Heat Sensing Receptor TRPV1 Is a Mediator of Thermotaxis in Human Spermatozoa

Abstract

The molecular bases of sperm thermotaxis, the temperature-oriented cell motility, are currently under investigation. Thermal perception relies on a subclass of the transient receptor potential [TRP] channels, whose member TRPV1 is acknowledged as the heat sensing receptor. Here we investigated the involvement of TRPV1 in human sperm thermotaxis. We obtained semen samples from 16 normozoospermic subjects attending an infertility survey programme, testis biopsies from 6 patients with testicular germ cell cancer and testis fine needle aspirates from 6 patients with obstructive azoospermia undergoing assisted reproductive technologies. Expression of TRPV1 mRNA was assessed by RT-PCR. Protein expression of TRPV1 was determined by western blot, flow cytometry and immunofluorescence. Sperm motility was assessed by Sperm Class Analyser. Acrosome reaction, apoptosis and intracellular-Ca2+ content were assessed by flow cytometry. We found that TRPV1 mRNA and protein were highly expressed in the testis, in both Sertoli cells and germ-line cells. Moreover, compared to no-gradient controls at 31°C or 37°C (Ctrl 31°C and Ctrl 37°C respectively), sperm migration towards a temperature gradient of 31–37°C (T gradient) in non-capacitated conditions selected a higher number of cells (14,9 ± 4,2×106 cells T gradient vs 5,1± 0,3×106 cells Ctrl 31°C and 5,71±0,74×106 cells Ctrl 37°C; P = 0,039). Capacitation amplified the migrating capability towards the T gradient. Sperms migrated towards the T gradient showed enriched levels of both TRPV1 protein and mRNA. In addition, sperm cells were able to migrate toward a gradient of capsaicin, a specific agonist of TRPV1, whilst capsazepine, a specific agonist of TRPV1, blocked this effect. Finally, capsazepine severely blunted migration towards T gradient without abolishing. These results suggest that TRPV1 may represent a facilitating mediator of sperm thermotaxis.

Differential expression and localization of thermosensitive Transient Receptor Potential Vanilloid (TRPV) channels in the mature sperm of white pekin duck (Anas platyrhynchos)

“…In this work, we have observed that TRPV1 is abundant at the neck and tail regions, indicating that TRPV1 could also regulate duck sperm motility. TRPV1 has also been shown to regulate thermotaxis of human sperm and this feature could be conserved in other warm blooded vertebrates like birds too [20]. TRPV1 has also been shown to regulate capacitation of other relevant species, at least for bull and boar sperm [18–19].…”

“…Indeed, heat sensitive TRPV1 has been shown to be functional in fish, mice, boar, bull and human sperm [16–20]. TRPV1 has been shown to be important for progesterone-induced sperm oocyte fusion and TRPV1 activator anandamide can capacitate bull sperm [19, 21].…”

“…TRPV1 has been shown to be important for progesterone-induced sperm oocyte fusion and TRPV1 activator anandamide can capacitate bull sperm [19, 21]. TRPV1 has also been demonstrated to mediate thermotaxis of human sperm [20]. Interestingly TRPV4 has been also shown to mediate thermotaxis in mouse sperm and initiate the initial depolarization event for capacitation in human sperm [22–23].…”

TRPV1 Is Associated with Testicular Apoptosis in Mice

“…34, No. 4, December 2019 and apoptosis De Toni et al, 2016). TRPV1 KO mice have a testis phenotype that is much more vulnerable to cell death induced by oxidative stress stimuli and massive loss of germ cells from seminiferous tubules compared to wild-type (WT) mice Martins et al, 2014).…”

Mechanisms of the sperm guidance, an essential aid for meeting the oocyte

“…The work of De Toni and collaborators (18), is focused on the study of TRPV1 as a molecular modulator of thermotaxis in human spermatozoa. Transient Receptor Potential Cation Channel or Vanilloid Receptor 1 (TRPV1) is a ligand-gated, nonselective cationic channel that is activated by molecules derived from plants, such as capsaicin, and also by stimuli like heat or protons (19).…”