Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment
Background Insufficient nutrition during pregnancy can lead to negative health outcomes for both mother and foetus. Maternal undernourishment (MUN) can be due to many factors like hyperemesis gravidarum or poor access to nutrition. Just as MUN can affect the mother and foetus, it can adversely affec...
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Obstetrics and Gynaecology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/01443615.2025.2460545 |
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| author | Mia Camilliere Marella R. Verde Michael S. Wolin May M. Rabadi Brian B. Ratliff |
| author_facet | Mia Camilliere Marella R. Verde Michael S. Wolin May M. Rabadi Brian B. Ratliff |
| author_sort | Mia Camilliere |
| collection | DOAJ |
| description | Background Insufficient nutrition during pregnancy can lead to negative health outcomes for both mother and foetus. Maternal undernourishment (MUN) can be due to many factors like hyperemesis gravidarum or poor access to nutrition. Just as MUN can affect the mother and foetus, it can adversely affect the vital placental interface between the two. We suspect an observed increase in fetuin-B and oxidative stress in MUN placentas could be major players responsible for the placental insufficiency often seen with MUN.Methods To establish a model of MUN during pregnancy, a reduced protein chow was fed to pregnant dams at a caloric deficit. We examined the MUN placentas and the downstream effects of fetuin-B and oxidative stress at the whole organ and trophoblast levels. We examined fetuin-B’s role in trophoblast pathology by measuring apoptosis, proliferation, TLR4 activation, expression of NF-ΚB p65, oxidative stress, and mitochondrial superoxide production. The effects of MUN and fetuin-B on mitochondrial superoxide production, antioxidant levels, metabolism, and electron transport chain complex activity were compared directly. Pharmaceutical interventions were utilised to narrow down specific pathways involved.Results Studies indicated that MUN and oxidative stress upregulated fetuin-B in the placenta. This relationship displayed a positive feedback loop as fetuin-B, in turn, promoted oxidative stress through activation of TLR4. Consequently, MUN, fetuin-B, and oxidative stress promoted apoptosis and reduced proliferative expansion of trophoblast, thereby reducing their quantity. MUN and fetuin-B reduced mitochondrial metabolism and function, promoting mitochondrial dysregulation and superoxide generation in MUN trophoblasts.Conclusions Our study sheds light on the mechanisms responsible for MUN-induced placental insufficiency while identifying therapeutic agents as possible add-on interventions. |
| format | Article |
| id | doaj-art-0434eef25a1d496fae4c173cb4dd36ed |
| institution | Kabale University |
| issn | 0144-3615 1364-6893 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Obstetrics and Gynaecology |
| spelling | doaj-art-0434eef25a1d496fae4c173cb4dd36ed2025-02-07T07:19:27ZengTaylor & Francis GroupJournal of Obstetrics and Gynaecology0144-36151364-68932025-12-0145110.1080/01443615.2025.2460545Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishmentMia Camilliere0Marella R. Verde1Michael S. Wolin2May M. Rabadi3Brian B. Ratliff4Department of Pathology, New York Medical College, Valhalla, NY, USADepartment of Physiology, New York Medical College, Valhalla, NY, USADepartment of Physiology, New York Medical College, Valhalla, NY, USADepartment of Medicine, New York Medical College, Valhalla, NY, USADepartment of Physiology, New York Medical College, Valhalla, NY, USABackground Insufficient nutrition during pregnancy can lead to negative health outcomes for both mother and foetus. Maternal undernourishment (MUN) can be due to many factors like hyperemesis gravidarum or poor access to nutrition. Just as MUN can affect the mother and foetus, it can adversely affect the vital placental interface between the two. We suspect an observed increase in fetuin-B and oxidative stress in MUN placentas could be major players responsible for the placental insufficiency often seen with MUN.Methods To establish a model of MUN during pregnancy, a reduced protein chow was fed to pregnant dams at a caloric deficit. We examined the MUN placentas and the downstream effects of fetuin-B and oxidative stress at the whole organ and trophoblast levels. We examined fetuin-B’s role in trophoblast pathology by measuring apoptosis, proliferation, TLR4 activation, expression of NF-ΚB p65, oxidative stress, and mitochondrial superoxide production. The effects of MUN and fetuin-B on mitochondrial superoxide production, antioxidant levels, metabolism, and electron transport chain complex activity were compared directly. Pharmaceutical interventions were utilised to narrow down specific pathways involved.Results Studies indicated that MUN and oxidative stress upregulated fetuin-B in the placenta. This relationship displayed a positive feedback loop as fetuin-B, in turn, promoted oxidative stress through activation of TLR4. Consequently, MUN, fetuin-B, and oxidative stress promoted apoptosis and reduced proliferative expansion of trophoblast, thereby reducing their quantity. MUN and fetuin-B reduced mitochondrial metabolism and function, promoting mitochondrial dysregulation and superoxide generation in MUN trophoblasts.Conclusions Our study sheds light on the mechanisms responsible for MUN-induced placental insufficiency while identifying therapeutic agents as possible add-on interventions.https://www.tandfonline.com/doi/10.1080/01443615.2025.2460545placentamaternal undernourishmenttrophoblastoxidative stressmitochondriafetuin-b |
| spellingShingle | Mia Camilliere Marella R. Verde Michael S. Wolin May M. Rabadi Brian B. Ratliff Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment Journal of Obstetrics and Gynaecology placenta maternal undernourishment trophoblast oxidative stress mitochondria fetuin-b |
| title | Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment |
| title_full | Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment |
| title_fullStr | Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment |
| title_full_unstemmed | Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment |
| title_short | Fetuin-B and oxidative stress disrupt placental trophoblasts during maternal undernourishment |
| title_sort | fetuin b and oxidative stress disrupt placental trophoblasts during maternal undernourishment |
| topic | placenta maternal undernourishment trophoblast oxidative stress mitochondria fetuin-b |
| url | https://www.tandfonline.com/doi/10.1080/01443615.2025.2460545 |
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