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Epigenetics Dec 2024Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from...
Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased expression. Increased expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Decidua; DNA Methylation; Macrophages; Phagocytosis; Up-Regulation
PubMed: 38564758
DOI: 10.1080/15592294.2024.2337087 -
Journal of Reproductive Immunology Jun 2024Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to... (Review)
Review
Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to complicate approximately 2-8% of pregnancies worldwide. PE is a prominent medical disorder that poses a significant risk to pregnant mothers and their infants. This review commences by giving the most up-to- date concepts about the pathophysiology of PE. The condition involves atypical infiltration of trophoblast cells into the spiral arteries of the decidua and myometrium, resulting in an insufficient establishment of proper blood flow between the uterus and placenta. The aberrant activation of natural killer (NK) cells in both the peripheral blood and the decidua has been identified as one of the contributing factors to the development of PE. The strong evidence for the genetic etiology of PE is provided by the association between maternal killer cell immunoglobulin-like receptor (KIR) and Human Leukocyte Antigen (HLA-C) in trophoblast cells. Recent observations provide evidence that changes in the expression of anti-angiogenic factors in the placenta are the underlying cause of the clinical symptoms associated with the condition. This review also provides a comprehensive overview of the latest advancements in understanding the underlying causes of PE. It specifically highlights the emergence of new diagnostic biomarkers and their potential implications for therapeutic interventions in managing this medical condition.
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Biomarkers; Killer Cells, Natural; Trophoblasts; Receptors, KIR; Placenta; HLA-C Antigens; Animals; Decidua
PubMed: 38555746
DOI: 10.1016/j.jri.2024.104236 -
Journal of Clinical Pathology Mar 2024A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to...
AIMS
A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.
METHODS
Over a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus.
RESULTS
Thirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases.
CONCLUSIONS
This study validates the use of D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.
PubMed: 38555105
DOI: 10.1136/jcp-2023-209269 -
Journal of Trace Elements in Medicine... Jul 2024Contamination with heavy metals (HM) has great environmental consequences in the environment due to lack of biodegradation, in addition, accumulation in living beings... (Review)
Review
STATEMENT OF PROBLEM
Contamination with heavy metals (HM) has great environmental consequences in the environment due to lack of biodegradation, in addition, accumulation in living beings causes defects in tissues and organs, deteriorating their function and inducing a wide spectrum of diseases. Human biomonitoring consists of the periodic measurement of a certain chemical substance or metabolite in a particular population, using matrices that can be acute or chronic. Teeth are chronic matrices that have great characteristics of resistance and chronological storage of information. This review aims to identify the mechanisms, spatial location, and affinity of HM within teeth, along with understanding its applicability as a chronological record matrix in the face of HM contamination.
MATERIAL AND METHODS
A systematic search review was performed using the PubMed/Medline, Web of Science, and Scopus metasearch engines, and the terms "teeth" OR "dental" OR "tooth" AND "heavy metals" were intersected. Complete articles are included in Spanish, English and Portuguese without time restrictions, involving studies in humans or in vitro; Letters to the editor, editorials and those that did not refer to information on the incorporation and relationship of HM with the teeth were excluded.
RESULTS
837 published articles were detected, 91 were adjusted to the search objective, and 6 were manually included. Teeth are structures with a great capacity for information retention in the face of HM contamination due to low physiological turnover and their long processes of marked formations by developmental biorhythm milestones such as the neonatal line (temporal reference indicator). The contamination mechanisms inside the tooth are linked to the affinity of hydroxyapatite for HM; this incorporation can be in the soft matrix during the apposition phase or as part of the chemical exchanges between hydroxyapatite and the elements of the environment.
CONCLUSION
The teeth present unique characteristics of great resistance and affinity for HM, as well as a chronological biomarker for human biomonitoring, so they can be used as means of expertise or evidence to confirm or rule out a fact of environmental characteristics in the legal field.
Topics: Humans; Biomarkers; Metals, Heavy; Tooth, Deciduous; Dentition, Permanent
PubMed: 38547726
DOI: 10.1016/j.jtemb.2024.127435 -
The Journal of Obstetrics and... Jun 2024The refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes... (Review)
Review
AIM
The refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes frozen embryo transfer (FET) an alternative to fresh ET and has contributed to the success of assisted reproductive technology. Compared with fresh ET cycles, FET cycles were associated with better in vitro fertilization outcomes; however, the occurrence of pregnancy-induced hypertension, preeclampsia, and placenta accreta spectrum (PAS) was higher in FET cycles. PAS has been increasing steadily in incidence as a life-threatening condition along with cesarean rates worldwide. In this review, we summarize the current understanding of the pathogenesis of PAS and discuss future research directions.
METHODS
A literature search was performed in the PubMed and Google Scholar databases.
RESULTS
Risk factors associated with PAS incidence include a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling, and abnormally invasive trophoblasts, or a combination thereof. Freezing, thawing, and hormone replacement manipulations have been shown to affect multiple cellular pathways, including cell proliferation, invasion, epithelial-to-mesenchymal transition (EMT), and mitochondrial function. Molecules involved in abnormal migration and EMT of extravillous trophoblast cells are beginning to be identified in PAS placentas. Many of these molecules were also found to be involved in mitochondrial biogenesis and dynamics.
CONCLUSION
The etiology of PAS may be a multifactorial genesis with intrinsic predisposition (e.g., placental abnormalities) and certain environmental factors (e.g., defective decidua) as triggers for its development. A distinctive feature of this review is its focus on the potential factors linking mitochondrial function to PAS development.
Topics: Humans; Placenta Accreta; Female; Pregnancy; Mitochondria
PubMed: 38544343
DOI: 10.1111/jog.15936 -
Microorganisms Mar 2024The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies...
The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging data suggest a dynamic interplay between endometrial microflora and the immune system, making dysbiosis a potential determinant of pregnancy outcomes. Imbalances in the regulation of immune cells in the endometrium and decidua have been associated with infertility, miscarriage, and obstetric complications. A thorough comprehension of the immune system in the female reproductive tract shows potential for improving women's health and pregnancy outcomes. The objective of this study was to evaluate the patterns of endometrial microbiota in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) and to explore their implications for endometrial immune cells and chronic endometritis (CE). Immune cells in biopsies from 107 RIF and 93 RPL patients were examined using flow cytometry. The endometrial microbial composition was analyzed using real-time polymerase chain reaction (RT-PCR). The research uncovered disrupted endometrial microbiota in most women with RIF and RPL, which was often associated with significant effects on lymphocytes, T cells, and uNK cells.
PubMed: 38543598
DOI: 10.3390/microorganisms12030547 -
International Journal of Molecular... Mar 2024Using an established human primary cell culture model, we previously demonstrated that the promyelocytic leukemia zinc finger (PLZF) transcription factor is a direct...
Using an established human primary cell culture model, we previously demonstrated that the promyelocytic leukemia zinc finger (PLZF) transcription factor is a direct target of the progesterone receptor (PGR) and is essential for progestin-dependent decidualization of human endometrial stromal cells (HESCs). These in vitro findings were supported by immunohistochemical analysis of human endometrial tissue biopsies, which showed that the strongest immunoreactivity for endometrial PLZF is detected during the progesterone (P4)-dominant secretory phase of the menstrual cycle. While these human studies provided critical clinical support for the important role of PLZF in P4-dependent HESC decidualization, functional validation in vivo was not possible due to the absence of suitable animal models. To address this deficiency, we recently generated a conditional knockout mouse model in which PLZF is ablated in PGR-positive cells of the mouse (). The female was phenotypically analyzed using immunoblotting, real-time PCR, and immunohistochemistry. Reproductive function was tested using the timed natural pregnancy model as well as the artificial decidual response assay. Even though ovarian activity is not affected, female mice exhibit an infertility phenotype due to an inability of the embryo to implant into the endometrium. Initial cellular and molecular phenotyping investigations reveal that the endometrium is unable to develop a transient receptive state, which is reflected at the molecular level by a blunted response to P4 exposure with a concomitant unopposed response to 17-β estradiol. In addition to a defect in P4-dependent receptivity, the endometrium fails to undergo decidualization in response to an artificial decidual stimulus, providing the in vivo validation for our earlier HESC culture findings. Collectively, our new mouse model underscores the physiological importance of the PLZF transcription factor not only in endometrial stromal cell decidualization but also uterine receptivity, two uterine cellular processes that are indispensable for the establishment of pregnancy.
Topics: Pregnancy; Female; Mice; Animals; Humans; Transcription Factors; Decidua; Endometrium; Mice, Knockout; Zinc Fingers; Leukemia; Stromal Cells
PubMed: 38542422
DOI: 10.3390/ijms25063451 -
Biology Mar 2024The etiopathogenesis of preeclampsia, a leading hypertensive disorder of pregnancy, has been proposed to involve an abnormal circulating sex hormone profile and...
The etiopathogenesis of preeclampsia, a leading hypertensive disorder of pregnancy, has been proposed to involve an abnormal circulating sex hormone profile and misexpression of placental estrogen and progesterone receptors (ER and PR, respectively). However, existing research is vastly confined to third trimester preeclamptic placentas. Consequently, the placental-uterine molecular crosstalk and the dynamic ER and PR expression pattern in the peri-conception period remain overlooked. Herein, our goal was to use the BPH/5 mouse to elucidate pre-pregnancy and early gestation Er and Pr dynamics in a preeclamptic-like uterus. BPH/5 females display low circulating estrogen concentration during proestrus, followed by early gestation hypoestrogenemia, hyperprogesteronemia, and a spontaneous preeclamptic-like phenotype. Preceding pregnancy, the gene encoding Er alpha (Erα, ) is upregulated in the diestrual BPH/5 uterus. At the peak of decidualization, , Er beta (Erβ, ), and Pr isoform B () were upregulated in the BPH/5 maternal-fetal interface. At the protein level, BPH/5 females display higher percentage of decidual cells with nuclear Erα expression, as well as Pr downregulation in the decidua, luminal and glandular epithelium. In conclusion, we provide evidence of disrupted sex hormone signaling in the peri-conception period of preeclamptic-like pregnancies, potentially shedding some light onto the intricate role of sex hormone signaling at unexplored timepoints of human preeclampsia.
PubMed: 38534461
DOI: 10.3390/biology13030192 -
Frontiers in Immunology 2024Zika virus (ZIKV) can be vertically transmitted during pregnancy resulting in a range of adverse pregnancy outcomes. The decidua is commonly found to be infected by...
Zika virus (ZIKV) can be vertically transmitted during pregnancy resulting in a range of adverse pregnancy outcomes. The decidua is commonly found to be infected by ZIKV, yet the acute immune response to infection remains understudied . We hypothesized that African-lineage ZIKV infection induces a pro-inflammatory response in the decidua. To test this hypothesis, we evaluated the decidua in pregnant rhesus macaques within the first two weeks following infection with an African-lineage ZIKV and compared our findings to gestationally aged-matched controls. Decidual leukocytes were phenotypically evaluated using spectral flow cytometry, and cytokines and chemokines were measured in tissue homogenates from the decidua, placenta, and fetal membranes. The results of this study did not support our hypothesis. Although ZIKV RNA was detected in the decidual tissue samples from all ZIKV infected dams, phenotypic changes in decidual leukocytes and differences in cytokine profiles suggest that the decidua undergoes mild anti-inflammatory changes in response to that infection. Our findings emphasize the immunological state of the gravid uterus as a relatively immune privileged site that prioritizes tolerance of the fetus over mounting a pro-inflammatory response to clear infection.
Topics: Pregnancy; Humans; Female; Animals; Zika Virus Infection; Zika Virus; Macaca mulatta; Pregnancy Complications, Infectious; Leukocytes
PubMed: 38515747
DOI: 10.3389/fimmu.2024.1363169 -
Journal of Assisted Reproduction and... Jun 2024The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between...
PURPOSE
The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity.
METHODS
Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored.
RESULTS
A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI.
CONCLUSION
MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity.
Topics: Female; MicroRNAs; Embryo Implantation; Humans; Mice; Stromal Cells; Endometrium; Animals; Pregnancy; Adult; Decidua; Homeobox A10 Proteins; Embryo Transfer
PubMed: 38512656
DOI: 10.1007/s10815-024-03088-8