mechanism-shu-mu-brain-kidney-acupoint-treating-oligoasthenospermia

Mechanism of Shu-Mu Brain-Kidney Acupoint in Treating Oligoasthenospermia in Rats <em>via</em> the Hypothalamic-Pituitary-Testicular Axis

Oligoasthenospermia is a common cause of male infertility. The hypothalamic-pituitary-testicular (HPT) axis regulates gonadal differentiation and ...

Ningxia medical university

Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education

Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease

In this study, we analyzed the differential expression and key signaling pathways of proteins in the skin of guinea pigs with melanin deposition caused by two different modeling methods by utilizing proteomics techniques.

Proteomic Analysis of Two Different Methods to Induce Skin Melanin Deposition Models in Guinea Pigs.

Excessive DNA damage triggers various types of programmed cell death (PCD), yet the regulatory mechanism of DNA damage-induced cell death is not fully understood. Here, we report that PANoptosis, a coordinated PCD pathway, including pyroptosis, apoptosis and necroptosis, is activated by DNA damage. The Z-DNA binding protein 1 (ZBP1) is the apical sensor of PANoptosis and essential for PANoptosome assembly in response to DNA damage. We find endogenous retroviruses (ERVs) are activated by DNA damage and act as ligands for ZBP1 to trigger PANoptosis. By using ZBP1 knock-out and knock-in mice disrupting ZBP1 nucleic acid-binding activity, we demonstrate that ZBP1-mediated PANoptosis contributes to the toxic effects of chemotherapeutic drugs, which is dependent on ZBP1 nucleic acid-binding activity. We found that ZBP1 expression is downregulated in tumor tissue. Furthermore, in colorectal cancer patients, dsRNA is induced by chemotherapy and sensed by ZBP1 in normal colonic tissues, suggesting ZBP1-mediated PANoptosis is activated by chemotherapy in normal tissues. Our findings indicate that ZBP1-mediated PANoptosis is activated by DNA damage and contributes to the toxic side effects of DNA-damage-based chemotherapy. These data suggest that ZBP1 could be a promising therapeutic target to alleviate chemotherapy-related side effects.

Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy.

Male infertility is most commonly caused by oligozoospermia, and its pathogenesis is still poorly understood at the molecular level. This study used RNA sequencing (RNA-Seq) technology to identify candidate genes and regulatory pathways that regulate semen quality in the hypothalamic, pituitary, and testicular tissues of healthy rats and Adenine-induced oligozoospermia model rats. Semen quality testing and histological analysis of testicular tissues were performed on both groups of rats. We identified 627, 692, and 437 differentially expressed genes in the hypothalamus, pituitary gland, and testes, respectively. Functional analysis indicates that "neuronal projections," "positive regulation of hormone biosynthetic process," and "neuroactive ligand-receptor interaction pathways" are closely related to the hypothalamic-pituitary-testicular (HPT) axis hormone regulation and sperm production. Seven genes (Pomc, Rxfp1, Tac1, Npy, Insl3, Hsd3b3, Lhcgr) have been identified as key candidate genes responsible for regulating sperm quality within the HPT axis, potentially affecting rat reproductive function by influencing testicular development and testosterone secretion. These data provide a theoretical basis for further understanding the molecular mechanisms of reproductive performance in a rat model of oligoasthenozoospermia.

Transcriptomic analysis of the HPT axis in a model of oligoasthenozoospermia induced by Adenine in rats.

The transcriptomic analysis was used to explore the effect of electroacupuncture therapy with distant-approximal acupoints based on the hypothalamic-pituitary-testicular (HPT) on gene expression patterns and pathways in oligoasthenospermia (OAT) rats. In this study, the rat model of OAT after intragastric administration of adenine was selected as the research object, and randomly divided into a blank group (C), a model group (M), and a electroacupuncture therapy with distant-approximal acupoints group (D). After electroacupuncture intervention, the epididymal sperm quality and serum sex hormone levels of rats was detected and three tissue samples of HPT axis were taken, and differentially expressed genes (DEGs) were screened by transcriptome sequencing technology. GO functional annotation and KEGG pathway enrichment analysis were performed on the DEGs. The oxidative stress related indicators in serum and HPT axis were also detected to verify the transcriptomic analysis results. Compared with group C, group M rats showed a decrease in sperm count (p < 0.001), sperm survival rate (p < 0.001), and sperm motility rate (p < 0.001); the serum levels of GnRH in the group M rats decreased (p < 0.001), FSH increased (p < 0.001), LH increased (p < 0.001), and T decreased (p < 0.001). Compared with group M, group D rats showed an increase in sperm count (p < 0.01), sperm survival rate (p < 0.001), sperm motility rate (p < 0.001), an increase in GnRH levels (p < 0.001), a decrease in FSH levels (p < 0.01), a decrease in LH levels (p < 0.001), and an increase in T levels (p < 0.001). In bioinformatics analysis, compared with group M, we identified 1656, 518, 530 DEGs in the hypothalamus, pituitary, and testis in group D, respectively. Combining the go and KEGG analysis results, three oxidative stress signaling pathways that may be related to electroacupuncture intervention in OAT rats were screened. It mainly involves the glutamatergic synaptic pathway, the MAPK signaling pathway and the glutathione metabolism pathway. Six key genes (Gng12、Grin1、Gng7、Jun、Nf1 and Gstp1) were identified as key candidate genes regulating epididymal sperm quality on the HPT axis, which may affect the reproductive function of rats by affecting the process of oxidative stress in vivo. No matter in serum or in three tissues of HPT axis, GPX4 level in group M was decreased compared with Group K (p < 0.0001), while GPX4 level in group D was increased compared with group M (p < 0.0001). This study found that the effect of electroacupuncture therapy with distant-approximal acupoints based on the HPT axis in rats with OAT is related to the process of oxidative stress. And the main genes involved in the oxidative stress pathway were identified, which provided directions and ideas for subsequent research. But these results are only the preliminary results of transcriptomics, and relevant experiments need to be designed to further verify the mechanism of electroacupuncture therapy in rats with OAT.

Assessment of Electroacupuncture Therapy with Distant-Approximal Acupoints Based on the HPT Axis in Rats with Oligoasthenospermia Through Transcriptomic Analysis.

Correction: Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy.

Article	Year
Proteomic Analysis of Two Different Methods to Induce Skin Melanin Deposition Models in Guinea Pigs. Clinical, cosmetic and investigational dermatology\| PubMed ID: 37663883	2023
Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy. Cell death & disease\| PubMed ID: 39465258	2024
Transcriptomic analysis of the HPT axis in a model of oligoasthenozoospermia induced by Adenine in rats. Experimental and molecular pathology\| PubMed ID: 39700678	2025
Assessment of Electroacupuncture Therapy with Distant-Approximal Acupoints Based on the HPT Axis in Rats with Oligoasthenospermia Through Transcriptomic Analysis. Reproductive sciences (Thousand Oaks, Calif.)\| PubMed ID: 40016484	2025
Correction: Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy. Cell death & disease\| PubMed ID: 40394006	2025

Kaiying Li

Biography

JoVE Journal Publications

Other Publications