{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:30:53Z","timestamp":1789083053739,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Heavy metals disrupt mitochondrial function and activate the NOD\u2010like receptor pyrin\u2010containing 3 (NLRP3) inflammasome. We investigated the effect of lead (Pb)\/cadmium (Cd) on mitochondrial function and NLRP3 inflammasome activation in human trophoblast under normoxic, hypoxic and pro\u2010inflammatory conditions. JEG\u20103, BeWo and HTR\u20108\/SVneo cells were exposed to Pb or Cd for 24\u00a0h in the absence or presence of hypoxia or pro\u2010inflammatory lipopolysaccharide (LPS) or poly(I:C). Then, we evaluated cell viability, apoptosis, mitochondrial DNA copy number (mtDNAcn), mitochondrial membrane potential (\u0394\u03a8), NLRP3 inflammasome proteins and interleukin (IL)\u20101\u03b2 secretion. Although our data showed that Pb, Cd, hypoxia, poly(I:C) and LPS decreased mtDNAcn in the three cell lines, the effects of these treatments on other biomarkers were different in the different cell lines. We found that hypoxia decreased \u0394\u03a8 and promoted apoptosis in JEG\u20103 cells, increased \u0394\u03a8 and prevented apoptosis in BeWo cells, and did not change \u0394\u03a8 and apoptosis in HTR\u20108\/SVneo cells. Moreover, Pb under hypoxic conditions reduced \u0394\u03a8 and promoted apoptosis of BeWo cells. Exposure of BeWo and HTR\u20108\/SVneo cells to hypoxia, Pb or Cd alone upregulated the expression of NLRP3 and pro\u2010caspase 1 but did not activate the NLRP3 inflammasome since cleaved\u2010caspase 1 and IL\u20101\u03b2 were not increased. To conclude, Pb and Cd affected trophoblast mitochondrial function and NLRP3 proteins in trophoblast cell lines, but in a cell line\u2010specific way.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16282-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The objective of this work was an understanding of the effect of lead (Pb) and cadmium (Cd) on mitochondrial function and NLRP3 inflammasome activation in human trophoblast cell lines under normoxic, hypoxic and pro\u2010inflammatory conditions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Apoptosis of JEG\u20103 cells was increased by hypoxia, while in BeWo cells, apoptosis was decreased by hypoxia, and in HTR\u20108\/SVneo, apoptosis was not affected by hypoxic treatment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Exposure to either Pb or Cd decreased mtDNAcn in three human placental trophoblast cell lines. However, Pb under hypoxia induced a decrease of \u0394\u03a8 and promoted apoptosis of BeWo cells, but Cd did not induce a reduction in \u0394\u03a8 in the three trophoblast cell lines under any conditions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Exposure to hypoxia, Pb or Cd increased NLRP3 and pro\u2010caspase 1 in BeWo and HTR\u20108\/SVneo cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our findings highlight that Pb and Cd affected trophoblast mitochondrial function and NLRP3 proteins in trophoblast cell lines but in a cell line\u2010specific way.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286755","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T15:33:30Z","timestamp":1724859210000},"page":"4225-4246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Differential effect of lead and cadmium on mitochondrial function and NLRP3 inflammasome activation in human trophoblast"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3507-7414","authenticated-orcid":false,"given":"Yifeng","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Pathology and Medical Biology University Medical Center Groningen and University of Groningen Groningen The Netherlands"},{"name":"Laboratory of Environmental Medicine and Developmental Toxicology Shantou University Medical College Shantou Guangdong China"},{"name":"Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care University Medical Centre Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijin","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Medicine and Developmental Toxicology Shantou University Medical College Shantou Guangdong China"},{"name":"Department of Cell Biology and Genetics Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Huo","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment Jinan University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost H. 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