# The involvement of TRPV1 in the apoptosis of spermatogenic cells in the testis of mice with cryptorchidism

**Authors:** Yanqiu Zhao, Jinhua Wei, Pang Cheng, Junxian Ma, Bo Liu, Mingxiang Xiong, Ting Gao, Jingqi Yao, Tianchen Sun, Zhen Li

PMC · DOI: 10.1038/s41420-025-02447-3 · Cell Death Discovery · 2025-04-03

## TL;DR

This study shows that TRPV1 contributes to spermatogenic cell death in mice with cryptorchidism, a condition linked to infertility and testicular cancer.

## Contribution

The study reveals a novel role of TRPV1 in promoting spermatocyte apoptosis in cryptorchidism through regulation of apoptosis-related genes.

## Key findings

- TRPV1 expression increases in the testes of cryptorchid mice.
- Trpv1−/− mice show reduced spermatogenic cell apoptosis and reproductive damage.
- Apoptosis-related genes are downregulated in Trpv1−/− cryptorchid mice.

## Abstract

Cryptorchidism is associated with an increased risk of male infertility and testicular cancer. Persistent exposure to high temperature in cryptorchidism can lead to the apoptosis of spermatogenic cells. Transient receptor potential vanilloid 1 (TRPV1), a thermosensitive cation channel, has been found to have differential effects on various apoptosis processes. However, whether TRPV1 is involved in spermatogenic cell apoptosis induced by cryptorchidism remains unclear. Herein, we first observed the expression pattern of TRPV1 in the testes of mice with experimental cryptorchidism, and then investigated the role and mechanism of TRPV1 in spermatogenic cell apoptosis by using Trpv1−/− mice. The results showed that TRPV1 was highly expressed on the membrane of spermatocytes in mouse testis, and the expression increased significantly in the testis of mice with experimental cryptorchidism. After the operation, Trpv1−/− mice exhibited less reproductive damage and fewer spermatogenic cell apoptosis compared to the wild-type (WT) mice. Transcriptome sequencing revealed that the expression of apoptosis-related genes (Capn1, Capn2, Bax, Aifm1, Caspase 3, Map3k5, Itpr1 and Fas) was down-regulated in spermatocytes of cryptorchid Trpv1−/− mice. Our results suggest that TRPV1 promotes the apoptosis of spermatocytes in cryptorchid mice by regulating the expression of apoptosis-related genes.

## Linked entities

- **Genes:** TRPV1 (transient receptor potential cation channel subfamily V member 1) [NCBI Gene 7442], CAPN1 (calpain 1) [NCBI Gene 823], CAPN2 (calpain 2) [NCBI Gene 824], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], AIFM1 (apoptosis inducing factor mitochondria associated 1) [NCBI Gene 9131], Casp3 (caspase 3) [NCBI Gene 12367], MAP3K5 (mitogen-activated protein kinase kinase kinase 5) [NCBI Gene 4217], ITPR1 (inositol 1,4,5-trisphosphate receptor type 1) [NCBI Gene 3708], FAS (Fas cell surface death receptor) [NCBI Gene 355]
- **Diseases:** cryptorchidism (MONDO:0009047), testicular cancer (MONDO:0003510)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Aifm1 (apoptosis-inducing factor, mitochondrion-associated 1) [NCBI Gene 26926] {aka AIF, AIFsh2, Hq, Pdcd8}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Capn1 (calpain 1) [NCBI Gene 12333] {aka Capa-1, Capa1, mu-calpin}, Capn2 (calpain 2) [NCBI Gene 12334] {aka CALP80, Capa-2, Capa2, m-calpain, m-calpin}, Itpr1 (inositol 1,4,5-trisphosphate receptor 1) [NCBI Gene 16438] {aka D6Pas2, Gm10429, IP3R 1, IP3R1, InsP3R, Ip3r}, Map3k5 (mitogen-activated protein kinase kinase kinase 5) [NCBI Gene 26408] {aka 7420452D20Rik, ASK, ASK1, MAPKKK5, Mekk5}, Trpv1 (transient receptor potential cation channel, subfamily V, member 1) [NCBI Gene 193034] {aka OTRPC1, TRPV1alpha, TRPV1beta, VR-1, Vr1}
- **Diseases:** Cryptorchidism (MESH:D003456), testicular cancer (MESH:D013736), male infertility (MESH:D007248), reproductive damage (MESH:D060737)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC11968804/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11968804/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC11968804/full.md

---
Source: https://tomesphere.com/paper/PMC11968804