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. 2011 Oct 1;10(19):3253-6.
doi: 10.4161/cc.10.19.17585. Epub 2011 Oct 1.

TAp73 Is Downregulated in Oocytes From Women of Advanced Reproductive Age

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TAp73 Is Downregulated in Oocytes From Women of Advanced Reproductive Age

Maria Rosa Guglielmino et al. Cell Cycle. .
Free PMC article

Abstract

Studies on oocyte transcriptome are important to understand the biological pathways involved in oogenesis, totipotence and early embryonic development. Moreover, genes regulating physiological pathways in gametes could represent potential candidates for reproductive disorders. In addition to oocyte specific transcription factors, also the members of the p53 family could be etiologically involved due to their biological functions. In fact, their role in the control of cell cycle, apoptosis, and germ-line genome stability is well known. Female reproductive aging is one of the causes of fertility reduction and it is often associated with egg aneuploidy increase. In order to verify the potential involvement of p73 in reproductive aging, we determined its expression in single mature MII oocytes from two groups of women, younger than 35 or older than 38 years, respectively. We found that TAp73 isoforms are down regulated in oocytes from women older than 38 years. We confirmed these data in pools of mouse oocytes. TAp73 down regulation in oocytes from women of advanced reproductive age could explain both the reduction of fertility and the increase of newborns with chromosomal abnormalities.

Figures

Figure 1
Figure 1
(A) The histogram shows the fold change (RQ) mean as the ln 2−ΔΔCt in single human oocytes. We calculated the relative levels of mRNA expression in each sample according to the 2−ΔΔCt method, using HPRT for normalization and young oocytes as calibrators. Y error bars represent variability among different samples, showing the maximum and minimum FC values. To statistically evaluate the results, young and old oocytes ΔCt were analyzed by unpaired (two sample) Student's t-test. (B) The histogram shows the fold change (RQ) mean as the ln 2−ΔΔCt in pools of mouse oocytes. The experiment was performed in triplicate and the data are reported as mean ± SD (C). Methylation analysis was performed by bisulfite conversion and pyrosequencing to detect the methylation status of 6 CpGs in the CpG island, located at the promoter region of mouse TA p73 gene. The image shows that methylated CpG sites were less than 5% in both young (1) and old (2) mouse oocytes. Each sample was analyzed in duplicate, including an internal control, to measure the extent of bisulfite modification.

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