Proposed parallels between intracellular calcium ion concentration ([Ca²⁺]_i) signals induced by zona pellucida (ZP) in the mouse and progesterone (P) in the human. Shaded areas indicate key events occurring in both pathways. Left-hand pathway represents ZP-induced signaling in murine spermatozoa: an unidentified cation channel (1) and possibly efflux of Cl^- through a glycine receptor (GlyR) (2) provide initial depolarization (shading) leading to activation of a T channel (3). Downstream generation of inositol trisphosphate (IP₃) and depletion of calcium ion (Ca²⁺) stores (shading) cause store-operated channel (SOC) activation (4), which provides the sustained component of the signal. Right-hand pathway represents P-induced signaling in human spermatozoa: activation of an unidentified P-gated channel (i) and possibly efflux of Cl^- through a -aminobutyric acid (GABA_A) receptor (GABA_A R) (ii) provide initial depolarization (shading) leading to activation of a voltage-operated calcium channel (VOCC) (iii). Additionally, the P-gated channel (i) carries the "early" non-VOCC Ca²⁺ influx (iv). Downstream of (iii) or (iv), generation of IP₃ and depletion of Ca²⁺ stores (shading) cause SOC activation (v), which provides the sustained component of the signal.