Effect of ACY-1215 on cytoskeletal remodeling and histone acetylation in bovine somatic cell nuclear transfer embryos

The latest studies indicated that in addition to alterations in abnormal chromosome epigenetic modifications, the abnormal cytoskeletal changes are also an important cause for the developmental failure of somatic cell nuclear transfer (SCNT) embryos. In the present study, the effects of ACY-1215, a specific inhibitor of HDAC6, on the acetylation of alpha-tubulin, histone epigenetic modification, spindle formation and embryonic development of early bovine SCNT embryos were studied. The results showed that acetylation of alpha-tubulin, H3K9, and H4K16 was significantly lower in SCNT embryos than in vitro fertilization (IVF) embryos. After ACY-1215 treatment, the acetylation level of alpha-tubulin, H3K9, and H4K16 of SCNT embryos was closer to that of IVF embryos. ACY-1215 treatment reduced spindle abnormalities, delayed the time of first cleavage of embryos, increased the total cell number and trophectoderm cells numbers, and reduced apoptosis in SCNT blastocysts. ACY-1215 regulated the process of embryonic epigenetic modification and cytoskeletal protein acetylation, corrected abnormal development of SCNT embryos, and improved SCNT embryonic development potential. (c) 2022 Published by Elsevier Inc.

Automated summary

Recent studies have shown that abnormal cytoskeletal changes are an important cause of developmental failure in somatic cell nuclear transfer (SCNT) embryos, in addition to alterations in abnormal chromosome epigenetic modifications. In this study, the effects of ACY-1215, a specific inhibitor of HDAC6, on the acetylation of alpha-tubulin, histone epigenetic modification, spindle formation, and embryonic development of early bovine SCNT embryos were investigated. The results showed that ACY-1215 treatment improved the acetylation level of alpha-tubulin and histone proteins, corrected spindle abnormalities, delayed cleavage timing, increased cell numbers, and reduced apoptosis in SCNT blastocysts. ACY-1215 was found to regulate the process of embryonic epigenetic modification and cytoskeletal protein acetylation, leading to improved SCNT embryonic development potential.