title: Adverse Reproductive and Developmental Health Outcomes Following Prenatal Exposure to a Hydraulic Fracturing Chemical Mixture in Female C57Bl/6 Mice.
abstract: Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 μg/kg·d, flutamide at 50 mg/kg·d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies.
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Christopher D
authors: CD
authors: Kassotis
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: John J
authors: JJ
authors: Bromfield
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Kara C
authors: KC
authors: Klemp
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Chun-Xia
authors: CX
authors: Meng
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Andrew
authors: A
authors: Wolfe
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: R Thomas
authors: RT
authors: Zoeller
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Victoria D
authors: VD
authors: Balise
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Chiamaka J
authors: CJ
authors: Isiguzo
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Donald E
authors: DE
authors: Tillitt
authors: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Animal Sciences (J.J.B.) and D. H. Barron Reproductive and Perinatal Biology Research Program (J.J.B.), University of Florida, Gainesville, Florida 32611; Department of Obstetrics, Gynecology and Women's Health (K.C.K., C.-X.M.,V.D.B., C.J.I., S.C.N.) and Division of Biological Sciences (V.D.B., S.C.N.), University of Missouri, Columbia, Missouri 65211; Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Biology (RTZ), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and United States Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors: Susan C
authors: SC
authors: Nagel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D000067071:Hydraulic Fracking; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D010907:Pituitary Hormones / Q000097:blood*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*; D012741:Sexual Maturation / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors; D010907:Pituitary Hormones