AT-rich interactive domain 1A protein expression in normal and pathological pregnancies complicated by preeclampsia

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AT‑rich interactive domain 1A protein expression in normal and pathological pregnancies complicated by preeclampsia Sonia Fantone1 · Roberta Mazzucchelli2 · Stefano Raffaele Giannubilo3 · Andrea Ciavattini3 · Daniela Marzioni1   · Giovanni Tossetta1,3 Accepted: 4 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract AT-rich interactive domain 1A (ARID1A, as known as BAF250a) is a subunit of human switch/sucrose nonfermentable chromatin remodeling complex with tumour suppressor function. Mutations of Arid1a have been reported in many human cancers and low expression of this protein has been correlated to a poor prognosis outcome in patients affected by some types of cancer. Although there are many studies regarding ARID1A functions in cancer, little is known about its role in regulating cell differentiation and normal tissues homeostasis. Here, we investigate ARID1A expression in normal placental tissues of first and third trimester of gestation and in pathological placental tissues of pregnancy complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) to evaluate a possible role of this protein in trophoblast differentiation. We found that ARID1A was specifically expressed in villous and extravillous cytotrophoblastic cells in normal placentas whereas syncytiotrophoblast was negative. Interestingly, ARID1A was expressed in both cytotrophoblastic cells and syncytiotrophoblast in placentas affected by PE and PE-IUGR. Moreover, ARID1A was also present in syncitial knots of pathological placentas. The present results indicate that ARID1A is a good marker of poor trophoblast differentiation in these pathologies, because the significant high positive staining in syncytiotrophoblast nuclei may suggest a poor differentiation of this trophoblast layer due to the cytotrophoblast cells fusion with the syncytiotrophoblast overlaying before arresting their cell cycle. Keywords  ARID1A · Placenta · Preeclampsia · IUGR​ · Pregnancy · Thophoblast

Introduction The placenta is an essential organ for normal in utero development in humans and mammals in general, playing different and essential functions during normal pregnancy (Costa 2016). Its multifaceted role has been demonstrated Daniela Marzioni and Giovanni Tossetta contributed equally to this work. * Daniela Marzioni [email protected] 1



Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy

2



Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, United Hospitals, Ancona, Italy

3

Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Università Politecnica delle Marche, Salesi Hospital, Azienda Ospedaliero Universitaria, Ancona, Italy



in different way by studying human pregnancy in normal and pathological conditions (Booker and Moroz 2019; Gurugubelli Krishna and Vishnu Bhat 2018; Phipps et al. 2019) and using animal models, although the placenta varies from sp