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Frontiers in Nutrition 2023Imprinted genes are important for the offspring development. To assess the relationship between obesity-related methylation and and gene expression and offspring...
BACKGROUND AND OBJECTIVE
Imprinted genes are important for the offspring development. To assess the relationship between obesity-related methylation and and gene expression and offspring growth and body composition.
METHODS
Thirty-nine overweight/obese and 25 normal weight pregnant women were selected from the "Araraquara Cohort Study" according to their pre-pregnancy BMI. Fetal growth and body composition and newborn growth were assessed, respectively, by ultrasound and anthropometry. The methylation of in maternal blood, cord blood, maternal decidua and placental villi tissues was evaluated by methylation-sensitive restriction endonuclease qPCR, and and expression by relative real-time PCR quantification. Multiple linear regression models explored the associations of DNA methylation and gene expression with maternal, fetal, and newborn parameters.
RESULTS
was less methylated in maternal blood of the overweight/obese group. There were associations of methylation in cord blood with centiles of fetal biparietal diameter (BPD) and abdominal subcutaneous fat thickness and newborn head circumference (HC); methylation in maternal decidua with fetal occipitofrontal diameter (OFD), HC, and length; methylation in placental villi with fetal OFD, HC and abdominal subcutaneous fat thickness and with newborn HC. expression in maternal decidua was associated with fetal BPD and femur length centiles and in placental villi with fetal OFD and subcutaneous arm fat. expression in maternal decidua was associated with fetal BPD and in placental villi with fetal OFD.
CONCLUSION
To our knowledge, this is the first study to demonstrate associations of imprinted genes variations at the maternal-fetal interface of the placenta and in cord blood with fetal body composition, supporting the involvement of epigenetic mechanisms in offspring growth and body composition.
PubMed: 37810933
DOI: 10.3389/fnut.2023.1170411 -
The Journal of Maternal-fetal &... Dec 2023Unexplained recurrent pregnancy loss has been a a challenging research task to experts since there is no explicit pathophysiological mechanism and therefore, the...
BACKGROUND AND AIM
Unexplained recurrent pregnancy loss has been a a challenging research task to experts since there is no explicit pathophysiological mechanism and therefore, the treatment remains elusive. Immunological imbalance and morphological abnormalities are under investigation. This study aims to evaluate the implication of MMP-2, MMP-9, EGFR, and IL-8 in recurrent pregnancy loss cases.
MATERIALS & METHODS
The study was carried out through comparison among two groups; the unexplained miscarriage group which consisted of 22 women, and the control group consisted of 18 women, who had electively terminated their pregnancies. Both groups were in the first trimester of gestation. The specimens included the trophoblast, decidua basalis, and decidua parietalis. The study was conducted immunohistochemical methods. Antibodies were used against MMP-2, MMP-9, EGFR, and IL-8. The results were presented at a contingency table and were statistically analyzed with the Chi-Square Test (X).
RESULTS
There were remarkable disparities in some cases in the comparison of the two groups. MMP-9 was detected significantly high in recurrent pregnancy loss (RPL) cases, both on trophoblastic and decidual specimens (-value < .00001), MMP-2 displayed no difference among the two groups (mild to moderate detection on trophoblast and almost negative on decidual tissues). EGFR was highly detected in trophoblastic tissue (-value = .014). IL-8 detection was particularly different in both trophoblast and decidua parietalis of the two groups (-value < .01).
CONCLUSION
The study revealed both morphological and immunological dysregulations that might participate in the RPL pathogenesis.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Decidua; ErbB Receptors; Interleukin-8; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Pregnancy Trimester, First; Trophoblasts
PubMed: 37258409
DOI: 10.1080/14767058.2023.2218523 -
ELife Jul 2023Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a...
Gαq-PKD/PKCμ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy.
Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of , which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCμ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCμ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine's expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy.
Topics: Pregnancy; Female; Humans; NF-kappa B; Decidua; Active Transport, Cell Nucleus; Protein Kinase C; GTP-Binding Proteins; Stromal Cells; Histone Deacetylases
PubMed: 37498654
DOI: 10.7554/eLife.83083 -
Medicine Aug 2023Preeclampsia is a pregnancy complication Aim of this study was to investigate expression of Beclin1 and tumor necrosis factor (TNF)-α in normotensive and preeclamptic...
BACKGROUND
Preeclampsia is a pregnancy complication Aim of this study was to investigate expression of Beclin1 and tumor necrosis factor (TNF)-α in normotensive and preeclamptic placentas of pregnant women patients.
METHODS
Twenty normotensive and 20 preeclamptic patients placentas were dissected for paraffin- wax processing. Placental samples were embedded in parafin blocks. Sections were stained with Hematoxylin-Eosin staining and TNF-α and Beclin1 immunostaining.
RESULTS
In control group, root and floating villi were normal in histological perspectives, syncytial node number was low, vessels were normal with connective tissue. No hemorrhage was observed in the intervillous area. In preeclampsia group, decidual cell degeneration and fibrinoid accumulation increased. Vascular dilatation and congestion with mononuclear cell infiltration were observed. Beclin1 reaction was generally negative in control group. In preeclampsia group, Beclin1 reaction was increased in decidual cells, syncytial nodes and bridges and in chorionic villi and in some Hoffbauer cells. In control group, TNF-α expression was mainly negative but only in some decidual cells. In preeclampsia, TNF-α reaction was observed in degenerated decidua cells, in leukocytes and in villi.
CONCLUSION
In preeclampsia placentas, degenerated decidua cells and inflammation increased. It was thought that Beclin1 and TNF-α signals could be used as a marker in affecting the fetal structure of blood flow in preeclamptic placentas.
Topics: Female; Humans; Pregnancy; Beclin-1; Chorionic Villi; Placenta; Pre-Eclampsia; Tumor Necrosis Factor-alpha
PubMed: 37603530
DOI: 10.1097/MD.0000000000034757 -
International Journal of Surgical... Oct 2023Hypertensive disorders of pregnancy continue to pose the most important risks for adverse maternal and neonatal outcome. Among histological findings, decidual artery...
Hypertensive disorders of pregnancy continue to pose the most important risks for adverse maternal and neonatal outcome. Among histological findings, decidual artery disease is one of the most common, one that has both good reproducibility among observers and whose abnormal vascular remodeling is the sole aspect of preeclampsia pathophysiology on which experts agree. Nevertheless, some aspects of arterial remodeling alterations are still under investigation. We selected 720 routine and consecutive placenta case studies, concordant with the Amsterdam consensus. From these studies, we collected maternal and neonatal clinical data and specific placental findings on spiral artery abnormalities. We took into account all criteria for decidual arteriopathy. Two hundred and fifteen (215) cases out of this population presented hypertensive disorders of pregnancy. Additional to expected arterial findings, we noted frequent persistent parietal trophoblast lining. A large proportion of our population developed hypertensive disorders of pregnancy (30%). Among the histologic findings reported for preeclampsia, we paid particular attention to spiral artery abnormalities, and this interpretive analysis revealed high frequency of arterial remodeling abnormalities. We examined two additional aspects in our routine analysis: first, the novel one of parietal trophoblast persistence, and second, the established problem of associated acute inflammation, as a possible pitfall. In order to better understood, spiral maternal artery remodeling merits further study. The abnormalities in this process provide an objective tool in the study and diagnosis of important pregnancy complications; furthermore, abnormal remodeling is an expression of early pregnancy alteration, and subsequently related to preeclampsia etiology.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placenta; Decidua; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Reproducibility of Results; Trophoblasts; Vascular Diseases; Arteries
PubMed: 36471503
DOI: 10.1177/10668969221140386 -
Current Issues in Molecular Biology Nov 2023Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is...
Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is involved in various eosinophilic diseases. Since increased galectin expression is already detected in the placentas of mothers with gestational diabetes mellitus (GDM), this study focuses on the specific role of galectin-10 and hints at consequences for the diagnosis and therapeutic options of GDM. It is hypothesized that the difference in galectin-10 expression will raise the pathophysiological understanding of gestational diabetes. The study population consists of 80 women: 40 healthy mothers and 40 women suffering from gestational diabetes mellitus. The expression of galectin-10 was analyzed in the syncytiotrophoblast (SCT) and the decidua of the placenta via immunohistochemistry and immunofluorescence double staining. The immunoreactivity score (IRS) was used for evaluation. The results in this study were significant for an overexpression of galectin-10 in GDM placentas compared with the control group. The syncytiotrophoblast showed overexpression in the nucleus and the cytoplasm, whereas expression of galectin-10 in the decidua was significant in the cytoplasm only. This study identified the expression changes in galectin-10 in placental tissue between healthy and GDM mothers and intensified the understanding of gestational diabetes. Assuming that gestational diabetes mellitus is involved in inflammatory processes, galectin-10 might play a role in the development and maintenance of GDM. Further investigation is required to strengthen these findings.
PubMed: 37998731
DOI: 10.3390/cimb45110554 -
Tissue & Cell Jun 2024GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-β signaling is critical for placental...
GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-β signaling is critical for placental development and can interact with GATA3. We aimed to investigate the involvement of the multifunctional cytokine and transcription factor in trophoblast development. By using immunohistochemistry, we evaluated the localization and expression level of GATA3 and TGF-β in placentas at term of normal pregnancy and with pre-eclampsia. Up-regulation of both GATA3 and TGF-β was observed in pathological placentas, with localization in the villus epithelium (syncytiotrophoblast) stroma and decidua. Our data show altered expression of TGF-β and GATA3, which downstream could lead to a cascade of events that negatively influence trophoblast development and contribute to the pathogenesis of pre-eclampsia.
Topics: Pre-Eclampsia; Humans; Pregnancy; Female; GATA3 Transcription Factor; Placenta; Transforming Growth Factor beta; Adult; Trophoblasts
PubMed: 38759523
DOI: 10.1016/j.tice.2024.102402 -
Archives of Gynecology and Obstetrics Sep 2023Miscarriage is one of the most common complications of pregnancy. Although chromosomal abnormalities of the embryo is a well-known cause of miscarriage, a lot of cases...
PURPOSE
Miscarriage is one of the most common complications of pregnancy. Although chromosomal abnormalities of the embryo is a well-known cause of miscarriage, a lot of cases remain unexplained, with immunologic and vascular growth alterations being considered as probable causes. Chemokines are produced by a variety of cells and exhibit several functions including both pro and anti-angiogenic properties. In this study, we investigated the role of the angiogenic and angiostatic chemokines in placenta and decidua tissues from spontaneous and induced abortions.
METHODS
Total RNA was extracted from the placenta and decidua tissues, which was then purified and converted into cDNA. Real-time PCR was then performed for the expression of the angiogenic CCL2, CCL5, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8 and CXCL4, and the angiostatic CXCL9, CXCL10, CXCL11, CXCL12 and CXCL14 and results were then statistically analyzed.
RESULTS
Regarding the placenta, CXCL7 (2.29-fold, 2.16-2.38, p < 0.05), CXCL4 (1.01-fold, 0.74-4.447, p < 0.05), CXCL9 (0.87-fold, 0.43-1.34, p < 0.05) and CXCL11 (0.31-fold, 0.22-0.45, p < 0.05) were altered in spontaneous abortions. CCL2, CCL5, CXCL2-3, CXCL8, CXCL10, CXCL12 and CXCL14 were not statistically significant altered. Regarding the decidua, CXCL7 (7.13-fold, 6.32-7.54, p < 0.01), CXCL8 (11.02-fold, 8.58-13.45, p < 0.05), CCL20 (1.21-fold, 0.29-1.89, p < 0.05) and CXCL9 (5.49-fold, 3.67-6.39, p < 0.05) were overexpressed in spontaneous abortions. CXCL2-4, CCL2, CCL5, CXCL10-12 and CXCL14 did not show any differences. The expression of the chemokines CXCL1, CXCL5-6 was absent in either tissue or group.
CONCLUSION
Our results show that the overexpression of angiostatic and diminished expression of angiogenic chemokines takes place in the placenta and decidua of spontaneous abortions, suggesting that dysregulation of angiogenesis could be a contributive factor to the pathogenesis of miscarriage.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Placenta; Decidua
PubMed: 35997970
DOI: 10.1007/s00404-022-06725-8 -
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 -
Communications Biology Feb 2024Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered...
Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our study reveals that transforming growth factor β (TGFβ) pathways are impaired in the endometrium of individuals with endometriosis, leading to defective decidualization. Through detailed transcriptomic analyses, we discovered abnormalities in TGFβ signaling pathways and key regulators, such as SMAD4, in the endometrium of affected individuals. We also observed compromised activity of bone morphogenetic proteins (BMP), a subset of the TGFβ family, that control endometrial receptivity. Using 3-dimensional models of endometrial stromal and epithelial assembloids, we showed that exogenous BMP2 improved decidual marker expression in individuals with endometriosis. Our findings reveal dysfunction of BMP/SMAD signaling in the endometrium of individuals with endometriosis, explaining decidualization defects and subsequent pregnancy complications in these individuals.
Topics: Pregnancy; Female; Humans; Endometriosis; Decidua; Bone Morphogenetic Proteins; Transforming Growth Factor beta; Signal Transduction; Infertility; Pregnancy Complications
PubMed: 38402336
DOI: 10.1038/s42003-024-05898-z