# Beyond spermatogenesis: Additional roles of seminal fluid fatty acids in male fertility and age-related reproductive success

> **NIH NIH R21** · MICHIGAN STATE UNIVERSITY · 2022 · $243,375

## Abstract

Project Summary/Abstract
In many animals, the seminal fluid plays a major role in male reproductive success. Proteins in the seminal fluid
have significant effects on multiple features of male and female reproductive physiology. However, relatively little
is known about a second major component of seminal fluid, lipids, beyond their roles as sperm membrane
constituents. The overall objectives in this proposal are to i) identify differences in the lipidomic and transcriptomic
profiles of seminal fluid in young and aged males; and ii) directly test how manipulating the lipid profile of seminal
fluid impacts male reproductive success. This proposal will address the hypothesis that the seminal fluid lipidome
influences male fertility and changes with age, thus contributing to the decline of aging-related reproductive
success. This hypothesis is supported by the applicants’ published studies showing that fatty acids and related
lipids in the seminal fluid of Drosophila males are essential for male fertility. Both transposon-mediated knockout
and RNAi knockdown of a key fatty acid biosynthesis enzyme in the male ejaculatory bulb (EB), an organ that is
not involved in spermatogenesis, causes a significant decrease in male fertility, strongly supporting the
contribution of seminal fluid fatty acids to male reproductive success. In contrast to mammalian models, use of
Drosophila allows seminal fluid lipids produced in the EB to be manipulated without interfering with
spermatogenesis in the testes. Powerful genetic manipulation in combination with lipidomic and transcriptomic
analysis will be used to pursue the following aims: Aim 1 of the proposal will test a prediction of the hypothesis
that changes in the composition of seminal fluid fatty acids and other lipids accompany aging-related loss of
fertility. Using multiple mass spectrometry methods, the seminal fluid lipidome will be characterized in young and
old males in order to identify features of the lipid profile that correlate with high and low fertility. Aim 2 will test a
second prediction of the hypothesis, that the expression of fatty acid synthesis genes in the EB changes in aging
males, leading to a shift in fatty acid and related lipid composition in the seminal fluid. Transcriptomic analysis of
the EB from young and old males followed by functional validation with genetic knockdown will identify genes
that underlie age-related changes in seminal fluid lipid content. In Aim 3, a direct test of the hypothesis will be
performed by assessing whether male fertility improves or declines upon genetic manipulation of the seminal
fluid fatty acid content. The expected outcomes are significant because they are likely to identify new
mechanisms that modulate male and female reproductive physiology and may point to previously unrecognized
causes of idiopathic male infertility. The proposed study is innovative because it is expected to identify a new
class of molecules and novel biochemical pathways that ...

## Key facts

- **NIH application ID:** 10526745
- **Project number:** 1R21AG075618-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Hock Wee Henry Chung
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $243,375
- **Award type:** 1
- **Project period:** 2022-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526745

## Citation

> US National Institutes of Health, RePORTER application 10526745, Beyond spermatogenesis: Additional roles of seminal fluid fatty acids in male fertility and age-related reproductive success (1R21AG075618-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10526745. Licensed CC0.

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