Research Progress on the Microregulatory Mechanisms of Fertilization: A Review

Fine tuning of the fertilization process: Sperm capacitation. Tyinine phosphate protein and ACRBP can initiate AR through the SERCA pump regulating Ca²⁺ concentration in the cell. The combination of IQCF1 and CaM is closely related to the level of tyrosine phosphorylation and AR. When obtaining capacity, the pH of the female reproductive tract is elevated, and K⁺ flows in the sperm, while the extracellular Ca²⁺, HCO³⁻ and Na⁺ induce several cAMP-PKA signal pathways. These pathways activate PKA, so that some sperm proteins are phosphorylated on serine, threonine, especially tyrosine residues causing sperm hyperactivation and AR. HCO³⁻, Ca²⁺, and BSA can cause tyrosine phosphorylation mediating sperm capacitation. However, AR can increase the internal Ca²⁺ of the sperm, the pH is elevated, and Ca²⁺ influx activates the PLC-β. After being stimulated by G-protein, the phosphatidylinositols (PIs) on the membrane are hydrolyzed to produce DAG and phosphoinositide. DAG activates PLA2, which leads to the fusion of the outer acrosomal and plasma membrane. When IP3R is stimulated by intracellular IP3, stored Ca²⁺ is released and directly or indirectly causes influx of exogenous Ca²⁺. Acrosome Ca²⁺ release triggers tyrosine phosphorylation leading to exocytosis. Ca²⁺ induces activation of the PPI signaling pathway and PKC, which in turn activate the opening of Ca²⁺ channels on the sperm membrane to promote the Ca²⁺ influx and AR. Progesterone regulates sperm fertilization via the ABHD2-mediated cAMP-PKA signaling pathway and activates the CatSper of the sperm via ABHD2 to induce Ca²⁺ influx without activating nuclear receptors. After binding with progesterone, ABHD2 is activated to decompose triacylglycerol fats to produce DAG and activate CatSper. Ca²⁺ influx and increased cAMP activate sperm capacitation, hyperactivation, chemotaxis, and AR. Activated ACs increase intracellular cAMP that activates PKA to phosphorylate proteins on serine, threonine and tyrosine residues, thereby regulating sperm capacitation, hyperactivation, chemotaxis, and AR. A23187 binds to Ca²⁺, induces Ca²⁺ influx, and initiates the fusion of sperm plasma membrane and acrosomal outer membrane leading to AR. See the text for details. ABHD2: Abhydrolase domain-containing protein 2; AC: adenylyl cyclase; ACRBP: acrosin binding protein; AR: acrosome reaction; BSA: bovine serum albumin; CaM: calmodulin; cAMP: 3′5′-cyclic adenosine monophosphate; CatSper: cation channel of sperm; DAG: diacylglycerol; IP3: inositol 1,4,5-trisphosphate; IQCF1: IQ motif containing F1; PIs: phosphatidylinositols; P4: progesterone; PIP2: phosphatidylinositol 4,5-bisphosphate; PKA: protein kinase A; PKC: protein kinase C; PLC-β: phospholipase C-β; SERCA: sarco/endoplasmic reticulum Ca²⁺-ATPase.