Age-related increase in aneuploidy and alteration of gene expression in mouse first polar bodies

Abstract

Purpose To confirm that aneuploidy candidate genes are detectable in the first polar body (PB 1 ) of MII oocytes and to investigate the age-dependent molecular changes in PB 1 . Methods Aged (12-to 15-mo-old) and young (2-mo-old) mice were administered pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotrophin (hCG). MII oocytes were obtained and the first PB was removed. mRNA from each PB and its sibling oocyte was reverse transcribed. Real-time PCR was performed to quantify the expression of six genes (BUB1, CDC20, Filia, MCAK, SGOL1, SMC1A) in single PB. Results We first demonstrated that detection and quantification of transcripts associated with aneuploidy in single mouse oocyte and sibling PB 1 is possible and the relative abundance of mRNA transcripts in a single PB faithfully reflects the relative abundance of that transcript in its sibling oocyte. We further found that transcript levels were significantly lower in aged PBs compared with young PBs (P<0.05). Conclusions Our results suggest that the detection and analysis of polar body mRNA may provide insight in age-related aneuploidy in oocyte. This analysis is a novel concept to investigate the genesis of chromosome abnormality and could potentially assist in the characterization of mechanisms underlying key molecular origin of female meiotic aneuploidy, which would be of great scientific and clinical value.

Ca2+ dynamics in oocytes from naturally-aged mice

“…Naturally-aged mice are an established model of in vivo aging, and have been extensively used to identify age-related changes in numerous cell types, including eggs. Here we used CD1 mice at 12–15 months old, which have been well characterised as a model for maternal age-related egg defects, as measured by aneuploidy levels 20 21 22 23 . Control MII eggs from young CD1 mice and MII eggs from naturally-aged CD1 mice were collected contemporaneously 14 hours after hCG administration.…”

Location and expression of Juno in mice oocytes during maturation

“…In this study, Juno expression on the first polar body membrane is consistent with the fact that oocytes in MII stages express Juno protein on their oolemma, as the first polar body is extruded at the end of the TI stage with a little membrane and a little cytoplasm from the sibling oocyte ( Fabritius et al ., 2011 ). Existence of Juno mRNA on the first polar body has not been determined yet, but the first polar body has a similar mRNA expression as its sibling oocytes in mice and human ( Reich et al , 2011 ; Jiao et al ., 2014 ). More recently, the sperm receptor on the oocyte membrane was reduced in aged mice oocytes ( Dai et al ., 2017 ).…”

A kaleidoscopic view of ovarian genes associated with premature ovarian insufficiency and senescence

“…Mutations of SGO2 led to POI phenotypes in patients with Perrault syndrome 89 whereas knockdown of this gene in mouse oocytes led to defects in meiosis I 88 . Because the paralogues SGO1 is also expressed in mouse oocytes and its decreased expression was correlated with increased aneuploid in aging mice, 90 SGO1 is also a POI candidate gene.…”