiological and pathological conditions.
WIDER IMPLICATIONS
A deep understanding of the functions of glycan structures would provide insights into the molecular mechanisms underlying their involvement in the physiological and pathological regulation of early pregnancy. Glycans may also potentially serve as novel early predictive markers and therapeutic targets for repeated implantation failure, pregnancy loss, and other pregnancy complications.
Topics: Pregnancy; Female; Humans; Glycosylation; Abortion, Spontaneous; Placenta; Trophoblasts; Glycosyltransferases; Polysaccharides
PubMed: 37699855
DOI: 10.1093/humupd/dmad024 -
Placenta Dec 2023Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that...
INTRODUCTION
Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that could impact on placental function and could mediate the adverse outcomes. The purpose of this study was to compare the major placental histological characteristics of non-diabetic obese women to lean controls, focusing on uncomplicated pregnancies.
METHODS
Prospective case-control study comparing placental histopathological features between 122 non-diabetic obese women and 185 non-obese controls. The analysis was performed on overall subjects, then uncomplicated pregnancies from both groups were analyzed. Placenta pathologic findings were recorded according to standard classification.
RESULTS
Both in overall analysis and among the subset of subjects with an uncomplicated pregnancy, obese subjects had higher risks of maternal vascular malperfusion (MVM) (respectively OR=2.2, 95%CI =1.3-3.7 and OR=4.2, 95%CI=2.1-8.5), fetal vascular malperfusion (FVM) (respectively OR=6.3, 95%CI=3.1-12.5 and OR=7.2, 95%CI=3-17.2), maternal and fetal inflammatory response placental lesions and villitis (VUE) (respectively OR=2.5, 95%CI=1.1-5.6 and OR=10.8, 95%CI=3.3-35.3) compared to controls. Among uncomplicated pregnancies and after adjustment for confounders, first trimester BMI was significantly associated with overall MVM, overall FVM, maternal inflammatory, fetal inflammatory response and VUE.
DISCUSSION
Placentas from obese women showed a significantly higher risk of maternal and fetal vascular and inflammatory placental lesions, both in overall population and in the subgroup with uncomplicated pregnancies. The metabolic and inflammatory dysfunctions typical of obesity could have an impact on placental development and function, which could be a mediator of the detrimental effects of obesity on pregnancy outcome and on future health of the offspring.
Topics: Pregnancy; Female; Humans; Placenta; Case-Control Studies; Pregnancy Outcome; Placenta Diseases; Obesity
PubMed: 37922644
DOI: 10.1016/j.placenta.2023.10.011 -
Frontiers in Immunology 2024The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide... (Review)
Review
The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide nutrients, gases, and hormones to the developing fetus. The placenta has endocrine functions, orchestrates maternal adaptations to pregnancy at different periods of pregnancy, and acts as a selective barrier to minimize exposure of developing fetus to xenobiotics, pathogens, and parasites. Despite the fact that this ancient organ is central for establishment of a normal pregnancy in eutherians, the placenta remains one of the least studied organs. The first step of pregnancy, embryo implantation, is finely regulated by the trophoectoderm, the precursor of all trophoblast cells. There is a bidirectional communication between placenta and endometrium leading to decidualization, a critical step for maintenance of pregnancy. There are three-direction interactions between the placenta, maternal immune cells, and the endometrium for adaptation of endometrial immune system to the allogeneic fetus. While 65% of all systemically expressed human proteins have been found in the placenta tissues, it expresses numerous placenta-specific proteins, whose expression are dramatically changed in gestational diseases and could serve as biomarkers for early detection of gestational diseases. Surprisingly, placentation and carcinogenesis exhibit numerous shared features in metabolism and cell behavior, proteins and molecular signatures, signaling pathways, and tissue microenvironment, which proposes the concept of "cancer as ectopic trophoblastic cells". By extensive researches in this novel field, a handful of cancer biomarkers has been discovered. This review paper, which has been inspired in part by our extensive experiences during the past couple of years, highlights new aspects of placental functions with emphasis on its immunomodulatory role in establishment of a successful pregnancy and on a potential link between placentation and carcinogenesis.
Topics: Humans; Pregnancy; Female; Placenta; Animals; Placentation; Endometrium; Neoplasms; Embryo Implantation
PubMed: 38707901
DOI: 10.3389/fimmu.2024.1385762 -
Reproduction in Domestic Animals =... Sep 2023Methods to diagnose and monitor equine pregnancy continue to advance with improved instrumentation enabling the development of novel, non-invasive approaches to assess... (Review)
Review
Methods to diagnose and monitor equine pregnancy continue to advance with improved instrumentation enabling the development of novel, non-invasive approaches to assess fetal well-being and viability using ultrasound and endocrine testing. From early embryonic loss to placentitis, that is typically encountered later in gestation, fetal viability and development as well as placental function can be evaluated using two fundamentally different, structural and functional, approaches. Ultrasound provides structural information on embryonic and fetal growth using such parameters as combined thickness of the uterus and placenta (CTUP), visual assessment of fetal fluids, activity, heart rate and multiple biometrics involving the fetal head and eyes, limbs and joints among many others, depending on the stage of gestation. Endocrine profiles that include progesterone and 5α-dihydroprogesterone, other metabolites, androgens and estrogens can be evaluated simultaneously using liquid chromatography-tandem mass spectrometry (LC-MS/MS) providing more functional information on fetal and placental competence and development. Endocrine information can be used in making clinical decisions including the need for progestin supplementation or when it can cease, and even estimating gestational stage in mares that cannot be easily palpated or scanned, as with mini-breeds or rancorous animals most notably. When used together, monitoring gestation by ultrasound and hormonal analysis provides unusual insight into feto-placental well-being and the progress of pregnancy, helping to identify problems needing therapeutic intervention.
Topics: Pregnancy; Horses; Animals; Female; Placenta; Chromatography, Liquid; Tandem Mass Spectrometry; Progesterone; Fetal Development
PubMed: 37191550
DOI: 10.1111/rda.14392 -
ACS Sensors Jul 2023Serving as the interface between fetal and maternal circulation, the placenta plays a critical role in fetal growth and development. Placental exosomes are small... (Review)
Review
Serving as the interface between fetal and maternal circulation, the placenta plays a critical role in fetal growth and development. Placental exosomes are small membrane-bound extracellular vesicles released by the placenta during pregnancy. They contain a variety of biomolecules, including lipids, proteins, and nucleic acids, which can potentially be biomarkers of maternal diseases. An increasing number of studies have demonstrated the utility of placental exosomes for the diagnosis and monitoring of pathological conditions such as pre-eclampsia and gestational diabetes. This suggests that placental exosomes may serve as new biomarkers in liquid biopsy analysis. This review provides an overview of the current understanding of the biological function of placental exosomes and their potential as biomarkers of maternal diseases. Additionally, this review highlights current barriers and the way forward for standardization and validation of known techniques for exosome isolation, characterization, and detection. Finally, microfluidic devices for exosome research are discussed.
Topics: Pregnancy; Female; Humans; Placenta; Exosomes; Liquid Biopsy; Biomarkers
PubMed: 37449399
DOI: 10.1021/acssensors.3c00689 -
Archives of Biochemistry and Biophysics Aug 2023Preeclampsia is a potentially life-threatening condition that can arise due to poor placentation and consequent abnormal uterine spiral artery remodeling. Abnormal...
Preeclampsia is a potentially life-threatening condition that can arise due to poor placentation and consequent abnormal uterine spiral artery remodeling. Abnormal placentation, in turn, is associated with aberrant trophoblast cell proliferation and apoptosis. Here, we investigated the lncRNA MALAT1 in trophoblast proliferation during early-onset preeclampsia (ePE). MALAT1 levels were examined in placental tissue samples from ePE patients and control patients. The effects and underlying mechanism of MALAT1 on proliferation, migration, invasion and apoptosis were investigated in the first-trimester extravillous trophoblast HTR-8/SVneo cells and the human choriocarcinoma JAR cells. MALAT1 levels were decreased in the placental tissue samples of ePE patients compared with those of control patients, and the levels of MALAT1 were positively correlated with the neonate birth-weight. Knockdown of MALAT1 attenuated the cell viability, proliferation, migration, invasion and the cell cycle progression of trophoblasts, but promoted the apoptosis of trophoblasts. The MALAT1 knockdown promoted miR-101-3p upregulation and VEGFA downregulation. Inhibitor of miR-101-3p increased vascular endothelial growth factor A (VEGFA) expression, and miR-101-3p mimic inhibited VEGFA expression. Luciferase assays showed that miR-101-3p could bind to both MALAT1 and VEGFA. The MALAT1 knockdown-induced induction in the cell vitality and proliferation were attenuated by miR-101-3p inhibitor. We conclude that endogenous MALAT1 promotes proliferation, migration and invasion of trophoblasts by inhibiting the miR-101-3p expression and the subsequent VEGFAupregulation. The reduced MALAT1 level in placental tissue may be involved in the pathogenesis of the ePE.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Trophoblasts; MicroRNAs; Placenta; Vascular Endothelial Growth Factor A; RNA, Long Noncoding; Pre-Eclampsia; Phenotype; Cell Proliferation; Cell Movement
PubMed: 37437834
DOI: 10.1016/j.abb.2023.109692 -
Pflugers Archiv : European Journal of... Jul 2023Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally... (Review)
Review
Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally defined as hypertension and may be accompanied by other end organ damages including proteinuria, maternal organ disturbances including renal insufficiency, neurological complications, thrombocytopenia, impaired liver function, or uteroplacental dysfunction such as fetal growth restriction and stillbirth. Although the causes of these hypertensive disorders of pregnancy are multifactorial and elusive, they seem to share some common vascular-related mechanisms, including diseased spiral arteries, placental ischemia, and endothelial dysfunction. Recently, preeclampsia is being considered as a vascular disorder. Unfortunately, due to the complex etiology of preeclampsia and safety concerns on drug usage during pregnancy, there is still no effective pharmacological treatments available for preeclampsia yet. An emerging area of interest in this research field is the potential beneficial effects of dietary intervention on reducing the risk of preeclampsia. Recent studies have been focused on the association between deficiencies or excesses of some nutrients and complications during pregnancy, fetal growth and development, and later risk of cardiovascular and metabolic diseases in the offspring. In this review, we discuss the involvement of placental vascular dysfunction in preeclampsia. We summarize the current understanding of the association between abnormal placentation and preeclampsia in a vascular perspective. Finally, we evaluate several studied dietary supplementations to prevent and reduce the risk of preeclampsia, targeting placental vascular development and function, leading to improved pregnancy and postnatal outcomes.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Placenta; Hypertension, Pregnancy-Induced; Placentation; Dietary Supplements
PubMed: 37043045
DOI: 10.1007/s00424-023-02810-2 -
Cell Communication and Signaling : CCS Dec 2023Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development,... (Review)
Review
Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal-fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal-fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal-fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications. Video Abstract.
Topics: Pregnancy; Female; Humans; Placenta; Trophoblasts; Transcription Factors; Adaptor Proteins, Signal Transducing; Pregnancy Complications
PubMed: 38098027
DOI: 10.1186/s12964-023-01371-2