title: Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions.
abstract: The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant.
authors.affiliation: INSERM, U1139, Paris, France; Université Paris Descartes, Paris, France; Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry Cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pidoux
authors.affiliation: INSERM, U1139, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gerbaud
authors.affiliation: INSERM, U1139, Paris, France; Université Paris Descartes, Paris, France; PremUp, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Guibourdenche
authors.affiliation: Université Paris Sud, EA4529, UFR de Pharmacie, Châtenay-Malabry Cedex, France; APHP, Hôpital de Bicêtre, Service de biochimie, 94275 Le Kremlin Bicêtre, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Thérond
authors.affiliation: INSERM, U1139, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ferreira
authors.affiliation: PremUp, Paris, France; Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry Cedex, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Simasotchi
authors.affiliation: INSERM, U1139, Paris, France; Université Paris Descartes, Paris, France; PremUp, Paris, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Evain-Brion
authors.affiliation: INSERM, U1139, Paris, France; Université Paris Descartes, Paris, France; PremUp, Paris, France; Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gil
mesh_terms: D000328:Adult; D026962:Amino Acid Transport System ASC / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D008431:Maternal-Fetal Exchange; D015778:Minor Histocompatibility Antigens; D018384:Oxidative Stress; D021041:Placental Circulation; D010926:Placental Hormones / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D026962:Amino Acid Transport System ASC; D015778:Minor Histocompatibility Antigens; D010926:Placental Hormones; C420506:SLC1A5 protein, human; D005557:Formaldehyde