# MECHANISMS OF MAMMALIAN FERTILIZATION/POLYSPERMY BLOCK

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1994 · $174,726

## Abstract

Fertilization of mouse eggs initiates a phenomenon termed "egg activation".
Egg activation results in (1) the stimulation of cortical granule (CG)
exocytosis that results in modifications of the zona pellucida (ZP) that
constitute the block to polyspermy, and (2) results in the conversion of a
meiotic cycle to a mitotic one (mitotic activation).  By analogy to
differentiated somatic cells, the sperm may initiate these events by a G
protein-mediated signal transduction pathway that results in the generation
of specific second messengers/ionic changes.

Specific second messengers[inositol 1, 4, 5-triphosphate (IP3) or
activators of protein kinase C (PKC)] elicit the ZP modifications but do
not result in mitotic activation.  These observations suggest that although
both CG exocytosis and mitotic activation are initiated by fertilizing
sperm, different second messenger systems may be generated that
differentially regulate these two responses.  In addition, although G
proteins mediate exocytosis and mitogenic activation in somatic cells,
there are in fact no conclusive data that mammalian egg activation is
mediated by a G-protein-coupled signal transduction cascade.  This proposal
will address (1) the role of these second messengers in differentially
regulating these two components of mouse egg activation, and (2) the role
of G proteins in egg activation.  These studies will use cell biological
and biochemical approaches, including microinjection and in vitro
fertilization of eggs.

The modification of the ZP after fertilization, which constitutes the block
to polyspermy, is thought to be mediated by the contents of the cortical
granules, which are released following fertilization.  There is little
information, however, regarding the contents of CGs, let alone their mode
of action on the ZP modification.  This proposal will address the
characterization and function of the first described mammalian egg cortical
granule protein.  These studies will use cell biological, biochemical, and
molecular approaches, including metabolic labeling of eggs,
immunoprecipitation and immunoblotting, preparation and screening of cDNA
libraries, and isolation and analysis of cDNA clones.
Results of these studies will provide new information regarding (1) the
biochemical basis of egg activation, (2) the role of G proteins in
mediating sperm-induced egg activation, and (3) the characterization and
cloning of the first mammalian cortical granule antigen.

## Key facts

- **NIH application ID:** 2198651
- **Project number:** 5R01HD022732-08
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** GREGORY S. KOPF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $174,726
- **Award type:** 5
- **Project period:** 1987-07-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198651

## Citation

> US National Institutes of Health, RePORTER application 2198651, MECHANISMS OF MAMMALIAN FERTILIZATION/POLYSPERMY BLOCK (5R01HD022732-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198651. Licensed CC0.

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