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An integral role of mitochondrial function in the pathophysiology of preeclampsia

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Abstract

Preeclampsia (PE) is associated with high maternal and perinatal morbidity and mortality. The development of effective treatment strategies remains a major challenge due to the limited understanding of the pathogenesis. In this review, we summarize the current understanding of PE research, focusing on the molecular basis of mitochondrial function in normal and PE placentas, and discuss perspectives on future research directions. Mitochondria integrate numerous physiological processes such as energy production, cellular redox homeostasis, mitochondrial dynamics, and mitophagy, a selective autophagic clearance of damaged or dysfunctional mitochondria. Normal placental mitochondria have evolved innovative survival strategies to cope with uncertain environments (e.g., hypoxia and nutrient starvation). Cytotrophoblasts, extravillous trophoblast cells, and syncytiotrophoblasts all have distinct mitochondrial morphology and function. Recent advances in molecular studies on the spatial and temporal changes in normal mitochondrial function are providing valuable insight into PE pathogenesis. In PE placentas, hypoxia-mediated mitochondrial fission may induce activation of mitophagy machinery, leading to increased mitochondrial fragmentation and placental tissue damage over time. Repair mechanisms in mitochondrial function restore placental function, but disruption of compensatory mechanisms can induce apoptotic death of trophoblast cells. Additionally, molecular markers associated with repair or compensatory mechanisms that may influence the development and progression of PE are beginning to be identified. However, contradictory results have been obtained regarding some of the molecules that control mitochondrial biogenesis, dynamics, and mitophagy in PE placentas. In conclusion, understanding how the mitochondrial morphology and function influence cell fate decisions of trophoblast cells is an important issue in normal as well as pathological placentation biology. Research focusing on mitochondrial function will become increasingly important for elucidating the pathogenesis and effective treatment strategies of PE.

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Acknowledgements

Figures were created by Toyomi Kobayashi (Ms.Clinic MayOne, Nara, Japan; https://www.mscl-mayone.com/; accessed on 9 October 31, 2023).

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Authors and Affiliations

  1. Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara, 634-0813, Japan

    Hiroshi Kobayashi & Shogo Imanaka

  2. Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan

    Hiroshi Kobayashi, Chiharu Yoshimoto, Sho Matsubara, Hiroshi Shigetomi & Shogo Imanaka

  3. Department of Obstetrics and Gynecology, Nara Prefecture General Medical Center, 2-897-5 Shichijyonishi-machi, Nara, 630-8581, Japan

    Chiharu Yoshimoto

  4. Department of Medicine, Kei Oushin Clinic, 5-2-6, Naruo-cho, Nishinomiya, 663-8184, Japan

    Sho Matsubara

  5. Department of Gynecology and Reproductive Medicine, Aska Ladies Clinic, 3-3-17 Kitatomigaoka-cho, Nara, 634- 0001, Japan

    Hiroshi Shigetomi

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  1. Hiroshi Kobayashi
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Contributions

Conception and design, H.K. Acquisition of data, S.M., C.Y., and S.I. Analysis and Interpretation of data, H.S. Drafting of the manuscript, H.K. Critical revision of the manuscript for important intellectual content, S.M., C.Y., H.S., and S.I. Statistical analysis, H.S. Administrative technical or material support, H.K. Supervision, S.I. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Hiroshi Kobayashi.

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Kobayashi, H., Yoshimoto, C., Matsubara, S. et al. An integral role of mitochondrial function in the pathophysiology of preeclampsia. Mol Biol Rep 51, 330 (2024). https://doi.org/10.1007/s11033-024-09285-z

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