Circ_0081343 promotes autophagy and alleviates pyroptosis via PI3 K/AKT/HIF-1α axis in hypoxia-induced fetal growth restriction of mice
Objective: Fetal growth restriction (FGR) is a serious pregnancy complication associated with an increased risk of perinatal morbidity and mortality. Notably, circular RNAs (circRNAs) significantly influence physiological development and disease pathogenesis. We reported previously that lower circ_0...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Animal Cells and Systems |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19768354.2025.2498932 |
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| Summary: | Objective: Fetal growth restriction (FGR) is a serious pregnancy complication associated with an increased risk of perinatal morbidity and mortality. Notably, circular RNAs (circRNAs) significantly influence physiological development and disease pathogenesis. We reported previously that lower circ_0081343 expression is associated with placental trophoblast dysfunction. However, only a few studies have reported the role of circRNAs in FGR in vivo. Therefore, we investigated the effects of circ_0081343 overexpression in the FGR mouse model induced by maternal hypoxia. Methods: Pregnant C57BL/6 mice were kept under hypoxic conditions (10.5% O2) from gestational days 11–17.5, whereas control mice were kept in normal oxygen conditions throughout the gestation period. The animals were sacrificed on the 18.5th day of gestation for prenatal observation. We recorded the maternal body weight, fetal body weight, crown-rump length, and placental weight. Subsequently, we assessed the expression of autophagy, pyroptosis-related protein, and PI3 K/AKT/HIF-1α pathway molecules in placental tissues using RT-PCR, western blotting, ELISA, and immunohistochemistry analysis. Results: We observed low mmu_circ_0081343 expression in the placental tissues of the FGR mouse. However, the expression increased following the injection of adenovirus-mmu-circ_0081343. The overexpression of mmu-circ_0081343 alleviated FGR symptoms in the pregnant mice, including increasing fetal body and placental weight and ameliorating histological injury of the placenta. Additionally, overexpression of mmu-circ_0081343 upregulated Beclin1 expression, increased the LC3II/I ratio, and downregulated P62 expression, while suppressing the PI3 K/AKT/HIF-1α pathway. Conclusions: circ_0081343 alleviated gestational hypoxia-induced placental dysfunction and fetal growth restriction (FGR) by promoting autophagy and inhibiting pyroptosis, potentially through the PI3 K/AKT/HIF-1α pathway. |
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| ISSN: | 1976-8354 2151-2485 |