Interplay mechanisms between progesterone and endocannabinoid receptors in regulating bull sperm capacitation and acrosome reaction

Abstract

After ejaculation, sperm show a limited capacity for transcription and translation. In the oviduct, most of the signalling in sperm is nongenomic and is mediated through membrane receptors. Studies have shown that the cation channel of sperm (CatSper), cAMP, cGMP, protein kinases, and tyrosine phosphorylation are involved in the nongenomic signalling of progesterone (P4) in sperm. However, it is not known whether there is an interplay between P4 and cannabinoid receptors 1 and 2 (CB1 and CB2), transient receptor potential vanilloid 1 (TRPV1), CatSper channels, cAMP, inositol trisphosphate receptor (IP3R), and mitogen-activated protein kinase (MAPK); these potential regulators are involved in the regulation of capacitation and the acrosome reaction. In the present study, selective blockers of CB1, CB2, TRPV1, CatSper channels, cAMP, protein kinase A (PKA), IP3R, and MAPK were used to identify their involvement in P4-mediated bull sperm capacitation and the acrosome reaction. Selective blocking of any one of the molecules caused a significant reduction in P4 signalling (p < 0.05). Interestingly, blocking these molecules in combination followed by treatment with P4 resulted in the complete absence of capacitation and the acrosome reaction. Blocking a single receptor was not able to eliminate the P4-induced capacitation and the acrosome reaction. In addition to the CB1 and CB2 receptors, there may be other signalling pathways that mediate P4 signalling. In conclusion, P4 signalling exhibited interplay with the cannabinoid receptors. The regulation of sperm capacitation and the acrosome reaction also involved cAMP, PKA, L-type and T-type calcium channels, TRPV1, inositol trisphosphate, and MAPK.

Alkaline Dilution Alters Sperm Motility in Dairy Goat by Affecting sAC/cAMP/PKA Pathway Activity

“…Once free, the catalytic subunits remain active to phosphorylate a wide variety of substrates on Ser/Thr residues [ 53 ]. PKA is responsible for the phosphorylation cascades that activate the different ion channels implicated in cytoplasm alkalinization [ 54 ], leading to increased membrane fluidity following cholesterol efflux, membrane hyperpolarization, and phosphorylation of several flagellar proteins, including axonemal and peri-axonemal proteins, and others involved in metabolism. PKA regulates many functional processes occurring in the germ cells: motility, capacitation, biochemical changes at the acrosomal and plasma membrane, the acrosome reaction, and fertilization [ 45 ].…”

Identification and Validation of Yak (Bos grunniens) Frozen–Thawed Sperm Proteins Associated with Capacitation and the Acrosome Reaction

“…GSEA analyses revealed significant MAPK and cAMP pathway gene set downregulation in the AR samples relative to the FTH sperm samples, in line with prior data indicating that these MAPK and cAMP pathways can regulate capacitation and AR induction in sperm. 127 Parkinson's disease protein 7 (PARK7) is an essential regulator of sperm motility, oxidative stress responses, mitochondrial function, and fertility. 128−130 PARK7, also known as DJ-1, localizes to the head, anterior midpiece, and principal piece of human sperm, 131 while it has also been observed on the surface of the equatorial segment in sperm from mammalian species including sheep, horses, rats, hamsters, rabbits, and cattle.…”

Quantitative phosphoproteomics analyses reveal the regulatory mechanisms related to frozen-thawed sperm capacitation and acrosome reaction in yak (Bos grunniens)

“…The two motifs “RxxSP” and “TP” can be recognized by PKA, MAPK and CDK ( Wang et al, 2019 ; Zhang et al, 2021 ). It is well-known that PKA plays a central role in regulating mammalian sperm capacitation and AR ( Baro Graf et al, 2020 ), and MAPK is also another kinase that regulates sperm capacitation and AR ( Mahajan et al, 2022 ). The phosphoproteomics results in this study showed that some key proteins involved in reproduction, such as ODF2, PPKAR1A, CABYR, AKAP3, AKAP4, and PARK7 were phosphorylated on the motif of PKG, PKA, AKT, PKC, and AMPK, respectively, indicating that these proteins are potential targets for response kinases ( Huang et al, 2018 ; Xu et al, 2021 ).…”