AUTHOR=Shafqat Areez , Kashir Junaid , Alsalameh Sulaiman , Alkattan Khaled , Yaqinuddin Ahmed 

TITLE=Fertilization, Oocyte Activation, Calcium Release and Epigenetic Remodelling: Lessons From Cancer Models

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.781953

DOI=10.3389/fcell.2022.781953

ISSN=2296-634X

ABSTRACT=Oocyte activation deficiency (OAD) is  the basis  of Total Fertilization Failures (TFF) and is attributed to mutations in the PLCζ gene – termed male factor infertility. This derives  abnormal Ca2+ oscillations and could be the main cause of primary disruptions in the gene expression of Ca2+-related proteins. Epigenetic mechanisms are universally accepted as key regulators of gene expression. However, epigenetic dysregulations have not been considered as potential mechanisms of oocyte-borne OAD. Herein, we discuss changes in DNA methylome during oogenesis and embryogenesis. We further highlight  key pathways comprising the oocyte Ca2+ toolkit, which could be targets of epigenetic alterations, especially aberrations in DNA methylation . This perspective highlights the intricate link between DNA methylation and Ca2+ signaling in somatic cells by bringing forward evidence from cancer research, further warranting an investigation into this intriguing relationship in oocytes. From a therapeutic standpoint, if our hypothesis is proven to be correct, this will explain the cause of TFF in idiopathic cases and will open doors for novel therapeutic targets.