{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001310","ANALYSIS_ID":"AN002181","VERSION":"1","CREATED_ON":"January 30, 2020, 4:02 pm"},

"PROJECT":{"PROJECT_TITLE":"Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta–brain axis","PROJECT_SUMMARY":"Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to multinucleated giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, an inverse correlation existed between dopamine+ GCs and reductions spongiotrophoblast to GC area. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GC within the junctional zone. Third, imbalances in neurotransmitter-positive GC and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental–brain axis of the developing mouse fetus.","INSTITUTE":"University of Missouri","DEPARTMENT":"Life Sciences Center","LABORATORY":"Rosenfeld Lab","LAST_NAME":"Rosenfeld","FIRST_NAME":"Cheryl","ADDRESS":"Bond Life Sciences Center, 1201 Rollins St., Columbia, MO","EMAIL":"RosenfeldC@missouri.edu","PHONE":"573-882-5132","FUNDING_SOURCE":"NIEHS","PUBLICATIONS":"Mao et al, Proceedings National Academy of Science, USA,","CONTRIBUTORS":"Jiude Mao, Ashish Jain, Nancy D. Denslow, Mohammad-Zaman Nouri, Sixue Chen, Tingting Wang, Ning Zhu, Jin Koh, Saurav J. Sarma, Barbara W. Sumner, Zhentian Lei, Lloyd W. Sumner, Nathan J. Bivens, R. Michael Roberts, Geetu Tuteja, and Cheryl S. Rosenfeld"},

"STUDY":{"STUDY_TITLE":"C57 midgestation placental metabolomics analysis","STUDY_TYPE":"BPA, BPS exposure on placenta metabolite profile","STUDY_SUMMARY":"Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to multinucleated giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, an inverse correlation existed between dopamine+ GCs and reductions spongiotrophoblast to GC area. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GC within the junctional zone. Third, imbalances in neurotransmitter-positive GC and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental–brain axis of the developing mouse fetus.","INSTITUTE":"University of Missouri","DEPARTMENT":"Life Sciences Center","LABORATORY":"Univ. of Missouri Metabolomics Center","LAST_NAME":"Sumner","FIRST_NAME":"Lloyd","ADDRESS":"1201 Rollins Street Columbia, Missouri 65211-7310","EMAIL":"sumnerlw@missouri.edu","PHONE":"573-882-5486","NUM_GROUPS":"3 treatment X 2 sex = 6","TOTAL_SUBJECTS":"40","PUBLICATIONS":"Mao et al, Proceedings National Academy of Science, USA, 2020"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","GENOTYPE_STRAIN":"C57BL6J","AGE_OR_AGE_RANGE":"Embryonic day 12.5","GENDER":"Male and female","ANIMAL_ANIMAL_SUPPLIER":"Jackson Labs","ANIMAL_HOUSING":"polypropylene cages"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"3017-BPA-F",
"Factors":{"Exposure":"BPA","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3017-BPA-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3015-BPA-F",
"Factors":{"Exposure":"BPA","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3015-BPA-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2027-BPA-F",
"Factors":{"Exposure":"BPA","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2027-BPA-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2015-BPA-F",
"Factors":{"Exposure":"BPA","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2015-BPA-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2021-BPA-F",
"Factors":{"Exposure":"BPA","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2021-BPA-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3018-BPA-F",
"Factors":{"Exposure":"BPA","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3018-BPA-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3017-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3017-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"3015-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3015-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2027-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2027-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2009-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2009-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"3018-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3018-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2015-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2015-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2021-BPA-M",
"Factors":{"Exposure":"BPA","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2021-BPA-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2013-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2013-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2025-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2025-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2001-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2001-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3004-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3004-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2019-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2019-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2007-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2007-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2009-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2009-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3002-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3002-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2031-BPS-F",
"Factors":{"Exposure":"BPS","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2031-BPS-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2025-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2025-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2001-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2001-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"3004-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3004-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2019-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2019-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2013-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2013-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"3002-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3002-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2007-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2007-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2031-BPS-M",
"Factors":{"Exposure":"BPS","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2031-BPS-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2029-Control-F",
"Factors":{"Exposure":"CTRL","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2029-Control-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2005-Control-F",
"Factors":{"Exposure":"CTRL","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2005-Control-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3009-Control-F",
"Factors":{"Exposure":"CTRL","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3009-Control-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3008-Control-F",
"Factors":{"Exposure":"CTRL","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"3008-Control-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"2017-Control-F",
"Factors":{"Exposure":"CTRL","Gender":"female"},
"Additional sample data":{"RAW_FILE_NAME":"2017-Control-F.D"}
},
{
"Subject ID":"-",
"Sample ID":"3009-Control-M",
"Factors":{"Exposure":"CTRL","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3009-Control-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2005-Control-M",
"Factors":{"Exposure":"CTRL","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2005-Control-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2029-Control-M",
"Factors":{"Exposure":"CTRL","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2029-Control-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"3008-Control-M",
"Factors":{"Exposure":"CTRL","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"3008-Control-M.D"}
},
{
"Subject ID":"-",
"Sample ID":"2017-Control-M",
"Factors":{"Exposure":"CTRL","Gender":"male"},
"Additional sample data":{"RAW_FILE_NAME":"2017-Control-M.D"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"e12.5 placenta samples were collected immediately after dams were euthanized","SAMPLE_TYPE":"Placenta","COLLECTION_METHOD":"snap freezen in LN2 right after placenta was isolated","COLLECTION_LOCATION":"Univ. of Missouri Animal Science Research Center","COLLECTION_FREQUENCY":"1 time from each animal","VOLUMEORAMOUNT_COLLECTED":"50 mg","STORAGE_VIALS":"1.5 ml vials"},

"TREATMENT":{"TREATMENT_SUMMARY":"2 weeks before breeding and during gestation, dams were fed BPA, or BPS, or vehicle till tissue collection at 12.5 DPC","TREATMENT_ROUTE":"oral","TREATMENT_DOSE":"200 microg/kg body weight","TREATMENT_VEHICLE":"70% ethanol dry out onto Nabisco Nilla wafer","ANIMAL_ENDP_EUTHANASIA":"yes","TREATMENT_COMPOUND":"Bisphenol A, bisphenol S"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Freshly isolated mouse placneta tissue was snap frozen in liqud nitrogen and no further preparation. Samples were storred at -52C in lyophilyzer and -20C after weighing. Extracts were dried under nitrogen flow and stored at -20C","PROCESSING_METHOD":"Frozen tissues were lyophilized for 24 hrs before weighing.","PROCESSING_STORAGE_CONDITIONS":"Described in summary","EXTRACTION_METHOD":"samples were extracted water, containing 25 μg/ml ribitol, vortex for 20 seconds, sonicated for 15 minutes, incubated at 50C for 1h","EXTRACT_ENRICHMENT":"Sample tubes were sonicated for 15 minutes at 13000g then collected the supernatantant","EXTRACT_STORAGE":"-20℃","SAMPLE_RESUSPENSION":"Sample was resuspended in 25 μl of pyridine containing 15 mg/ml methoxyamine hydrochloride","SAMPLE_DERIVATIZATION":"Sample was derivatized with 25 μl MSTFA (N-methyl-N-(trimethyl-silyl)trifluoroacetamide) + 1% TMCS (chlorotrimethylsilane)","SAMPLE_SPIKING":"Ribitol was used in the extraction solvent as an internal standard"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"GC","INSTRUMENT_NAME":"Agilent 6890N;Agilent 5973N","COLUMN_NAME":"DB-5MS (J&W Scientific)","FLOW_RATE":"1mL/Min of Helium gas","COLUMN_TEMPERATURE":"80 C for 2 min, then ramped at 5 C /min to 315 C and held at 315 C for 12 min","INJECTION_TEMPERATURE":"280 C","INTERNAL_STANDARD":"Ribitol","SAMPLE_INJECTION":"split injection (split ration 5:1) with 1uL injection volume","CHROMATOGRAPHY_COMMENTS":"Agilent 6890N coupled to an Agilent 5973N"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS","DETECTOR_TYPE":"electron multiplier"},

"MS":{"INSTRUMENT_NAME":"Agilent 5973","INSTRUMENT_TYPE":"Single quadrupole","MS_TYPE":"EI","ION_MODE":"POSITIVE","MS_COMMENTS":"70 eV electron ionization","ION_SOURCE_TEMPERATURE":"230 C","MASS_ACCURACY":"0.1 m/z","DATAFORMAT":".D","SCAN_RANGE_MOVERZ":"50 to 650 m/z","MS_RESULTS_FILE":"ST001310_AN002181_Results.txt UNITS:relative instrument response Has m/z:Yes Has RT:Yes RT units:Minutes"}

}