# Oocyte mitochondrial activity regulates embryo telomere reprogramming

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $513,019

## Abstract

PROJECT SUMMARY
Telomeres, the repetitive DNA at the ends of chromosomes, shorten during every cell division except in very
exceptional circumstances; in particular, rapid telomere elongation in the embryo is essential for ‘resetting’
telomere length. Long telomeres at birth protect genome stability and are associated with good health and
increased longevity, while shorter telomeres are associated with age-related diseases and early mortality. We
have discovered that embryos of obese females exhibit fundamental deficiencies during preimplantation
development that result in offspring having shorter telomeres, providing an explanation for the increased risk of
poor health and early mortality in adult children of obese women. Importantly, we have also determined that
enhancement of mitochondrial bioenergetics in the oocytes of obese mothers restored the capacity for telomere
lengthening during blastocyst formation. This indicates an important but previously unappreciated molecular link
between mitochondria and telomeres and is the first evidence of a regulatory mechanism by which maternal
physiology determines offspring aging and lifespan. The proposed work will define the molecular mechanisms
by which telomeric DNA is extended during preimplantation embryogenesis, including in a clinically relevant
nonhuman primate (NHP) model, establishing completely new concepts around the developmental programming
of healthy aging. We will use cutting-edge micro-manipulation and molecular assessments of genome activation
to determine how oocyte mitochondrial membrane potential is linked to embryo transcriptional reprogramming.
Further, we will identify actionable therapeutic strategies for ensuring the integrity of these developmental
processes in physiological contexts where they are defective. As maternal obesity rates continue to rise,
understanding the impact of diet and obesity on embryo telomere reprogramming has important clinical
ramifications because telomere length at birth is a well-understood determining factor for future disease risk.
Identifying targets and therapeutic approaches to positively manipulate this biology will provide opportunities to
protect essential molecular reprogramming events at conception and during early embryogenesis that ultimately
improve lifetime health.

## Key facts

- **NIH application ID:** 10881074
- **Project number:** 1R01HD111435-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jon D Hennebold
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $513,019
- **Award type:** 1
- **Project period:** 2024-09-05 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881074

## Citation

> US National Institutes of Health, RePORTER application 10881074, Oocyte mitochondrial activity regulates embryo telomere reprogramming (1R01HD111435-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10881074. Licensed CC0.

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