PIEZO2 and perineal mechanosensation are essential for sexual function

Ruby M. Lam; Lars J. von Buchholtz; Melanie Falgairolle; Jennifer Osborne; Eleni Frangos; M. Rocio Servin-Vences; Maximilian Nagel; Minh Q. Nguyen; Monessha Jayabalan; Dimah Saade; Ardem Patapoutian; Carsten G. Bönnemann; Nicholas J.P. Ryba; Alexander T. Chesler

doi:10.1126/science.adg0144

PIEZO2 and perineal mechanosensation are essential for sexual function

Ruby M. Lam, Lars J. von Buchholtz, Melanie Falgairolle, Jennifer Osborne, Eleni Frangos, M. Rocio Servin-Vences, Maximilian Nagel, Minh Q. Nguyen, Monessha Jayabalan, Dimah Saade, Ardem Patapoutian, Carsten G. Bönnemann, Nicholas J.P. Ryba, Alexander T. Chesler^*

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. 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 (piezo-type mechanosensitive ion channel component 2) is necessary for behavioral sensitivity to perineal touch. 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 help explain how perineal mechanoreceptors detect the gentlest of stimuli and trigger physiologically important sexual responses, thus providing a platform for exploring the sensory basis of sexual pleasure and its relationship to affective touch.

Original language	English (US)
Pages (from-to)	906-910
Number of pages	5
Journal	Science
Volume	381
Issue number	6660
DOIs	https://doi.org/10.1126/science.adg0144
State	Published - Aug 25 2023

Funding

We thank T. Delong, M. Singh, and M. Bradson for distributing questionnaires to human subjects and collating clinical notes; members of the clinical staff at NCCIH and Bönnemann groups for support in arranging human studies; and M. Szczot, N. Ghitani, D. Macdonald, and R. Hardy for input and expertise with animal experiments. Hormone analysis was carried out by the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core. This work was supported by the National Institutes of Health, NCCIH Z01-ZIAAT000028 (to A.T.C.); National Institutes of Health, NIDCR Z01-ZIADE000561 (to N.J.P.R.); National Institutes of Health, NINDS Z01-ZIANS003129 (to C.G.B.); and the Howard Hughes Medical Institute (to A.P.)

ASJC Scopus subject areas

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title = "PIEZO2 and perineal mechanosensation are essential for sexual function",

abstract = "Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. 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 (piezo-type mechanosensitive ion channel component 2) is necessary for behavioral sensitivity to perineal touch. 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 help explain how perineal mechanoreceptors detect the gentlest of stimuli and trigger physiologically important sexual responses, thus providing a platform for exploring the sensory basis of sexual pleasure and its relationship to affective touch.",

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AU - Frangos, Eleni

AU - Servin-Vences, M. Rocio

AU - Nagel, Maximilian

AU - Nguyen, Minh Q.

AU - Jayabalan, Monessha

AU - Saade, Dimah

AU - Patapoutian, Ardem

AU - Bönnemann, Carsten G.

AU - Ryba, Nicholas J.P.

AU - Chesler, Alexander T.

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PIEZO2 and perineal mechanosensation are essential for sexual function

Abstract

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