Desarrollo, Nacimiento Vivo y Fertilidad en Oocitos de Ratón Penetrados por Espermatidas Expuestas al Inhibidor de...

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.

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.

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.

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.