Adverse Outcome Pathway on histone deacetylase inhibition leading to testicular atrophy
The present AOP describes inhibition of histone deacetylase resulting in testicular
atrophy. Histone deacetylase inhibitors (HDIs) are approved as anti-cancer drugs since
HDIs have apoptotic effects in cancer cells. The intracellular mechanisms of induction
of the spermatocyte apoptosis by HDIs are suggested as histone deacetylase (HDAC)
inhibition as MIE, histone acetylation increase, disrupted cell cycle, apoptosis,
and spermatocyte depletion as KEs. The adverse outcome has been defined as testicular
atrophy. The HDIs inhibit deacetylation of the histone, leading to an increase in
histone acetylation. The apoptosis induced by disrupted cell cycle leads to spermatocyte
depletion and testis atrophy. Testicular toxicity is of interest for human health
risk assessment especially in terms of reproductive and developmental toxicity, however,
the testicular toxicity has not been fully elucidated. This AOP may be one of the
pathways induced by HDIs, which suggests the pathway networks of protein hyperacetylations.
Published on October 15, 2021
In series:OECD Series on Adverse Outcome Pathwaysview more titles