Sex differences in lower urinary tract function in mice with or without spinal cord injury

Author:

Hashimoto Mamoru12,Karnup Sergei3,Daugherty Stephanie L.3,Cho Kang Jun14,Banno Eri2,Shimizu Nobutaka5,Fujita Kazutoshi2,Hirayama Akihide6,Uemura Hirotsugu2,de Groat William C.3,Beckel Jonathan M.3ORCID,Yoshimura Naoki13ORCID

Affiliation:

1. Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

2. Department of Urology Kindai University Faculty of Medicine Osaka‐Sayama Japan

3. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

4. Department of Urology College of Medicine, The Catholic University of Korea Seoul Republic of Korea

5. Pelvic Floor Center, Kochi Medical School Kochi University Nankoku Japan

6. Department of Urology Kindai University Nara Hospital Ikoma Japan

Abstract

AbstractObjectivesWe examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI).MethodsSCI was induced by Th8−9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6‐S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme‐linked immunosorbent assay.ResultsSex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice.ConclusionsWe demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6‐S1 DRG and NGF in the bladder could be involved in SCI‐induced lower urinary tract dysfunction in both sexes of mice.

Publisher

Wiley

Subject

Urology,Neurology (clinical)

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