# Fertilization-induced maturation of cortical ER clusters in oocytes; impact of maternal age

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $578,455

## Abstract

PROJECT SUMMARY/ABSTRACT
Cortical ER structure is a key aspect of oocyte quality as exemplified in mammals where unique `ER clusters'
become positioned in close proximity to the plasma membrane (PM). Our recent in vivo studies demonstrate
the presence of hereto unknown actin fenestrae within cortical actin layer, in addition the ER clusters were
centrally located within these fenestrae and sperm binding occurred preferentially over these fenestrae.
Another novel observation was that upon sperm fusion the oocyte ER clusters undergo a maturational event
involving an increase in volume, docking to fenestrae in the actin layer. This led us to a hypothesis that the PM
overlying ER clusters is enriched in sperm binding proteins that promote close interaction between the sperm,
oocyte PM, and the ER cluster. Temporal and mechanistic studies are necessary to elucidate the role of the
oocyte cortical actin fenestrae in the establishment of sperm binding sites as well as the role of the sperm
PLCζ released from the sperm head in mediating the ER cluster maturational changes. The presence of
unique actin fenestrae led to a second hypothesis that actin remodeling proteins, RhoA and cdc42, could
modulate sperm binding sites, cortical ER cluster formation via the actin fenestrae. Lastly, we observed that
oocytes from aged female mice exhibited abnormal ER structure and varied considerably in their ability to form
ER clusters in response to fertilization. This finding led us to propose a third hypothesis where maternal aging
disrupts actin fenestrae and Ca2+ oscillations, causing defects in ER cluster maturation and reduced fertility.
Our findings suggest a new paradigm wherein the oocyte responds to sperm binding/fusion by ER cluster
maturation, then establishes close interaction with the sperm during its incorporation into the egg. Testing of
the hypotheses presented in this proposal will lead to an enhanced understanding of the fertilization process,
and potential mechanisms for improving Assisted Reproduction Technologies such as ICSI and protocols for
reproductively aged oocytes as well as potential new contraceptive targets that block fertilization.

## Key facts

- **NIH application ID:** 10891699
- **Project number:** 5R01AG083248-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** LANE K. CHRISTENSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $578,455
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891699

## Citation

> US National Institutes of Health, RePORTER application 10891699, Fertilization-induced maturation of cortical ER clusters in oocytes; impact of maternal age (5R01AG083248-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10891699. Licensed CC0.

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