Abstract
As a second messenger in cellular signal transduction, calcium signaling extensively participates in various physiological activities, including spermatogenesis and the regulation of sperm function. Abnormal calcium signaling is highly correlated with male infertility. Calcium signaling is mainly regulated by both extracellular calcium influx and the release of calcium stores. Inositol 1,4,5-trisphosphate receptor (IP3R) is a widely expressed channel for calcium stores. After being activated by inositol 1,4,5-trisphosphate (IP3) and calcium signaling at a lower concentration, IP3R can regulate the release of Ca2+ from stores into cytoplasm, and eventually trigger downstream events. The closure of the IP3R channel caused by a rise in intracellular calcium signals and the activation of the calcium pump jointly restores the calcium store to a normal level. In this review, we aim to discuss structural features of IP3R channels and the underlying mechanism of IP3R channel-mediated calcium signaling and further focus on the research progress of IP3R expression and function in the male reproductive system. Finally, we propose key directions and strategies for research of IP3R in spermatogenesis and the regulation of sperm function to provide more understanding of the function and mechanism of IP3R channel actions in male reproduction.
Highlights
Ca2+ serves as a second messenger in cellular signal transduction to widely regulate many intracellular events, such as gene expression, synaptic transmission, and cellular death, differentiation and proliferation
Studies have shown that calcium signaling is involved in spermatogenesis, sperm function, and fertilization, essential processes for male reproduction [1]
Abnormal calcium signaling can decrease testosterone levels, which results in abnormal spermatogenesis and even male infertility [5]
Summary
Ca2+ serves as a second messenger in cellular signal transduction to widely regulate many intracellular events, such as gene expression, synaptic transmission, and cellular death, differentiation and proliferation. Studies have shown that calcium signaling is involved in spermatogenesis, sperm function, and fertilization, essential processes for male reproduction [1]. Research on calcium influx during spermatogenesis has been scarce, studies in recent years have analyzed the function and mechanism of the CatSper channel in mature sperm and showed that disrupted calcium influx in sperm was closely related to male infertility. This review will systematically summarize the structural characteristics of the IP3R channel and its expression and function in the male reproductive system, and further discuss future research and strategies for understanding the role of IP3R in the regulation of spermatogenesis and sperm function
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