# Linking Fertility-Associated Gene Polymorphisms to Aberrant Sperm Phenotypes

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $205,753

## Abstract

Sutovsky, Peter - PD
SUMMARY
The present project is directly relevant to the goals of RFA PAR-13-204, Dual Purpose with Dual Benefit: Research in
Biomedicine and Agriculture Using Agriculturally Important Domestic Species. It will be the first project to systematically
link the genetic traits affecting male fertility to sperm phenotypes easily measurable in a human/animal semen sample.
Whole genome sequencing has identified a large number of gene polymorphisms with the potential to affect male
fertility in humans and livestock. However, there is very little understanding of how these polymorphisms may affect the
phenotypes of spermatozoa, their fertilizing ability and their influence on pre-embryo development and early embryo
loss. We hypothesize that unique mutations/polymorphisms in genes expressed during spermatogenesis and pre-
embryo development (further “fertility associated genes”) are responsible for male subfertility and for early embryo loss
during pregnancy. Our goal is to link these genetic traits to sperm phenotypes measurable in a semen sample and
reflected by the males’ fertility in vivo and in vitro. We chose artificial insemination (AI) bulls as model system because
their genotypes are publically accessible, they have extensive fertility records from AI services, and their fertility in vivo
correlates with their in vitro fertility. We have identified 3,601 candidate fertility-related genes with loss-of-function
LOF) polymorphisms in the whole genome sequences of 219 bulls representing 18 breeds and performed phenotype
analysis on several candidate gene products that revealed significant differences between fertile but under-performing
bulls with less than satisfactory AI fertility and top bulls with highest AI fertility. Both genes also show non-synonymous
polymorphisms in humans.
AIM 1 of this project will employ genotyping and in silico search to identify genetic differences between fertile and
subfertile bulls, including polymorphisms associated with high/low conception rates in AI, as well as those prevalent in
yearling bulls that failed Breeding Soundness Evaluation (BSE). We hypothesize that fertile bulls fall on the opposite ends
of fertility range due to identifiable polymorphisms in relatively few genes controlling spermatogenesis, sperm
phenotype and sperm function. AIM 2 will use a combination of proteomic and cell biological approaches, including but
not limited to innovative image based flow cytometry (IBFC), to link genetic fertility traits to the sperm phenotypes
easily measurable in a semen sample. Based on the identification of sperm antigens expressed only or predominantly by
carriers of the fertility-affecting mutations, we will develop multiplex, flow cytometry-based high throughput semen
quality assays for routine use in field AI. We hypothesize that a non-synonymous change in a gene controlling
spermatogenesis or sperm function will alter the sperm phenotype via change in the quantity, localization and/or
fu...

## Key facts

- **NIH application ID:** 9977699
- **Project number:** 5R01HD084353-05
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** PETER Sutovsky SUTOVSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,753
- **Award type:** 5
- **Project period:** 2016-09-12 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977699

## Citation

> US National Institutes of Health, RePORTER application 9977699, Linking Fertility-Associated Gene Polymorphisms to Aberrant Sperm Phenotypes (5R01HD084353-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977699. Licensed CC0.

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