Identification of a Novel Pyroptosis-related Gene Signature in Human Spermatogenic Dysfunction

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2023 Aug 8

PMID 37553495

Authors

Fan Dong

Yi Ma

Xiang-Feng Chen

Affiliations

Soon will be listed here.

Abstract

Purpose: To reveal the underlying roles that pyroptosis-related genes (PRGs) played in human spermatogenic dysfunction.

Methods: One discovery set and three validation sets were employed to inspect the previously reported 33 PRGs in the human testis with different status of spermatogenesis. PRGs that differentially expressed in all sets were considered as key differentially expressed pyroptosis-related genes (PR-DEGs). The relationships between key PR-DEGs and samples' clinicopathological, therapeutic, and immune patterns were respectively studied. Single-cell RNA sequencing (scRNS-seq) analyses were conducted to show the expression changes and related mechanisms of key PR-DEGs at a single-cell resolution.

Results: CASP4 and GPX4 were identified as two key PR-DEGs. These two genes were significantly dysregulated in spermatogenic dysfunctional samples, but with opposite tendency. CASP4 was negatively correlated with Johnsen scores but positively correlated with follicle-stimulating hormone (FSH) levels (all p < 0.05), while GPX4 exhibited significant positive correlations with Johnsen scores and negative relevance with FSH. For treatments, both molecules showed a prospective value of being predictors for sperm retrieval surgeries. Moreover, CASP4 and GPX4 were potential immunoregulators in the testicular immune microenvironment and showed significant correlations to testicular macrophages and mast cell infiltration. In scRNA-seq analyses, GPX4 was highly expressed in germ cells, which therefore suffered a sharp reduction with the loss of germ cells in spermatogenic dysfunction. On the other hand, CASP4 were basically somatic cell-derived, and the proportion of CASP4-positive Leydig cells significantly increased in disease testes (p = 0.0001).

Conclusion: In all, we revealed two key PRGs of human testes that might be functional in spermatogenic dysfunction.

Citing Articles

Integrative bioinformatics analysis to identify ferroptosis-related genes in non-obstructive azoospermia.

Hong Y, Yuan Q, Wang L, Yang Z, Xu P, Guan X J Assist Reprod Genet. 2024; 41(8):2145-2161.

PMID: 38902567 PMC: 11339017. DOI: 10.1007/s10815-024-03155-0.

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