Insufficient histone-3 lysine-9 deacetylation in human oocytes matured in vitro is associated with aberrant meiosis

摘要

Objective: To characterize histone acetylation during meiosis in human oocytes matured in vitro or in vivo. Design: Experimental study. Setting: University reproductive medical center. Patient(s): Patients undergoing routine intracytoplasmic sperm injection (ICSI) cycles. Intervention(s): Immature and mature oocytes were collected from patients undergoing intracytoplasmic sperm injection. Main Outcome Measure(s): Immunohistochemical assessment of the levels of acetylated lysine-9 of histone-3 (H3K9) and lysine-12 of histone-4 (H4K12) combined with spindle and chromosome configurations in in vitro- and in vivo-matured human oocytes. Transcript levels of histone deacetylases (HDACs) 1 and 2 were measured by single-cell quantitative polymerase chain reaction. Result(s): Acetylation of H3K9 and H4K12 decreased during human oocyte maturation. Residual H3K9 acetylation was found in 37.7% of oocytes matured in vitro, compared with 11.8% in oocytes matured in vivo. Abnormal metaphase spindle was more frequent in oocytes with residual histone acetylation than without (51.6% vs. 25.4%, respectively). Treatment with the HDAC inhibitor trichostatin A increased the incidence of an abnormal metaphase but had no adverse effect on maturation efficiency. Furthermore, expression of HDAC1 transcripts was significantly lower in oocytes matured in vitro versus in vivo. Conclusion(s): Reduced HDAC1 expression and insufficient histone deacetylation are associated with metaphase defects in human oocytes matured in vitro.