title: Potential involvement of placental AhR in unexplained recurrent spontaneous abortion.
abstract: Recurrent spontaneous abortion (RSA) is a common complication of pregnancy. Recent studies have demonstrated that the aryl hydrocarbon receptor (AhR) might play important roles in establishing and maintaining early pregnancy. In this study, we found that placental AhR protein levels were significantly lower and placental CYP1A1 mRNA levels were higher in unexplained RSA (URSA) patients than in control subjects. The results of immunohistochemical analyzes showed that placental AhR was expressed in syncytiotrophoblast cells and that the level of AhR was markedly lower in these cells in URSA subjects than in control subjects. β-Naphthoflavone (β-NF, an AhR ligand) at 5μM significantly inhibited proliferation and migration in HTR-8/SVneo cells and was associated with the activation of AhR. Moreover, overexpressing AhR in JAR cells significantly increased CYP1A1 mRNA levels and inhibited cell migration. These results indicate that AhR is highly activated in URSA placentas and that the activation of AhR in the placenta might impair trophoblast cell proliferation and migration, possibly leading to the occurrence of URSA.
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China.
authors.forename: X
authors.initials: X
authors.lastname: Chang
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China.
authors.forename: S
authors.initials: S
authors.lastname: Bao
authors.affiliation: Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Ob./Gyn., University of Wisconsin-Madison, Madison, WI 53715 USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ob./Gyn., University of Wisconsin-Madison, Madison, WI 53715 USA.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China; Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China. Electronic address: tduan@yahoo.com.
authors.forename: T
authors.initials: T
authors.lastname: Duan
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040 PR China. Electronic address: kaiwangcn@yahoo.com.
authors.forename: K
authors.initials: K
authors.lastname: Wang
mesh_terms: D000026:Abortion, Habitual / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D019363:Cytochrome P-450 CYP1A1; D007211:Indoles; D018336:Receptors, Aryl Hydrocarbon; D013844:Thiazoles; D019324:beta-Naphthoflavone; C548651:2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester; C111235:AHR protein, human; C569463:CYP1A1 protein, human
keywords: Aryl hydrocarbon receptor; Migration; Placenta; Proliferation; Trophoblast cells; Unexplained recurrent spontaneous abortion