transforming-growth-factor-beta and Placenta-Accreta

Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors contributing to trophoblast invasiveness and angiogenic potential, which in turn drive the pathogenesis of placenta accreta. We focused on the transforming growth factor (TGF)-β1-Smad pathway and investigated the intrinsic relationship between the time- and dose-dependent inhibition of the ubiquitinating enzyme UCHL5 using bAP15, a deubiquitinase inhibitor, after TGF-β1 stimulation and the invasive and angiogenic potential of two cell lines, gestational choriocarcinoma cell line JEG-3 and trophoblast cell line HTR-8/SVneo. UCHL5 inhibition negatively regulated TGF-β1-induced Smad2 activation, decreasing extravillous trophoblast invasiveness. Smad1/5/9 and extracellular signal-regulated kinase (ERK) were simultaneously activated, and vascular endothelial growth factor was secreted into the trophoblast medium. However, extravillous trophoblast culture supernatant severely impaired the vasculogenic potential of human umbilical vein endothelial cells. These results suggest that the downstream ERK pathway and Smad1/5/9 potentially regulate the TGF-β1-Smad pathway in extravillous trophoblasts, whereas Smad2 contributes to their invasiveness. The abnormal invasive and angiogenic capacities of extravillous cells, likely driven by the interaction between TGF-β1-Smad and ERK pathways, underlie the pathogenesis of placenta accreta.

Topics: Cell Line, Tumor; Cysteine Proteases; Extracellular Signal-Regulated MAP Kinases; Female; Human Umbilical Vein Endothelial Cells; Humans; Placenta Accreta; Pregnancy; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ubiquitin Thiolesterase; Vascular Endothelial Growth Factor A

Placenta accreta is a pregnancy-related disorder with extreme trophoblast invasion and the adherence of the placenta to the uterine wall. This study aimed to investigate the serum level of transforming growth factor-beta 1 (TGF-β1) and interleukin (IL)-35 in patients with placenta accreta.. Thirty-one women with placenta accreta and 57 healthy pregnant women were enrolled. The serum levels of TGF-β1 and IL-35 were measured using the enzyme-linked immunosorbent assay method.. The serum levels of both TGF-β and IL-35 were significantly higher in the placenta accreta group compared with the group of healthy women (1082.48 pg/mL vs 497.33 pg/mL and 4541.14 pg/mL vs 1306.04 pg/mL; P <.001, respectively). Moreover, the level of TGF-β1 positively correlated with the IL-35 level but other factors such as age, gestations, live births, and abortions did not correlate with IL-35 and TGF-β1 levels.. The serum levels of IL-35 and TGF-β1 may contribute to the pathogenesis of placenta accreta and could be considered as potential targets in clinical and diagnostic approaches.

Topics: Female; Humans; Interleukins; Placenta; Placenta Accreta; Pregnancy; Transforming Growth Factor beta; Transforming Growth Factor beta1

To investigate the expression profile of long non-coding RNAs (lncRNA) and identify potential lncRNA-related competing endogenous RNAs (ceRNA) in placenta accrete spectrum disorders (PAS).. Five tissue specimens of placental implantation and 5 adjacent normal placental tissues were collected from cesarean section deliveries complicated by PAS in our hospital between December, 2017 and June, 2018. Human microarrays were used to identify the lncRNAs that were differentially expressed in PAS, and 5 of the identified lncRNAs were further validated using qRT-PCR. GO and KEGG pathway analyses were performed to indentify the most significant enrichment functions. A ceRNA network was constructed based on ENST00000511361 (RP5-875H18.4), NR_027457 (LINC00221) and NR_126415 (FOXP4-AS1) to pinpoint the potential lncRNAs-related ceRNA.. A total of 329 lncRNAs and 179 mRNAs were identified to have differential expression in PAS. The results of qRT-PCR were consistent with the human microarrays results. Transforming growth factor-β (TGF-β) signaling pathway was the most significantly enriched pathway. The constructed ceRNA network suggested that RP5-875H18.4--miRNA-218--SLIT2 had a potential ceRNA regulatory mechanism in PAS.. The differentially expressed lncRNAs are involved in the occurrence and progression of PAS possibly by regulating the TGF-β signaling pathway. The ceRNA network of RP5-875H18.4--miRNA-218--SLIT2 may play a role in the occurrence of PAS.

Topics: Cesarean Section; Female; Gene Regulatory Networks; Humans; Intercellular Signaling Peptides and Proteins; MicroRNAs; Nerve Tissue Proteins; Placenta Accreta; Pregnancy; RNA, Long Noncoding; Signal Transduction; Transforming Growth Factor beta

This study aimed to evaluate whether trophoblastic transforming growth factor beta (TGF-β) and E-cadherin expression levels have a role in placenta percreta (PP) aetiopathogenesis.. This study was carried out in the Obstetrics & Gynecology and Pathology Departments of Harran University Medicine School. Forty-four women who underwent caesarean section for PP and other obstetric reasons were included in this study. PP was defined as the detection of placental invasion during the histopathological examination of the hysterectomy specimen, which passes the uterine wall as a whole layer and involves the uterine serosa. Placental tissue samples were collected from all pregnant patients to evaluate TGF-β and E-cadherin expression levels.. No significant difference was found in demographic features, including age, gestational week, number of pregnancies and body mass index, among the groups. Immunohistochemical staining against E-cadherin, a cell adhesion molecule, showed significantly reduced staining in PP patients (p = 0.048). TGF-β staining was also low in PP patients, but this difference was not significant (p = 0.107).. The findings of this study suggest that a decrease in trophoblastic E-cadherin expression may have an important role in PP aetiopathogenesis.

Topics: Adult; Cadherins; Female; Humans; Placenta Accreta; Pregnancy; Retrospective Studies; Transforming Growth Factor beta; Trophoblasts; Young Adult