BioMed Research International

Review Article

Calcium Influx and Male Fertility in the Context of the Sperm Proteome: An Update

Table 1

Summary of published works on ion channels and physiological stimuli of mammalian spermatozoa that regulate the Ca²⁺ influx mechanism.


Name of channel/stimuli	Localization on spermatozoa/availability	Role in Ca²⁺ influx	Role in sperm physiology	Effect of knocking down/absence	Reference

CatSper CatSper 1 CatSper 2 CatSper 3 CatSper 4 CatSperβ CatSperγ	Principal piece	Regulates Ca²⁺ influx	Ca²⁺ uptake, hyperactivated motility	Sterile	Barratt and Publicover, [19]; Qi et al. [20]

Hv1	Principal piece	Intracellular pH, alkalization thus stimulate Ca²⁺ influx	Extrudes protons from flagella, alkalization	Fertile	Lishko et al. [21], Lishko et al. [22]

	Midpiece	Selectively transports the Ca²⁺	Ca²⁺ influx, alkalization	Fertile	Navarro et al. [23]

TRPC	Principal piece, midpiece	Stimulates opening of CatSper	Ca²⁺ influx, cell depolarization	Fertile	Gees et al. [24], Castellano et al. [25]

CNG	Sperm flagellum, head	Stimulates opening of CatSper via cAMP/cGMP	Ca²⁺ influx	Fertile	Biel and Michalakis [26]

HCN	Flagellum	Depolarization and opening of CatSper	Ca²⁺ influx	Fertile	Wiesner et al. [27]

SOC	Plasma membrane	ZP-induced Ca²⁺ influx	Sperm chemotactic	Subfertile	Yoshida et al. [28]

sACY cAMP/cGMP	Intracellular space and cell membrane	Activates CatSper, CNG, and HCN to regulate Ca²⁺ influx	Ca²⁺ influx, alkalization	Sterile	Esposito et al. [29], Hess et al. [30]

GPCR(s)	Principal piece, midpiece	ZP-induced Ca²⁺ influx increases in [Ca²⁺]_i	Maintains fertilization	Subfertile	Fukami et al. [31] Fukami et al. [32]

PLCδ	Acrosome	ZP induced increases in [Ca²⁺]_i	Ca²⁺ influx	Subfertile	Fukami et al. [32]

Ca²⁺-ATPase pump	Principal piece	Intracellular pH and alkalization	Ca²⁺ influx, capacitation	Motility loss results in infertility	Wennemuth et al. [33]

ZP glycoproteins	Follicle	Induced Ca²⁺-dependent increase in [Ca²⁺]_i	Hyperactivation, capacitation	Delayed capacitation	Florman [34], Florman et al. [35]

Endocrine disruptor (p,p′-DDE)	Female reproductive tract	Activates CatSper	Ca²⁺ influx	Motility loss, delayed capacitation	Tavares et al. [36]

BSA	Extracellular space	Similar to ZP glycoprotein	In vitro capacitation	Motility loss, subfertility	Xia and Ren [37] Bailey and Storey [38]

Oviductal and follicular fluid	Extracellular space (in vivo)	Ca²⁺-dependent increase in [Ca²⁺]_i in sperm	Ca²⁺ influx	Motility loss delayed capacitation	Xia and Ren [37]

Hv1: voltage-gated proton channel; : ATP-gated channel; TRPC: transient receptor potential channels; CNG: cyclic nucleotide-gated ion channel; HCN: hyperpolarization-activated cyclic nucleotide-gated channel; SOC: store-operated Ca²⁺ channel; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; sACY: soluble adenylyl cyclase; GPCR: glutamate receptor family class-C; PLCδ: phospholipase C zeta; ZP: zona pellucida; p,p′-DDE: p,p^'-dichlorodiphenyldichloroethylene; BSA: bovine serum albumin.