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Updated: May 12, 2026
Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
Development, Live Birth and Fertility in Mouse Oocytes Penetrated by Spermatids Exposed to the HDAC Inhibitor
Seiji Watanabe1, Youichi Takemoto2, Rei Inoue2
1Department of Anatomical Science Hirosaki University Graduate School of Medicine Hirosaki Japan.
Purpose:
In mouse embryos derived from round spermatid injection (ROSI), low developmental potential due to abnormal histone modification is improved by histone deacetylase (HDAC) inhibitors. However, some studies suggest that the use of such inhibitors leads to the birth of hypomorphic offspring. We examined the genetic risk of Scriptaid on mouse ROSI embryos over two generations.
Methods:
Oocytes were penetrated by spermatids treated with Scriptaid (250 nM 10 min) and transferred to host mothers. After the offspring were born and matured, some first-generation males and females were mated to obtain second-generation offspring. One-cell ROSI embryos treated with Scriptaid (250 nM 16 h) underwent the same process.
Results:
Scriptaid reduced H3K9me3 residues in the spermatid nuclei and in the male pronuclei of ROSI embryos, resulting in increased blastocyst formation and live birth rates compared with the untreated group. All offspring exposed to Scriptaid had normal body weight and external appearance and subsequently grew as well as the IVF offspring. Additionally, all second-generation offspring were also healthy.
Conclusion:
Scriptaid improved the developmental potential of ROSI embryos, and no clear teratogenic effect was observed in the live offspring, suggesting that Scriptaid is safer than Trichostatin-A, which has been reported to induce hypomorphic offspring in ROSI.
Insights
Scriptaid enhances round spermatid injection (ROSI) in mice by improving embryo development and birth rates. This histone deacetylase inhibitor showed no teratogenic effects in offspring over two generations, indicating improved safety over other treatments.
Area of Science:
- Reproductive biology
- Epigenetics
- Developmental toxicology
Background:
- Round spermatid injection (ROSI) in mice can result in low developmental potential due to abnormal histone modifications.
- Histone deacetylase (HDAC) inhibitors are used to improve ROSI outcomes, but concerns exist regarding potential hypomorphic offspring.
- Scriptaid is an HDAC inhibitor with potential applications in improving ROSI efficiency.
Purpose of the Study:
- To evaluate the genetic safety and efficacy of Scriptaid in mouse ROSI embryos across two generations.
- To assess the impact of Scriptaid on histone modification (H3K9me3) and subsequent developmental potential of ROSI embryos.
- To compare the safety profile of Scriptaid with other HDAC inhibitors like Trichostatin-A in the context of ROSI.
Main Methods:
- Spermatids were treated with Scriptaid (250 nM) before oocyte penetration for ROSI.
- ROSI embryos were treated with Scriptaid (250 nM) at the one-cell stage.
- Offspring from treated ROSI embryos were bred to produce a second generation to assess long-term effects.
Main Results:
- Scriptaid treatment reduced H3K9me3 levels in spermatid and pronuclei, enhancing blastocyst formation and live birth rates.
- Offspring exposed to Scriptaid exhibited normal growth, body weight, and external appearance, comparable to in vitro fertilization (IVF) controls.
- All second-generation offspring were healthy, indicating no transgenerational adverse effects.
Conclusions:
- Scriptaid effectively improves the developmental potential of ROSI embryos.
- No significant teratogenic effects were observed in Scriptaid-treated offspring over two generations.
- Scriptaid appears to be a safer alternative to Trichostatin-A for improving ROSI outcomes.
Related Concept Videos
01:41Spermatogenesis
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