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Wu Zi Yan Zong Wan (WZYZW) is a well-known Traditional Chinese Medicine formula used to treat low sperm quality, although its underlying therapeutic mechanism remains incompletely elucidated. This study aimed to elucidate the therapeutic mechanism of WZYZW for low sperm quality in breeding boars and to evaluate its potential for extending their reproductive lifespan. Boars with low sperm quality were pre-screened using the CASA system and WZYZW was added to the diet as an intervention. Sperm viability, ejaculate volume, sperm density, FSH, LH, testosterone T, Ca2+, Zn2+, T-AOC, GSH-Px, SOD and Giemsa staining were evaluated after 8 weeks to evaluate the therapeutic effect of WZYZW on boars with low sperm quality. Furthermore, an investigation was conducted into the potential mechanisms of WZYZW for treating low sperm quality in boars. This investigation utilized quantitative polymerase chain reaction (qPCR), 16S RNA sequencing, and thermal correlation analysis. WZYZW significantly restored sperm motility, ejaculate volume, and sperm density in boars with initial poor semen quality. The treatment also effectively reduced sperm deformities and increased the levels of FSH, testosterone (T), fructose, Ca2+, Zn2+, total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD). At the molecular level, WZYZW altered chromatin structure and the expression of adhesion protein family genes, potentially via the cAMP-AKT pathway. Furthermore, 16S rRNA sequencing revealed that WZYZW significantly suppressed the relative abundance of the phyla Tenericutes and Proteobacteria. Correlation analysis suggested that the abundance of these gut microbiota taxa may be associated with signaling pathways regulating cell growth and death. Our results demonstrate that WZYZW is a promising therapeutic agent for low sperm quality in boars, which acts by modulating spermatogenesis-related gene expression and reshaping the gut microbiota, thereby extending the reproductive lifespan of breeding boars.

Wu-Zi-Yan-Zong (WZYZ) formula is a traditional Chinese botanical drug that has been used to treat male infertility. This meta-analysis aims to evaluate its effectiveness of the WZYZ formula as an adjuvant therapy for treating abnormal sperm parameters associated with male infertility. A comprehensive literature search was conducted using PubMed, Embase, Cochrane Library, Web of Science, SinoMed, Wanfang, and CNKI databases until December 12, 2024 to identify randomized controlled trials (RCTs) that assessed the effectiveness of the WZYZ formula as an adjuvant therapy for treating abnormal sperm parameters associated in men with infertility. For dichotomous data, the pooled results were summarized as risk ratio (RR) with 95% confidence intervals (CI), while continuous data were expressed as pooled weighted mean difference (WMD) with 95% CI. A total of 11 RCTs involving 951 men were identified. The pooled results showed that the WZYZ formula, when combined with control treatment, significantly improved the pregnancy rate of female partners (RR 1.68; 95% CI 1.34-2.11), semen volume (WMD 0.58 mL; 95% CI 0.28-0.89), sperm concentration (WMD 6.87 × 10 /mL; 95%CI 4.24-9.51), total sperm motility (WMD 15.55%; 95% CI 10.38-20.72), forward grade (a) sperm motility (WMD 5.44%; 95% CI 1.86-9.01), forward grade (a + b) sperm motility (WMD 7.14%; 95% CI 4.04-10.23), abnormal sperm morphology (WMD -10.38%; 95% CI -15.72 to -5.03), and activity of the acrosome enzyme (WMD 8.02 × 10  μIU; 95% CI 3.58-12.46. Adjuvant treatment with WZYZ formula significantly improves the pregnancy rate of female partners by improving several semen parameters in infertile men with abnormal sperm parameters. However, further well-designed RCTs with larger sample sizes are necessary to definitively determine the efficacy and safety of the WZYZ formula in treating abnormal sperm parameters associated with male infertility. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024629510.