Perfluorooctanoic acid (PFOA) inhibits steroidogenesis and mitochondrial function in bovine granulosa cells in vitro

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dc.authoridPlewes, Michele/0000-0002-6086-0104
dc.authoridClark, Kendra/0000-0001-8843-7917
dc.authoridKabakci, Ruhi/0000-0001-9131-0933
dc.authoridDavis, John S/0000-0003-3468-4079
dc.contributor.authorKabakci, Ruhi
dc.contributor.authorClark, Kendra L.
dc.contributor.authorPlewes, Michele R.
dc.contributor.authorMonaco, Corrine F.
dc.contributor.authorDavis, John S.
dc.date.accessioned2025-01-21T16:43:21Z
dc.date.available2025-01-21T16:43:21Z
dc.date.issued2023
dc.departmentKırıkkale Üniversitesi
dc.description.abstractPerfluorooctanoic acid (PFOA) is a persistent environmental contaminant. Due to the ubiquitous presence of PFOA in the environment, the impacts of PFOA exposure not only affect human reproductive health but may also affect livestock reproductive health. The focus of this study was to determine the effects of PFOA on the phys-iological functions of bovine granulosa cells in vitro. Primary bovine granulosa cells were exposed to 0, 4, and 40 mu M PFOA for 48 and 96 h followed by analysis of granulosa cell function including cell viability, steroidogenesis, and mitochondrial activity. Results revealed that PFOA inhibited steroid hormone secretion and altered the expression of key enzymes required for steroidogenesis. Gene expression analysis revealed decreases in mRNA transcripts for CYP11A1 , HSD3B , and CYP19A1 and an increase in STAR expression after PFOA exposure. Similarly, PFOA decreased levels of CYP11A1 and CYP19A1 protein. PFOA did not impact live cell number, alter the cell cycle, or induce apoptosis, although it reduced metabolic activity, indicative of mitochondrial dysfunction. We observed that PFOA treatment caused a loss of mitochondrial membrane potential and increases in PINK protein expression, suggestive of mitophagy and mitochondrial damage. Further analysis revealed that these changes were associated with increased levels of reactive oxygen species. Expression of autophagy related proteins phosphoULK1 and LAMP2 were increased after PFOA exposure, in addition to an increased abundance of lysosomes, characteristic of increased autophagy. Taken together, these findings suggest that PFOA can negatively impact granulosa cell steroidogenesis via mitochondrial dysfunction.
dc.description.sponsorshipScientific and Technological Research Council of Turkey [TUBITAK-1059B192001213]; NIH [P01AG029531]; Olson Center for Women 's Health; VA Senior Research Career Scientist Award [IK6BX005797]; Nebraska Research Initiative (NRI); Fred and Pamela Buffett Cancer Center 's National Cancer Institute Cancer Support Grant; Office of the Vice Chancellor for Research; Nebraska Banker 's Fund; NIH-NCRR Shared Instrument Program; VA; AHA; University of Nebraska Foundation; [F32HD106722]; [IK2BX004911]; [I01BX004272]; [23PRE1018741]
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey, TUBITAK-1059B192001213 (RK) , NIH F32HD106722 (KLC) , VA IK2BX004911 (MRP) , AHA 23PRE1018741 (CFM) , VA I01BX004272 (JSD) , NIH P01AG029531 (JSD) and the Olson Center for Women 's Health (JSD) . JSD is the recipient of a VA Senior Research Career Scientist Award (IK6BX005797) . We acknowledge use of the University of Nebraska Medical Center-UNMC Advanced Microscopy Core Facility, RRID:SCR_022467, P20 GM 10 3427, P30 GM 10 6397, and P30 CA036727 . The UNMC Flow Cytometry Research Facility is administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center 's National Cancer Institute Cancer Support Grant. Major instrumentation has been provided by the Office of the Vice Chancellor for Research, The University of Nebraska Foundation, the Nebraska Banker 's Fund, and by the NIH-NCRR Shared Instrument Program.
dc.identifier.doi10.1016/j.envpol.2023.122698
dc.identifier.issn0269-7491
dc.identifier.issn1873-6424
dc.identifier.pmid37832777
dc.identifier.scopus2-s2.0-85173862712
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.envpol.2023.122698
dc.identifier.urihttps://hdl.handle.net/20.500.12587/25250
dc.identifier.volume338
dc.identifier.wosWOS:001098077700001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Sci Ltd
dc.relation.ispartofEnvironmental Pollution
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241229
dc.subjectPerfluorooctanoic acid; bovine; granulosa cells; steroidogenesis; mitochondria; autophagy
dc.titlePerfluorooctanoic acid (PFOA) inhibits steroidogenesis and mitochondrial function in bovine granulosa cells in vitro
dc.typeArticle

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