Boar spermatozoa successfully predict mitochondrial modes of toxicity: Implications for drug toxicity testing and the 3R principles

The mu (μ) and delta (δ) opioid receptors modulate boar sperm motility

“…Finally, boar spermatozoa can be used to detect drug‐induced toxicity using kinematics as an indicator in a simple motility assay (Vicente‐Carrillo et al, ) as well as for mapping changes in CatSper receptors under capacitation conditions (unpublished). The current findings that μ‐ and δ‐opioid receptors on ejaculated boar spermatozoa regulate motility further highlight the utility of such assays when exploring opiates and their interaction with membrane receptors as well as for other types of receptors.…”

“…The algorithm calculates the number of fluctuations in each pixel by correlation function, which is used to calculate the speed (velocity) distribution. This system runs in high throughput mode (usually four fields per minute), analyzing >2,000 spermatozoa/field, and has been validated for several species, including porcine (Tejerina et al, , ; Rodriguez‐Martinez et al ; Johannisson et al, ; Siqueira et al, ; Vicente‐Carrillo et al, ).…”

“…Boar spermatozoa are valuable for pharmacological and toxicological in vitro testing (Vicente‐Carrillo et al, ). This study was undertaken to address (i) the presence and distribution of µ‐, δ‐, and κ‐opioid receptors in these gametes and (ii) their relation to in vitro sperm kinematics, sperm viability, mitochondrial integrity, and early membrane destabilization using specific agonists (morphine [µ]; [D‐Pen 2,5]‐enkephanile (DPDPE) [δ]; and U 50488 [κ]) and antagonists (naloxone [µ]; naltrindole [δ]; and nor ‐binaltrorphimine [κ]).…”

The Usefulness of Sperm Kinematics in Drug‐Induced Toxicity Assessment

“…Considering that mitochondrial‐induced toxicity is the main cause of drug‐induced toxicity, the need for a fast, reliable and animal‐free system for detection of mitochondrial modes of toxicity appears. To this request, the use of sperm kinematics as indirect measurement of drug‐induced mitochondrial toxicity has been suggested .…”

“…Spermatozoa possess a high capability to adapt to different conditions, and such adaptability is reflected in terms of changes both in their plasma membrane and sperm motility . Changes in sperm plasma membrane and kinematics in response to stimuli can be tracked and quantified via different techniques, what makes possible the use of the sperm capability to adapt to different conditions as an indicator of, for instance, cytotoxicity .…”