# GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $762,315

## Abstract

PROJECT SUMMARY / ABSTRACT
Male infertility impacts up to 7% of all men and has been shown to be associated with poor somatic health and
elevated individual and familial cancer risk. Significant epidemiological data links male infertility to poorer
somatic health compared with fertile men, manifesting as increased individual risks for prostate cancer, testis
cancer, colon cancer, cardiovascular disease and reduced life span. Recent work by our group has also
demonstrated that family members of infertile men are at higher risk of testis cancer and both major congenital
anomalies and pediatric cancer. Specifically, much of this work found different associations in men with severe
oligozoospermia (reduced sperm counts) compared with those with azoospermia, suggesting that their etiologies
are fundamentally different. In a follow up study that mined age and cause of death information from the Utah
Population Database (UPDB), we found that individuals with the highest quartile of age-adjusted germline
mutation rates live for five fewer years than those in the lowest quartile. This project aims to study a unique
population to measure mutations in the testis, mature sperm, and somatic tissue to test the hypotheses that
genomic instability underlies reduced fertility, and that genome instability in one’s germline is connected to
increased somatic mutation and mosaicism. We will test this through two aims. 1.) Assessment of whether
subfertile men have higher germline mutation rates than fertile men by examining complex pedigree data to
identify familial associations between male infertility and cancer risk and determine mutation rates in the germline
and somatic cells of 20 oligozoospermic men and 20 hyperzoospermic men. 2.) We will test whether higher
germline mutation rates are predictive of elevated somatic mutation rates and lower sperm counts by using
cadaveric organ donor tissue from testis, sperm, prostate, blood and colon to assess mutation rates. These two
aims will provide foundational datasets for the field and will be able to answer whether higher de-novo mutation
rates are the mechanistic link underlying both male infertility and poor somatic health.

## Key facts

- **NIH application ID:** 10290013
- **Project number:** 1R01HD106112-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Kenneth Ivan Aston
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $762,315
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10290013

## Citation

> US National Institutes of Health, RePORTER application 10290013, GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (1R01HD106112-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10290013. Licensed CC0.

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