# Accumulation, Storage, and Release of Sperm in the Oviduct

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2024 · $337,580

## Abstract

Project Summary
Fertility depends on successful fertilization and early development, processes that occur in the oviduct. Common therapies
for human infertility, such as in vitro fertilization and intracytoplasmic sperm injection, are expensive and increase the
risks of a variety of problems. More knowledge of how the oviduct interacts with sperm, the cumulus-oocyte complex
(COC), and the developing embryo may improve fertility and reduce the need for therapies or lead to the development of
improved therapies (i.e. improvements in IVF). The oviduct serves as a reservoir for sperm, after semen deposition and
before fertilization. Binding to the oviduct maintains sperm viability and suppresses motility. Sperm are released to move
to the upper oviduct (ampulla) to fertilize oocytes. There are many gaps in this model of sperm-oviduct interaction but our
studies have begun to fill some of these gaps. We have used a glycomic approach to screen hundreds of glycans and found
that glycans with affinity for porcine sperm have either of two motifs, sulfated Lewis X trisaccharide or branched 6-
sialylated complex glycans. We also identified two candidate receptors for both glycans on the sperm membrane,
PKDREJ and ADAM5, that were not known to bind glycans. Notably, mouse sperm deficient in PKDREJ and other
ADAMs do not accumulate beyond the utero-tubal junction, but it is not known if this is due to a problem in
binding and retention in the oviduct. Remarkably, if these glycans are immobilized on beads or microscope slides, they
can extend sperm lifespan, much like binding to oviduct cells prolongs the lifespan of sperm. Finally, we found that COCs
secrete progesterone that signals sperm release from the lower oviduct by inducing hyperactivation so sperm can move
toward the site of fertilization. The Specific Aims of this renewal will provide a mechanistic understanding of how sperm
bind the oviduct, how binding prolongs sperm lifespan, and how these results may be translated to improve IVF. Aim 1:
To determine the function of PKDREJ and ADAM5 in sperm by blocking each protein and mutating each gene in
swine. Sperm from pigs that have mutations in these genes have been produced. Sperm that are deficient in each of these
proteins will be examined to determine if their ability to bind oviduct cells and their fertility are affected. Aim 2. To
determine if sperm binding to glycans diminishes oxidative phosphorylation and the citric acid cycle to lengthen
sperm lifespan. Sperm bound to immobilized glycans will be examined to ascertain the specific metabolic changes that
are induced and the intracellular signaling that leads to these changes. Aim 3. To determine if oviduct glycans select
superior sperm for storage and in vitro fertilization. We will examine whether sperm selected by glycan adhesion have
improved characteristics themselves and also produce embryos that more closely resemble in vivo-produced embryos by
comprehensive analysis of embryo transcriptome...

## Key facts

- **NIH application ID:** 10928820
- **Project number:** 5R01HD095841-06
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** DAVID Joel MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $337,580
- **Award type:** 5
- **Project period:** 2018-09-04 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928820

## Citation

> US National Institutes of Health, RePORTER application 10928820, Accumulation, Storage, and Release of Sperm in the Oviduct (5R01HD095841-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10928820. Licensed CC0.

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