Characterization of mitochondria in trophoblast cells derived from control and early-onset preeclamptic pregnancies via induced pluripotent stem cells

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ID: 327256
2026
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Abstract
Early embryonic development occurs in a low oxygen environment, and mitochondrial morphology and function are distinct in embryonic cells and pluripotent stem cells (PSC), which rely less on oxidative phosphorylation than differentiated cells. Oxidative phosphorylation increases with differentiation to trophoblast (TB) and this process is reversed by reprogramming of adult cells to pluripotency, but the influence of oxygen conditions on this process has not been characterized. When PSC were differentiated to trophoblast by treatment with BAP (BMP4, A83-01 and PD173074), cellular ATP concentrations increased equally in 5% and 20% oxygen conditions. Although oxygen conditions in culture altered transcripts encoding mitochondrial proteins, particularly by suppressing COX4l2 at 20% oxygen, there were no consistent differences in mitochondrial morphology in either cytotrophoblast (CTB) or syncytiotrophoblast (STB) cells with changing oxygen. These results suggest that TB adapt to maintain mitochondrial function at high and low oxygen during differentiation. In a previous study, iPSCs were derived from both control and early onset preeclampsia (EOPE) pregnancies and differentiated with BAP; high oxygen conditions impaired TB invasion only in cells from EOPE pregnancies. Here, the increase in ATP concentration with TB differentiation was less robust in EOPE cells, and cytochrome C and ATPase subunit transcripts differed between EOPE and control cells at high oxygen. However, investigation of mitochondrial morphology revealed no excess damage in EOPE-derived lines, and no difference in mitochondrial respiration was detected. Collectively, these data provide limited support for the hypothesis that intrinsic differences in mitochondria underlie poor TB invasion in EOPE.
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Authors Jessica Milano-Foster, Kameron Hahn, Juliann Leak, Grace Meers, Teka Khan, Megan A. Sheridan, R. Scott Rector, Danny J. Schust, Toshihiko Ezashi, R. Michael Roberts, Laura C. Schulz
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Journal biology of reproduction
Year 2026
DOI
10.1093/biolre/ioag182
URL
https://academic.oup.com/biolreprod/advance-article-pdf/doi/10.1093/biolre/ioag182/70868230/ioag182.pdf
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