Loss of HDAC3 contributes to meiotic defects in aged oocytes.

Abstract:

:Maternal age-related decline in oocyte quality is associated with meiotic defects, but the underlying mechanisms remain to be explored. Histone deacetylase 3 (HDAC3) has been shown to govern multiple cellular events via deacetylating diverse substrates. We previously found that HDAC3 could promote meiotic apparatus assembly in mouse oocytes. In the present study, we identified a substantial reduction in HDAC3 protein in oocytes from old mice. Importantly, overexpression of HDAC3 in old oocytes not only partially prevents spindle/chromosome disorganization, but also significantly lowers the incidence of aneuploidy. Meanwhile, we noticed the elevated acetylation level of α-tubulin in oocytes derived from old mice. By employing site-directed mutagenesis, we showed that acetylation-mimetic mutant tubulin-K40Q disrupts the kinetochore-microtubule attachments and results in the assembly failure of meiotic apparatus in mouse oocytes. Importantly, forced expression of tubulin-K40R (nonacetylatable-mimetic mutant) was capable of alleviating the defective phenotypes of oocytes from aged mice. To sum up, this study uncovers that loss of HDAC3 represents one potential mechanism mediating the effects of advanced maternal age on oocyte quality.

journal_name

Aging Cell

journal_title

Aging cell

authors

He Y,Li X,Gao M,Liu H,Gu L

doi

10.1111/acel.13036

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

e13036

issue

6

eissn

1474-9718

issn

1474-9726

journal_volume

18

pub_type

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