# SLO3 KO MOUSE: A TOOL TO REVEAL VOLTAGE-DEPENDENT PROCESSES IN SPERM FERTILITY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $326,726

## Abstract

PROJECT SUMMARY
Infertility affects 10% to 15% of couples worldwide, and a male factor contributes to around 50% of these
cases. Male infertility is diagnosed predominantly on the results of standard semen analysis, which
provides information about sperm count, morphology, and motility. However, many sperm samples from
infertile men pass this standard analysis but, for unknown reasons, still lack the ability to fertilize an egg.
Thus, to improve male fertility, our long-term goal is to reveal the basic mechanisms by which sperm
become competent to fertilize an egg and to identify new diagnostic strategies and therapeutic targets.
In many mammalian species membrane hyperpolarization (when the intracellular voltage becomes more
negative) is a key event in sperm becoming competent to fertilize an egg (capacitation). We previously
showed that sperm from mice that lack the sperm-specific SLO3 K+ channels cannot undergo membrane
hyperpolarization and are infertile. Hyperpolarization is also associated with human sperm capacitation,
and a depolarized membrane is associated with impaired fertilization capacity in human sperm. However,
the ion channels responsible for regulating membrane potential in human sperm are uncertain. In this
proposal we aim to determine the ion permeabilities that underlie membrane potential changes in human
sperm and how membrane hyperpolarization regulates changes in intracellular calcium (another key
aspect of sperm capacitation). We propose that human sperm membrane potential is regulated by the
potassium (K+) channel SLO3 as in mouse sperm and that SLO3 dysfunction might be responsible for
some cases of male idiopathic infertility. These studies might also produce a valuable clinical tool –
measurement of sperm membrane potential using voltage sensitive dyes - to predict human sperm
fertilization capacity. Additionally, if SLO3 plays an essential role in human fertilization in humans as it
does in mice, this sperm-specific channel would provide a new, non-hormonal target for a male
contraceptive.

## Key facts

- **NIH application ID:** 9962433
- **Project number:** 5R01HD069631-08
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Celia M Santi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,726
- **Award type:** 5
- **Project period:** 2011-09-02 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962433

## Citation

> US National Institutes of Health, RePORTER application 9962433, SLO3 KO MOUSE: A TOOL TO REVEAL VOLTAGE-DEPENDENT PROCESSES IN SPERM FERTILITY (5R01HD069631-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9962433. Licensed CC0.

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