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PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration.

ABSTRACT: Proper differentiation of trophoblast cells in the human placenta is a prerequisite for a successful pregnancy, and dysregulation of this process may lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific markers for different types of trophoblast cells is essential for understanding trophoblast differentiation. Here, we report that placenta-specific protein 8 (PLAC8) is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal interface. Using model systems, including placental villi-decidua co-culture, iEVTs induction by using primary trophoblast cells or explants, etc., we found that PLAC8 promotes invasion and migration of iEVTs. Mechanistically, time-lapse imaging, GTPase activity assay, co-immunoprecipitation and RNA-seq studies show that PLAC8 increases the Cdc42 and Rac1 activities, and further induces the formation of filopodia at the leading edge of the migratory trophoblast cells. More interestingly, PLAC8 is significantly upregulated under hypoxia and expression of PLAC8 is higher in iEVTs from preeclamptic placentas when compared with those from the normal control placentas. Together, PLAC8 is a new marker for iEVTs and plays an important role in promoting trophoblast invasion and migration.

SUBMITTER: Chang WL

PROVIDER: S-EPMC5825838 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration.

Chang Wen-Lin WL Liu Ya-Wei YW Dang Yan-Li YL Jiang Xiang-Xiang XX Xu Honglin H Huang Xing X Wang Yan-Ling YL Wang Haibin H Zhu Cheng C Xue Li-Qun LQ Lin Hai-Yan HY Meng Wenxiang W Wang Hongmei H

Development (Cambridge, England) 20180129 2

Proper differentiation of trophoblast cells in the human placenta is a prerequisite for a successful pregnancy, and dysregulation of this process may lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific markers for different types of trophoblast cells is essential for understanding trophoblast differentiation. Here, we report that placenta-specific protein 8 (PLAC8) is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal in ...[more]

PMID: 29361555

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Project description:BackgroundSERPINE2, one of the potent serpins belonging to the plasminogen activator (PA) system, is involved in the tissue remodeling. We previously demonstrated the expression patterns of Serpine2 in the mouse placenta and uterus, indicating that Serpine2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. In this study, we further investigated the expression pattern of SERPINE2 in the human placenta and explored possible functional roles of SERPINE2 in regulating trophoblast activity.MethodsPlacental tissues from various trimesters were collected for real-time reverse-transcription polymerase chain reaction quantification. Immunohistochemical staining was performed in placental tissues to assure localization of SERPINE2. SERPINE2 small interfering (si) RNA was applied to suppress its expression in villous explants and extravillous trophoblast-like 3A cells. Subsequent experiments to evaluate SERPINE2 levels, villous outgrowth, trophoblast invasion, and tube formation were performed.ResultsSERPINE2 messenger RNA was detected in the human placenta during pregnancy with the highest levels in the third trimester. The SERPINE2 protein was present in villous syncytiotrophoblasts and trophoblasts of chorionic villi for anti-SERPINE2 immunostaining. Extravillous trophoblasts in the chorionic plate and basal plate confronting the invasive face of anchoring villi were also positive. In most decidual cells, SERPINE2 was observed in the cytoplasm. In addition, fibrinoid deposit was weakly immunoreactive. Introduction of SERPINE2 siRNA into villous explants and trophoblast cells led to significantly reduced villous outgrowth, and trophoblastic migration and invasion. Moreover, capillary-like network formation of 3A cells in Matrigel was greatly attenuated by SERPINE2 siRNA and SERPINE2 antiserum.ConclusionsThese data identify the temporal and spatial SERPINE2 distribution in the human placenta and suggest its possible role in modulating tissue remodeling of extravillous trophoblasts in the placenta during pregnancy.

Project description:IntroductionThe increasing cesarean section rate has led to an increase in the number of subsequent pregnancies resulting in a cesarean scar pregnancy. There appears to be preferential attachment of the blastocyst to the scar site, which may be associated with defective decidua in that region, resulting in abnormal implantation, which can in turn negatively affect the success of the pregnancy. The aim of the current study was to evaluate the extravillous trophoblast, decidua, and myometrium in scar and adjacent non-scar regions of the implantation site of a cesarean scar pregnancy.Material and methodsSamples containing a gestational mass were obtained by laparoscopic excision from patients with a cesarean scar pregnancy at 6-11 weeks of gestation as diagnosed by transvaginal or transabdominal ultrasound (n = 8 type II cesarean scar pregnancy). Cesarean scar pregnancy tissues were separated into scar and non-scar regions, and the scar regions were sub-separated into non-implantation and implantation sites. Serial sections were histologically examined after hematoxylin and eosin, Masson's trichrome and immunochemical staining, and changes in the myometrium, extravillous trophoblast, and decidua were evaluated.ResultsIn cesarean scar pregnancy, compared with scars not in the implantation site, scars in the implantation site displayed increased fibrosis, and had disrupted myometrium, which was related to varying patterns of E-cadherin expression as a response to extravillous trophoblast invasion. In addition, local decidua was found at the non-scar implantation sites, with multinucleated trophoblast giant cell accumulation and shallow invasion. These features were not evident in the scar implantation sites.ConclusionsThis study emphasizes that the decidua drives multinucleated trophoblast giant cell differentiation, limiting the degree of invasion. Better characterization of this differentiation process may be helpful for better management and avoidance of the consequences of cesarean scar pregnancy.

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PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration.

Publications

PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration.

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