title: Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.
abstract: Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kassotis
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Kara C
authors.initials: KC
authors.lastname: Klemp
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Danh C
authors.initials: DC
authors.lastname: Vu
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Meng
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Besch-Williford
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pinatti
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Zoeller
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Erma Z
authors.initials: EZ
authors.lastname: Drobnis
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Victoria D
authors.initials: VD
authors.lastname: Balise
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Chiamaka J
authors.initials: CJ
authors.lastname: Isiguzo
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Williams
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Tillitt
authors.affiliation: Nicholas School of the Environment (C.D.K.), Duke University, Durham, North Carolina 27708; Department of Obstetrics, Gynecology, and Women's Health (K.C.K., C.-X.M., E.Z.D., V.D.B., C.J.I., S.C.N.), Department of Forestry (D.C.V., C.-H.L.), Division of Biological Sciences (V.D.B., M.A.W., S.C.N.), University of Missouri, Columbia, Missouri 65211; IDEXX RADIL Pathology Services (C.L.B.-W.), Columbia, Missouri 65201; Department of Biology (L.P., R.T.Z.), University of Massachusetts Amherst, Amherst, Massachusetts 01003; and US Geological Survey (D.E.T.), Columbia Environmental Research Center, Columbia, Missouri 65201.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nagel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D000067071:Hydraulic Fracking; D008297:Male; D051379:Mice; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011944:Receptors, Androgen / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000187:drug effects; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D062065:Wastewater / Q000737:chemistry*
chemical_list: D052244:Endocrine Disruptors; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011988:Receptors, Thyroid Hormone; D013739:Testosterone; D062065:Wastewater