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Reversible EMT and MET mediate amnion remodeling during pregnancy and labor.

ABSTRACT: The amnion is remodeled during pregnancy to protect the growing fetus it contains, and it is particularly dynamic just before and during labor. By combining ultrastructural, immunohistochemical, and Western blotting analyses, we found that human and mouse amnion membranes during labor were subject to epithelial-to-mesenchymal transition (EMT), mediated, in part, by the p38 mitogen-activated protein kinase (MAPK) pathway responding to oxidative stress. Primary human amnion epithelial cell cultures established from amnion membranes from nonlaboring, cesarean section deliveries exhibited EMT after exposure to oxidative stress, and the pregnancy maintenance hormone progesterone (P4) reversed this process. Oxidative stress or transforming growth factor-? (TGF-?) stimulated EMT in a manner that depended on TGF-?-activated kinase 1 binding protein 1 (TAB1) and p38 MAPK. P4 stimulated the reverse transition, MET, in primary human amnion mesenchymal cells (AMCs) through progesterone receptor membrane component 2 (PGRMC2) and c-MYC. Our results indicate that amnion membrane cells dynamically transition between epithelial and mesenchymal states to maintain amnion integrity and repair membrane damage, as well as in response to inflammation and mechanical damage to protect the fetus until parturition. An irreversible EMT and the accumulation of AMCs characterize the amnion membranes at parturition.

SUBMITTER: Richardson LS

PROVIDER: S-EPMC7092701 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Reversible EMT and MET mediate amnion remodeling during pregnancy and labor.

Richardson Lauren S LS Taylor Robert N RN Menon Ramkumar R

Science signaling 20200211 618

The amnion is remodeled during pregnancy to protect the growing fetus it contains, and it is particularly dynamic just before and during labor. By combining ultrastructural, immunohistochemical, and Western blotting analyses, we found that human and mouse amnion membranes during labor were subject to epithelial-to-mesenchymal transition (EMT), mediated, in part, by the p38 mitogen-activated protein kinase (MAPK) pathway responding to oxidative stress. Primary human amnion epithelial cell culture ...[more]

PMID: 32047115

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Project description:BACKGROUND:The correct dating of pregnancy is critical to support timely decisions and provide obstetric care during birth. The early obstetric ultrasound assessment before 14 weeks is considered the best reference to assist in determining gestational age (GA), with an accuracy of ±5 to 7 days. However, this information is limited in many settings worldwide. OBJECTIVE:The aim of this study is to analyze the association between the obstetric interventions during childbirth and the quality of GA determination, according to the first antenatal ultrasound assessment, which assisted the calculation. METHODS:This is a hospital-based cohort study using medical record data of 2113 births at a perinatal referral center. The database was separated into groups and subgroups of analyses based on the reference used by obstetricians to obtain GA at birth. Maternal and neonatal characteristics, mode of delivery, oxytocin augmentation, and forceps delivery were compared between groups of pregnancies with GA determination at different reference points: obstetric ultrasound assessment 14 weeks, 20 weeks, and ?20 weeks or without antenatal ultrasound (suboptimal dating). Ultrasound-based GA information was associated with outcomes between the interest groups using chi-square tests, odds ratios (OR) with 95% CI, or the Mann-Whitney statistical analysis. RESULTS:The chance of nonspontaneous delivery was higher in pregnancies with 14 weeks ultrasound-based GA (OR 1.64, 95% CI 1.35-1.98) and 20 weeks ultrasound-based GA (OR 1.58, 95% CI 1.31-1.90) when compared to the pregnancies with ?20 weeks ultrasound-based GA or without any antenatal ultrasound. The use of oxytocin for labor augmentation was higher for 14 weeks and 20 weeks ultrasound-based GA, OR 1.41 (95% CI 1.09-1.82) and OR 1.34 (95% CI 1.04-1.72), respectively, when compared to those suboptimally dated. Moreover, maternal blood transfusion after birth was more frequent in births with suboptimal ultrasound-based GA determination (20/657, 3.04%) than in the other groups (14 weeks ultrasound-based GA: 17/1163, 1.46%, P=.02; 20 weeks ultrasound-based GA: 25/1456, 1.71%, P=.048). Cesarean section rates between the suboptimal dating group (244/657, 37.13%) and the other groups (14 weeks: 475/1163, 40.84%, P=.12; 20 weeks: 584/1456, 40.10%, P=.20) were similar. In addition, forceps delivery rates between the suboptimal dating group (17/657, 2.6%) and the other groups (14 weeks: 42/1163, 3.61%, P=.24; 20 weeks: 46/1456, 3.16%, P=.47) were similar. Neonatal intensive care unit admission was more frequent in newborns with suboptimal dating (103/570, 18.07%) when compared with the other groups (14 weeks: 133/1004, 13.25%, P=.01; 20 weeks: 168/1263, 13.30%, P=.01), excluding stillbirths and major fetal malformations. CONCLUSIONS:The present analysis highlighted relevant points of health care to improve obstetric assistance, confirming the importance of early access to technologies for pregnancy dating as an essential component of quality antenatal care.

Project description:BackgroundThe epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) play pivotal roles in metastasis of epithelial cancers. The distinction between them has shed new light on the molecular mechanisms of tumor metastasis. Recently, tumor microenvironment (TM) has been identified as one of the most potent inducers of EMT and MET. TM is characterized by its complexity and flexibility. The purpose of this study was to ascertain the exact effect of each distinct TM component on the evolution hepatocellular carcinoma (HCC) metastasis.MethodsTwo different cell culture models were used. The HCC cell line Bel-7402 was co-cultured with the normal liver cell line HL-7702 or with the retinal vascular endothelial cell line RF/6A in double-layer six-well plates, imitating the direct interaction between tumor-host cells and tumor cells. Bel-7402 was also cultured in the conditioned medium (CM) of the human lung fibroblast cell line MRC-5, HL-7702 or RF/6A, imitating an indirect interaction. Integrin ?1, ?3, ?4, ?7, laminin ?3, E-cadherin and Snail levels were measured by quantitative RT-PCR in tumor sepecimens from 42 resected HCC.ResultsWe found that Bel-7402 cells co-cultured with HL-7702 or RF/6A cells were induced to undergo MET. The expression of E-cadherin, ?-catenin and ?-catenin was up-regulated, accompanied with a strengthened E-cadherin/catenin complex on the membrane of co-cultured Bel-7402 cells. Consequently, the invasion and migration ability of cells was declined. Conversely, Bel-7402 cells cultured in conditioned medium from MRC-5 cells underwent an EMT-like transformation as the cells became elongated with increased invasion and migration ability. Furthermore, we demonstrated that HL-7702 cells could generally inhibit the tumorigenicity and viability of Bel-7402 cells. We also found that integrin ?1 expression was negatively associated with capsular formation, and that integrin ?4 expression was negatively associated with CK19 expression.ConclusionOur findings highlight the strong influences exerted by TM on tumor progression through EMT and MET by impacting the expression of adhesion molecules, including the E-cadherin/catenin complex, laminins and integrins.

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Reversible EMT and MET mediate amnion remodeling during pregnancy and labor.

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Reversible EMT and MET mediate amnion remodeling during pregnancy and labor.

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