Ultrastructural alterations in human decidua in miscarriages compared to normal pregnancy decidua

Kara, Fadıl; Cınar, Ozgur; Erdemli-Atabenli, E.; Sabuncuoğlu, Bizden; Can, Alp

doi:10.1080/00016340701505457

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…Reduced CX43 expression and GJIC function in the endometrium have pathological consequences, including impaired angiogenesis, implantation failure, and pregnancy loss (Kara et al, ; Laws et al, ; Nair et al, ), and are a feature of endometriosis (Regidor et al, ; Yu et al, ). In the current study, we confirmed that an important mechanism by which gap junction blockade disrupts endometrial function is via stromal cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Gap junction blockade induces apoptosis in human endometrial stromal cells

Berga

Zou

et al. 2014

Molecular Reproduction Devel

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One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17β-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies.

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Section: Discussionmentioning

confidence: 99%

Gap junction blockade induces apoptosis in human endometrial stromal cells

Berga

Zou

et al. 2014

Molecular Reproduction Devel

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“…Analysis of decidual cells from miscarriage by scanning electron microscope (SEM) and a transmission electron microscope (TEM) revealed a moderate degree of degeneration, a decreased number of junctional complexes and an increased number of NK cells. This finding suggests a lack of intercellular communication, a phenomenon which obviously alters proper implantation and leads to the induction of embryonic disgenesis and miscarriage 74 …”

Section: Endometrial/decidual Nk Cellsmentioning

confidence: 99%

REVIEW ARTICLE: Clinical Implication of Natural Killer Cells and Reproduction

Kwak‐Kim

Gilman‐Sachs

2008

American J Rep Immunol

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The regulation of natural killer (NK) cells in the peripheral blood and endometrial layers has been associated with reproductive immunopathology such as recurrent spontaneous abortions (RSA), infertility of implantation failures, or pre‐eclampsia. The placenta has a complex anatomical structure and different subsets of NK cells with various functional roles can directly interact with trophoblasts. NK cell subpopulations and their functions, putative roles of NK cells in peripheral blood and endometrium are reviewed in relation to RSA and infertility. An increase in NK cell numbers and /or activity in pre‐ or post‐conceptional period in women with RSA or infertility with multiple implantation failures are a significant clinical concern. In addition, immuno‐phenotypic characteristics of NK cells in these women support the changes for their increased activity status. Further studies are needed to explore underlying mechanism of NK cells in RSA, infertility, and other reproductive immunopathologies. Possible neurological and hormonal control of NK cells and NK cell interaction with various leukocyte populations need further investigation in women with reproductive failures.

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“…[33] For women with miscarriage, decidual cells obtained through curettage have significantly lower levels of GJ expression in women who terminate pregnancy but have no other abnormalities. [34] If GJA1 is knocked out in the endometrial stroma, the embryo will not continue to grow, and it can be considered that GJA1 can significantly affect the pregnancy process in the early stages of pregnancy. [35] Researchers such as He et al [36] found that recurrent pregnancy loss women have significantly lower levels of Cx43 expression.…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of biomarkers associated with oxidative stress and ferroptosis in recurrent miscarriage

Xie,

Zhu,

Zhao

et al. 2024

Medicine

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Recurrent miscarriage (RM) has a huge impact on women. Both oxidative stress and ferroptosis play an important role in the pathogenesis of RM. Hence, it was vital to screen the ferroptosis oxidation-related biomarkers for the diagnosis and treatment of RM. We introduced transcript data to screen out differentially expressed genes (DEGs) in RM. Ferroptosis oxidation-related differentially expressed genes were obtained by overlapping DEGs and oxidative stress related genes with correlations >0.9 with ferroptosis-related genes. Least Absolute Shrinkage and Selectionator operator regression and support vector machine based recursive feature elimination algorithm were implemented to screen feature genes. The biomarkers associated with ferroptosis oxidation were screened via receiver operating characteristic curve analysis. We finally analyzed the competing endogenous RNAs regulatory network and potential drugs of biomarkers. We identified 1047 DEGs in RM. Then, 9 ferroptosis oxidation-related differentially expressed genes were obtained via venn diagram. Subsequently, 8 feature genes (PTPN6, GJA1, HMOX1, CPT1A, CREB3L1, SNCA, EPAS1, and TGM2) were identified via machine learning. Moreover, 4 biomarkers associated with ferroptosis oxidation, including PTPN6, GJA1, CPT1A, and CREB3L1, were screened via receiver operating characteristic curve analysis. We constructed the ‘227 long noncoding RNAs-4 mRNAs-36 microRNAs’ network, in which hsa-miR-635 was associated with CREB3L1 and PTPN6. There were 11 drugs with therapeutic potential on 3 biomarkers associated with ferroptosis oxidation. We also observed higher expression of CPT1A and CREB3L1 in RM group compared to the healthy control group by quantitative real-time reverse transcription polymerase chain reaction. Overall, we obtained 4 biomarkers (PTPN6, GJA1, CPT1A, and CREB3L1) associated with ferroptosis and oxidative stress, which laid a theoretical foundation for the diagnosis and treatment of RM.

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Ultrastructural alterations in human decidua in miscarriages compared to normal pregnancy decidua

Cited by 11 publications

References 36 publications

Gap junction blockade induces apoptosis in human endometrial stromal cells

Gap junction blockade induces apoptosis in human endometrial stromal cells

REVIEW ARTICLE: Clinical Implication of Natural Killer Cells and Reproduction

Identification and analysis of biomarkers associated with oxidative stress and ferroptosis in recurrent miscarriage

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