# Project 1: Oocyte Developmental Competence and Aging

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $384,442

## Abstract

PROJECT SUMMARY/ABSTRACT 
With the progressive delaying of childbearing age in western society, understanding and treating the decline in 
women's fertility associated with aging is becoming increasingly important. While the causes of premature aging 
of the ovary compared to other organs are largely unknown, it is widely accepted that a decline in oocyte 
competence to develop as an embryo is central to the decline in fertility in women over thirty-five. Several causes 
are thought to be at the basis of this decreased oocyte quality, the most widely accepted being an increase in 
age-related aneuploidy. Oocyte competence to complete meiosis and to develop as an embryo depends on 
complex programs of gene expression. At the end of its growth, oocyte's transcription is silenced and the control 
of gene expression is transferred to the cytoplasm, where a program of selective translation of maternal mRNA 
is executed. Thus, translational regulation is essential for the oocyte to become developmentally competent. Our 
laboratory has shown that this translation program activated in the final stages of oocyte maturation plays a 
critical role for the progression through the meiotic cell cycle, for chromosome trafficking and for preimplantation 
embryo development. Here we propose to test the hypothesis that this oocyte translation program becomes 
progressively defective during female aging. Preliminary data exploring the translation of candidate maternal 
mRNAs in oocytes from aging mouse females support this hypothesis. We propose to further these studies by 
exploring the functionality of the translation program during aging in mice and humans. The first Specific Aim 
will compare the pattern of maternal mRNA translation in oocytes from young and old females. We will use a 
mouse model where ribosomes are tagged in the oocyte, and translating mRNAs will be isolated by 
immunoprecipitation of ribosome/mRNA complexes followed by RNA-Seq. This genome-wide approach will 
define the extent of translational defects that develop with oocyte aging. The second Specific Aim will be devoted 
to understanding the molecular mechanisms at the basis of this defective translation. On the basis of genome- 
wide data suggesting defective expression of RNA binding protein networks and polyadenylation machinery, we 
will investigate the functionality of these components in aging oocytes. With the third Specific Aim, we will test 
the hypothesis that disruption of the translational program recapitulates the phenotype associated with aging. 
We will use genetic models of haploinsufficiency and SiRNA mediated knockdown to destabilize the translational 
program in young oocytes and determine whether oocyte developmental competence is compromised as it is 
during aging. To consolidate these findings, we will relate the observations made in a rodent model to human 
oocytes. We will explore whether translation is defective in oocytes from aging women and explore whether 
defe...

## Key facts

- **NIH application ID:** 10133109
- **Project number:** 5P50HD055764-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Marco Conti
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,442
- **Award type:** 5
- **Project period:** 2007-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133109

## Citation

> US National Institutes of Health, RePORTER application 10133109, Project 1: Oocyte Developmental Competence and Aging (5P50HD055764-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10133109. Licensed CC0.

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