OR03: TNFa signaling in the endometrial stroma promotes trophoblast invasion

2021 ◽  
Vol 85 (S1) ◽  
pp. 50-50
Keyword(s):  
Trophoblast Invasion ◽  
Endometrial Stroma

scholarly journals TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan You ◽  
Patrick Stelzl ◽  
Dana N. Joseph ◽  
Paulomi B. Aldo ◽  
Anthony J. Maxwell ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Endometrial Stroma ◽  
Relative Contribution ◽  
Tnf Α ◽  
Invasive Capacity ◽  
Trophoblast Migration

Successful implantation requires the coordinated migration and invasion of trophoblast cells from out of the blastocyst and into the endometrium. This process relies on signals produced by cells in the maternal endometrium. However, the relative contribution of stroma cells remains unclear. The study of human implantation has major technical limitations, therefore the need of in vitro models to elucidate the molecular mechanisms. Using a recently described 3D in vitro models we evaluated the interaction between trophoblasts and human endometrial stroma cells (hESC), we assessed the process of trophoblast migration and invasion in the presence of stroma derived factors. We demonstrate that hESC promotes trophoblast invasion through the generation of an inflammatory environment modulated by TNF-α. We also show the role of stromal derived IL-17 as a promoter of trophoblast migration through the induction of essential genes that confer invasive capacity to cells of the trophectoderm. In conclusion, we describe the characterization of a cellular inflammatory network that may be important for blastocyst implantation. Our findings provide a new insight into the complexity of the implantation process and reveal the importance of inflammation for embryo implantation.

Morphological and immunohistochemical especially of stilled pregnancy the first trimester

2014 ◽  
Vol 63 (4) ◽  
pp. 60-68
Author(s):  
Tat’yana Georgievna Tral ◽  
Gulrukhsor Khaybulloevna Tolibova
Keyword(s):  
Estrogen Receptor ◽  
Menstrual Cycle ◽  
Histological Examination ◽  
Gestational Age ◽  
First Trimester ◽  
Trophoblast Invasion ◽  
Endometrial Stroma ◽  
First Trimester Of Pregnancy ◽  
Complete Transformation

Results of histological examination showed that stilled pregnancy occurs not only when the incomplete transformation of endometrial stroma, but also in terms of its full maturation regardless of hormonal support to maintain pregnancy. With increasing gestational age, regardless of hormonal support of pregnancy complete transformation of the endometrium occurs significantly more frequently. Furthermore, role hormonal drugs is not critical for the formation of endometrial glandular system. Increased expression of estrogen receptor in the glands and stroma of endometrium during pregnancy indicate the pathology of the first phase of the menstrual cycle. The reduction of the expression of KISS1 in endometrium during pregnancy was observed by the end of the first trimester of pregnancy due to the fading of the first stage of trophoblast invasion.

ÜBER DIE BILDUNG VON ENDOMETRIALEN KÖRNCHENZELLEN BEI KASTRATINNEN UNTER HORMONEINFLUSS

1960 ◽  
Vol XXXIII (II) ◽  
pp. 261-276 ◽  
Author(s):  
G. Hellweg ◽  
J. Ferin ◽  
K. G. Ober
Keyword(s):  
Hormone Therapy ◽  
Stromal Cells ◽  
Sex Hormone ◽  
Substitution Therapy ◽  
Secretory Phase ◽  
Hormone Substitution ◽  
Endometrial Stromal Cells ◽  
Endometrial Stroma ◽  
K Cells

ABSTRACT 65 endometrial biopsies from castrated women who had received either natural or artificial sex hormone therapy were studied microscopically. Attention was paid to various histologic criteria, especially to the number of endometrial granulocytes (»K« cells, KZ). The following was obtained: The »K« cells are completely absent when no hormone substitution therapy is given. They were also lacking when the castrated patients were treated only with oestrogens, even if the dose given was ten-times that found in women during the reproductive ages. In contrast, the »K« cells developed from the endometrial stromal cells only under influence of progesterone, usually appearing first 8–10 days after the administration of the gestagen. The »K« cells were demonstrable in the number corresponding to a normal secretory phase only then, when the oestrogen-progesterone dosage ratio had induced a fully-developed secretory change, as measured by the usual histologic criteria. With an overdosage of oestrogen the »K« cells were either absent or were very sparse. Contrarily, an overdosage of progesterone had no influence on their number. The development of endometrial glands does not always entirely parallel that of the stroma in castrated patients following hormone therapy. A more exact indicator for the proper dose for the production of a secretory phase by hormone therapy seems to be the number of »K« cells in the endometrial stroma.

scholarly journals Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities

2020 ◽  
Vol 22 (1) ◽  
pp. 165
Author(s):  
Lucía Pérez-Roque ◽  
Elena Núñez-Gómez ◽  
Alicia Rodríguez-Barbero ◽  
Carmelo Bernabéu ◽  
José M. López-Novoa ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Ex Vivo ◽  
Clinical Manifestations ◽  
High Plasma ◽  
Trophoblast Invasion ◽  
Future Research ◽  
Soluble Factors ◽  
Human Trophoblast ◽  
Soluble Endoglin ◽  
Pregnant Mice

Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.

scholarly journals ANXA4 promotes trophoblast invasion via the PI3K/Akt/eNOS pathway in preeclampsia

2019 ◽  
Vol 316 (4) ◽  
pp. C481-C491 ◽  
Author(s):  
Yalan Xu ◽  
Lili Sui ◽  
Bintao Qiu ◽  
Xiuju Yin ◽  
Juntao Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blotting ◽  
Underlying Mechanism ◽  
Trophoblast Invasion ◽  
Pathological Examination ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Annexin A4 ◽  
Extravillous Cytotrophoblasts ◽  
Phosphoinositide 3 Kinase

The inadequate trophoblast invasion is associated with the development of preeclampsia (PE). Considering that annexin A4 (ANXA4) enhances tumor invasion, we aimed to explore the functional role of ANXA4 in trophoblast cells and to examine the underlying mechanism. ANXA4 expression in PE placentas was analyzed using immunohistochemistry and Western blotting. Cell proliferation, invasion, and apoptosis were determined using a MTT assay, Transwell assay, and flow cytometry, respectively. The expression levels of matrix metalloproteinase (MMP)-2, MMP-9, phosphoinositide 3-kinase (PI3K), Akt, phosphorylated (p)-Akt, and phosphorylated endothelial nitric oxide synthase (p-eNOS) were detected by Western blotting. Placentas were prepared for pathological examination using hematoxylin and eosin staining and apoptosis determination using the TUNEL method. Expression of ANXA4, PI3K, p-Akt and p-eNOS was downregulated in human PE placentas and PE placenta-derived extravillous cytotrophoblasts (EVCTs). Furthermore, ANXA4 overexpression promoted cell proliferation and invasion, inhibited cell apoptosis, and upregulated protein expression of PI3K, p-Akt, and p-eNOS in human trophoblast cells HTR-8/SVneo and JEG-3. By contrast, ANXA4 knockdown exerted the opposite effects. Furthermore, inhibition of the PI3K/Akt pathway by LY294002 abrogated the ANXA4 overexpression-mediated effects on trophoblast behavior. Furthermore, eNOS knockdown abrogated the ANXA4 overexpression-induced promotion of cell invasion and MMP2/9 expression. Additionally, in N-nitro-l-arginine methyl ester (l-NAME)-induced PE rats, ANXA4 overexpression alleviated PE progression, accompanied by an increase in expression of PI3K, p-Akt, and p-eNOS in rat placentas. Our findings demonstrate that ANXA4 expression is downregulated in PE. ANXA4 may promote trophoblast invasion via the PI3K/Akt/eNOS pathway.

scholarly journals Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiao-Hui Wang ◽  
Sha Xu ◽  
Xiang-Yu Zhou ◽  
Rui Zhao ◽  
Yan Lin ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Embryo Implantation ◽  
Underlying Mechanism ◽  
Recurrent Spontaneous Abortion ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Iron Sulfur ◽  
Succinate Dehydrogenase Complex ◽  
Extravillous Trophoblasts ◽  
Control Study

AbstractDysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.

scholarly journals Prostaglandins and the initiation of blastocyst implantation and decidualization

Reproduction ◽  
2007 ◽  
Vol 134 (5) ◽  
pp. 635-643 ◽  
Author(s):  
Thomas G Kennedy ◽  
Carolina Gillio-Meina ◽  
Sen Han Phang
Keyword(s):  
Vascular Permeability ◽  
Trophoblast Invasion ◽  
Considerable Evidence ◽  
Blastocyst Implantation

The process of blastocyst implantation in mammals is remarkably variable, especially in the extent of trophoblast invasion of the endometrium. In most species studied, the earliest macroscopically identifiable sign of blastocyst implantation is an increase in endometrial vascular permeability in areas adjacent to the blastocysts. This is followed in species with invasive implantation by decidualization, again localized to areas adjacent to the blastocysts. In some species, the application of a stimulus to the endometrium can result in increased endometrial vascular permeability and decidualization. Based initially on studies utilizing inhibitors of prostaglandin (PG) synthesis and more recently on studies using the techniques of transgenics, considerable evidence has accumulated indicating that PGs have an important role in the early events of implantation and artificially induced decidualization. However, which PGs are involved remains controversial. There may be differences between species, and different PGs may be involved at different times.

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