Development, Live Birth and Fertility in Mouse Oocytes Penetrated by Spermatids Exposed to the HDAC Inhibitor...

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.