Calcium signaling in oocyte quality and functionality and its application

Abstract

Calcium (Ca²⁺) is a second messenger for many signal pathways, and changes in intracellular Ca²⁺ concentration ([Ca²⁺]i) are an important signaling mechanism in the oocyte maturation, activation, fertilization, function regulation of granulosa and cumulus cells and offspring development. Ca²⁺ oscillations occur during oocyte maturation and fertilization, which are maintained by Ca²⁺ stores and extracellular Ca²⁺ ([Ca²⁺]e). Abnormalities in Ca²⁺ signaling can affect the release of the first polar body, the first meiotic division, and chromosome and spindle morphology. Well-studied aspects of Ca²⁺ signaling in the oocyte are oocyte activation and fertilization. Oocyte activation, driven by sperm-specific phospholipase PLCζ, is initiated by concerted intracellular patterns of Ca²⁺ release, termed Ca²⁺ oscillations. Ca²⁺ oscillations persist for a long time during fertilization and are coordinately engaged by a variety of Ca²⁺ channels, pumps, regulatory proteins and their partners. Calcium signaling also regulates granulosa and cumulus cells' function, which further affects oocyte maturation and fertilization outcome. Clinically, there are several physical and chemical options for treating fertilization failure through oocyte activation. Additionally, various exogenous compounds or drugs can cause ovarian dysfunction and female infertility by inducing abnormal Ca²⁺ signaling or Ca²⁺ dyshomeostasis in oocytes and granulosa cells. Therefore, the reproductive health risks caused by adverse stresses should arouse our attention. This review will systematically summarize the latest research progress on the aforementioned aspects and propose further research directions on calcium signaling in female reproduction.

Keywords: Ca2+ oscillations; calcium; female fertility; fertilization; oocyte activation; oocyte maturation.