Despite the potential importance of genital mechanosensation for sexual reproduction little is known about how perineal touch influences mating. Here we explored how mechanosensation affords exquisite awareness of the genitals and controls reproduction in mice and humans. Using genetic strategies and in vivo functional imaging, we demonstrated that the mechanosensitive ion channel Piezo2 is necessary for behavioral sensitivity to perineal touch. Notably, Piezo2-function is needed for triggering a touch-evoked erection reflex and successful mating in both male and female mice. Humans with complete loss of PIEZO2 function have genital hyposensitivity and experience no direct pleasure from gentle touch or vibration. Together, our results explain how perineal mechanoreceptors detect the gentlest of stimuli and trigger physiologically important sexual responses, providing a platform for exploring the sensory basis of sexual pleasure and its relationship to affective touch.

IVcalcium-final.csv: GCamp calcium imaging data. Each line corresponds to a cell/ROI, columns identify sex, genotype, recording date, ROI name and stimulation area. The remaining numbered columns are the concatenated calcium traces imaged at 5Hz for 200 frames per stimulus. Stimuli are (in order) air puff, brush, pinch, vibration, Von Frey 1.4g, Von Frey 1.0g, Von Frey 0.6g, Von Frey 0.4g, Von Frey 0.16g, Von Frey 0.07g, Von Frey 0.04g,  Von Frey 0.02g, Von Frey 0.008g 

Scn10aCreGCamp-traces.csv: Calcium imaging data from Scn10a-Cre/GCamp mice. Each line corresponds to a cell/ROI, columns are the concatenated calcium traces imaged at 5Hz for 200 frames per stimulus. Stimuli are (in order) air puff, brush, pinch, vibration, Von Frey 1.4g, Von Frey 1.0g, Von Frey 0.6g, Von Frey 0.4g, Von Frey 0.16g, Von Frey 0.07g, Von Frey 0.04g,  Von Frey 0.02g, Von Frey 0.008g 

Ethogram_data.csv: Behavioral data of mating mice manually scored in BORIS software. Each line specifies an event. Experiment column specifies the genotype or experimental condition of the animals. The mouse column provides an id for the individual experiment. Behavior is either groom, mount or sniff/pursuit. All behaviors have a start timestamp (seconds), sniff/pursuit also has a stop timestamp and duration (seconds).

wt_SDimages-20201230.tif: Stack of standard deviation images from a GCamp mouse corresponding to the stimuli air puff, brush, pinch, vibration, Von Frey 1.4g, Von Frey 1.0g, Von Frey 0.6g, Von Frey 0.4g, Von Frey 0.16g, Von Frey 0.07g, Von Frey 0.04g,  Von Frey 0.02g, Von Frey 0.008g. Standard deviation over time for each pixel was calculated in ImageJ. Stack can be opened in ImageJ.

wtROIs-20201230.zip: ROI file for wt_SDimages-20201230.tif; can be imported into ImageJ

Piezo2ko_SDimages-20201127.tif: Stack of standard deviation images from a Piezo2 knockout/GCamp mouse corresponding to the stimuli air puff, brush, pinch, vibration, Von Frey 1.4g, Von Frey 1.0g, Von Frey 0.6g, Von Frey 0.4g, Von Frey 0.16g, Von Frey 0.07g, Von Frey 0.04g,  Von Frey 0.02g, Von Frey 0.008g. Standard deviation over time for each pixel was calculated in ImageJ. Stack can be opened in ImageJ.

Piezo2koROIs-20201127.zip: ROI file for Piezo2ko_SDimages-20201127.tif; can be imported into ImageJ

testicle_weight_ratio.csv: testicle weight divided by body weight for wildtype and conditional Piezo2 ko mice

copulation_plugs.csv: number of matings that resulted in copulation plugs
after 4 hours for various genotypes

estrus_cycles.csv: number of estrus cycles tracked in 25 days 

FSH_levels.csv: Follicle Stimulating Hormone levels (ng/ml) in wt and conditional Piezo2 ko mice

litters.csv: number of litters per breeding pair in 6 months for various genotypes

penile_protrusion.csv: percentage of trials (out of 20) evoking responses in penile protrusion test for individual males of various genotypes/experimental conditions

pinprick_test.csv: percent of trials evoking withdrawal response in pinprick test for various genotypes/sex/experimental conditions

testosterone_levels.csv: testosterone levels (in ng/dl) for wildtype and ko mice

von_Frey_thresholds.csv: minimum von Frey filament strength evoking 50% withdrawal for various genotypes/sex/experimental conditions

von_Frey_responses.csv: each column corresponds to a mouse. Values are percentage of withdrawals (out of 10 trials) for each filament strength.