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Published on: January 12, 2020
Ti3C2 nanosheet-induced autophagy derails ovarian functions
Limei Yang1,2, Zhiting He3, Le Hu4
1Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, No. 120 Longshan Road, Yubei District, Chongqing, 401147, China.
Titanium carbide (Ti3C2) nanosheets accumulate in ovaries, causing autophagy dysfunction and disrupting follicular development. This leads to altered hormone levels and potential female reproductive toxicity.
Area of Science:
- Biomedical Engineering
- Materials Science
- Toxicology
Background:
- Two-dimensional ultrathin Ti3C2 (MXene) nanosheets are used in biomedical applications.
- Previous studies noted Ti3C2 accumulation in testes and placenta.
- Ovarian translocation and damage by Ti3C2 nanosheets remain unclear.
Purpose of the Study:
- Investigate Ti3C2 nanosheet translocation to ovaries.
- Assess Ti3C2-induced ovarian damage and functional impairment.
- Elucidate the underlying mechanisms of Ti3C2 ovarian toxicity.
Main Methods:
- Established a mouse model with intravenous Ti3C2 nanosheet injections.
- Analyzed ovarian histology, hormone levels (FSH, LH, E2, P4, T), and autophagy markers (Beclin1, ATG5, LC3II/I, P62).
- Utilized KGN cells for in vitro validation of autophagy's role in hormone secretion.
Main Results:
- Ti3C2 nanosheets entered ovaries and granulosa cells, reducing follicle counts.
- Follicle reduction correlated with altered FSH, LH, E2, P4, and T levels.
- Ti3C2 activated autophagy via PI3K/AKT/mTOR, causing autophagic flux blockade and oxidative stress.
- Autophagy modulation in KGN cells affected estradiol and progesterone secretion.
Conclusions:
- Ti3C2 nanosheet-induced ovarian hormone secretion is mediated by autophagy activation and flux impairment.
- Autophagy dysfunction contributes to Ti3C2-induced damage in ovarian granulosa cells.
- This study reveals mechanisms of Ti3C2-induced female reproductive toxicity.
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