# Regulation of Ca2+ influx in mouse oocytes and eggs during maturation and fertilization to improve assisted reproductive technologies and modulate fertility

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $271,379

## Abstract

There is a persistent gap in our knowledge of the molecules and mechanisms that mediate Ca2+ influx
into oocytes and eggs. Ca2+ influx is required for egg activation and embryo development in all mammals,
including human beings. This gap in our knowledge therefore represents a serious impediment, as until
it is filled we cannot physiologically modulate Ca2+ influx or objectively diagnose and treat infertility
associated with disturbances in Ca2+ homeostasis. The long-term goal is to understand how Ca2+
homeostasis is regulated in oocytes and eggs and identify its molecular effectors. The objective here is
to identify the Ca2+ channel(s) that mediate Ca2+ influx during maturation and fertilization and characterize
their regulatory mechanisms. Mouse oocytes/eggs are a great model because they display distinctive
Ca2+ entry during maturation and fertilization, and Ca2+ release is required for egg activation. The central
hypothesis is that expression and/or distinct regulation of underdetermined Ca2+ channels on the plasma
membrane underlies Ca2+ influx in oocytes, its inactivation during maturation and its recovery after
fertilization. This hypothesis was conceived based on extensive preliminary data. The rationale for this
research is that once the channels are identified, a better understanding of the molecular determinants
of oocyte maturation and fertilization will be gained. The findings here also have the potential to translate
into therapeutic methods to assist infertile couples in this country. We plan to test our central hypothesis
by pursuing the following specific aims: 1) Identify the Ca2+ channel(s) that mediate Ca2+ influx in oocytes
prior to and during maturation; and 2) Identify the Ca2+ influx channel(s) that support oscillations after
fertilization. Under Aim 1, Ca2+ imaging, pharmacology, conditional knockout mice, and electrophysiology
will be used to identify the active channel(s) and to assess the impact of Ca2+ influx on maturation; the
role of a TRPM7-like current recently discovered by the applicant and collaborators will be closely
examined. Under Aim 2, the signaling mechanism(s) whereby fertilization stimulates Ca2+ influx and the
contributing channel(s) will be determined. A novel approach that overcomes the inactivation of Ca2+
influx in eggs will facilitate these studies. Genetic models and electrophysiology will confirm the function
of these channel(s) during fertilization. The research in this application is innovative because it combines
electrophysiology, pharmacology and new KO lines, approach that has served to identify two new
channels in oocytes, including TRPM7, whose global deletion is embryonic lethal at E7.5. The
contribution of the proposed project is significant because it is expected to allow physiological modulation
of Ca2+ entry in oocytes and eggs that will produce new conditions and activation protocols for use in the
clinic. It will also expand our understanding of the impact of Ca2+ homeostasis on ...

## Key facts

- **NIH application ID:** 10167751
- **Project number:** 5R01HD092499-04
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Rafael Antonio Fissore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $271,379
- **Award type:** 5
- **Project period:** 2018-08-17 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167751

## Citation

> US National Institutes of Health, RePORTER application 10167751, Regulation of Ca2+ influx in mouse oocytes and eggs during maturation and fertilization to improve assisted reproductive technologies and modulate fertility (5R01HD092499-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167751. Licensed CC0.

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