null New RI-MUHC study increases our understanding of infertility
Key step in preparing the egg for fertilization revealed in Nature Communications publication
SOURCE: RI-MUHC. Published this month in Nature Communications, a new study by researchers from the Research Institute of the McGill University Health Centre (RI-MUHC) is a step forward in understanding infertility. Led by Hugh Clarke, PhD, a senior scientist at the RI‑MUHC, the study focuses on the hormonal pathway that triggers ovulation.
“Before an egg can be fertilized, it must undergo a long period of development – several months in humans – within a follicle in the ovary,” explains Hugh Clarke, who is a member of the Child Health and Human Development Program (CHHD) and conducts research at the Centre for Translational Biology at the RI-MUHC. “Then at the time of ovulation, the contact between the egg and the follicle cells that surround it must be broken to allow the sperm access to fertilize the egg. We have discovered the signal that triggers this detachment and the mechanism by which it occurs.”
“The mechanism for breaking contact between the egg and the follicle cells was unknown,” says Laleh Abbassi, PhD, first author of the study and a former graduate student at the RI‑MUHC. “Our paper shows that the same hormone that triggers ovulation also activates the process that breaks the contact between the egg and the follicle cells.”
“The process of breaking contact between the egg and the follicle cells must be precisely timed and regulated. If the contact is broken too quickly, the egg will not complete its development. Too late, and the egg may not be fertilized. Our work clarifies key steps in the pathway.”
— Hugh Clarke
The researchers found that a cell signaling cascade known as the epidermal growth factor receptor (EGFR) pathway, which becomes active at the time of ovulation, instructs the follicle cells to retract specialized finger-like structures that link them to the oocyte. Breaking the contact between the two cell types, this retraction occurs through a remodelling of the cytoskeleton of the follicle cells. The research team was surprised to find that the decision to break contact is made entirely by the follicle cells, with no input from the oocyte.
Adds Hugh Clarke, “The process of breaking contact between the egg and the follicle cells must be precisely timed and regulated. If the contact is broken too quickly, the egg will not complete its development. Too late, and the egg may not be fertilized. Our work clarifies key steps in the pathway.”
By revealing more about the process by which the oocyte becomes detached from the follicle cells at the time of ovulation, the results of this study may lead to new treatments for infertility.
About the study:
Abbassi, L., El-Hayek, S., Carvalho, K.F. et al. Epidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation. Nat Commun 12, 1438 (2021). https://doi.org/10.1038/s41467-021-21644-z
The authors gratefully acknowledge funding from the Canadian Institutes for Health Research, the Fonds de recherche du Québec – Nature et technologies, and the RI-MUHC.
March 23, 2021