title: Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.
abstract: Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans.
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory of Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: k.thiele@uke.de.
authors.forename: Kristin
authors.initials: K
authors.lastname: Thiele
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory of Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: M Emilia
authors.initials: ME
authors.lastname: Solano
authors.affiliation: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Kessler
authors.affiliation: Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roja
authors.initials: R
authors.lastname: Barikbin
authors.affiliation: Center for Diagnostics, Department of Clinical Chemistry/Central Laboratories, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Jung
authors.affiliation: Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Khalil
authors.initials: K
authors.lastname: Karimi
authors.affiliation: Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory of Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: p.arck@uke.de.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Arck
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000222:Adaptation, Physiological; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D000082:Acetaminophen