Editorial: Current insights in sperm motility and male fertility

Abstract

Reflecting rigorous editorial standards and peer review, a total of 27 original manuscripts were submitted to this Topic, of which 6 high-quality papers were ultimately accepted (representing an acceptance rate of 22%).The six accepted manuscripts collectively cover a broad spectrum of basic, translational, and clinical reproductive science. The collection includes with two clinical studies offering direct implications for sperm motility management. The first investigates a novel molecular post-translational pathway: the human sperm lactylome in varicocele associated asthenozoospermia. The second clinical study addresses the diagnostic and therapeutic utility of seminal plasma Osteopontin for sperm motility. Moving from clinical pathology to molecular pathophysiology, the collection builds upon the established role of oxidative stress in male factor infertility and elucidating the role of the gut microbiota-testis axis in sperm motility. The collection also includes a review on adverse gonadotoxic effects of imatinib therapy, a crucial area of inquiry given that chronic myeloid leukemia frequently presents in men of reproductive age who wish to preserve their fertility potential. Finally, the collection concludes with a biophysical, functional study that translates laboratory kinetics directly into actionable protocols for low-complexity ART procedures.Cao et al. characterize the human sperm lactylome, demonstrating that a disrupted lactate-lactylation axis in varicocele-associated asthenozoospermia. Analyzing paired pre-and post-varicocelectomy samples, the authors identified that decreased intracellular lactate levels directly correlate with global midpiece and flagellar hypolactylation. Quantitative proteomic profiling revealed 133 differentially lactylated sites on proteins essential for sperm motility, mitochondrial energy production, and axonemal structural organization, many of which partially recovered following surgical repair. By uncovering this novel metabolite-driven posttranslational modification, the study provides a vital mechanistic foundation for understanding varicocele-induced sperm dysfunction and highlights prospective therapeutic targets.Zhang et al. assess the diagnostic and functional significance of seminal plasma osteopontin (OPN) in infertile men presenting with asthenozoospermia. A significant decreased in OPN concentrations in the infertile cohort was observed, establishing seminal OPN as a robust biomarker. Furthermore, in-vitro supplementation with recombinant OPN induced a clear dose-dependent improvement in progressive motility, total motility, and specific kinematic parameters (VCL, VSL, VAP), suggesting its promising utility as a therapeutic additive in ART media during sperm preparation.Hu et al. investigate the gut-testis axis, demonstrating that Morinda officinalis oligosaccharides (MOS) effectively rescue sperm motility and reduce morphological abnormalities in a mouse model of asthenozoospermia. Mechanistically, oral administration of MOS successfully remodels the gut microbiota by selectively increasing the abundance of short-chain fatty acidproducing bacteria, notably the genus Anaerococcus. Fecal microbiota transplantation confirmed that Anaerococcus enrichment directly drives testicular protection, highlighting the therapeutic potential of targeting the gut microbiome in male factor infertility.Wei et al. examine the multifaceted impact of oxidative stress in patients with asthenozoospermia undergoing in-vitro fertilization (IVF). The sperm DFI, ROS levels, and MMP are indicators of sperm genetic stability, oxidative stress status, and energy metabolism level, respectively. Measuring these parameters holds significant guiding value for a deeper understanding of sperm function including sperm motility. Crucially, the study shows that while individual evaluations of DFI or MMP yield only moderate predictive value for pregnancy, combining DFI, and MMP assessments into a unified functional panel significantly enhances the predictive accuracy for fertilization rates, blastocyst development, and clinical pregnancy outcomes in ART settings, offering clinicians a robust diagnostic tool.Ji et al. present a comprehensive scoping review evaluating imatinib-induced testicular toxicity and male fertility impairment. The authors detail how targeted tyrosine kinase inhibition (specifically blocking c-KIT and PDGFR signaling) triggers downstream PI3K/AKT-mediated germ cell apoptosis, meiotic arrest, and structural flagellar defects. Experimental and clinical data identified neonatal and prepubertal periods as particularly vulnerable developmental windows, during which exposure is frequently associated with partially irreversible impairment of spermatogenesis and endocrine function and hence fertility.Mendeluk et al. establish a novel, standardized diagnostic protocol utilizing 10-μm counting chambers and Computer-Assisted Sperm Analysis (CASA) to quantify Transition Hyperactivated (TH) sperm motility as a functional biomarker for male fertility. Evaluation of semen samples revealed that baseline TH levels in ejaculates (%THE) were significantly higher in fertile men compared to infertile patients. The authors identified a threshold of %THE > 9% as predictive of superior sperm recovery following density gradient or swim-up processing. Additionally, in-vitro non-genomic L-thyroxine (T4) treatment significantly boosted TH motility and total gamete recovery in borderline samples, enabling previously sub-optimal ejaculates to successfully meet the threshold required for Intrauterine Insemination (IUI).While the contributions compiled in this Research Topic significantly advance our current understanding of sperm physiology and clinical diagnostics, several core goals originally set forth in our call for papers remain unfulfilled, defining clear priorities for future research in the field:International Consensus and Analytical Standardization: Achieving a globally accepted consensus on the standardized assessment of sperm motility and kinetic classification (velocity and linearity) remains an urgent need. Future initiatives must prioritize multi-center collaborative trials aimed at standardizing CASA hardware settings, chamber depths, frame acquisition rates, and mathematical algorithms across international laboratories to guarantee inter-center reproducibility.Standardization of Capacitation and Hyperactivation Protocols: While progress has been made in baseline kinetic profiling, laboratory methodologies for standardizing hyperactivated motility under physiological capacitation conditions require rigorous refinement. Establishing standardized protocols for inducing, measuring, and interpreting hyperactivation in vitro will be essential for integrating functional sperm testing into routine clinical practice.Translational Molecular and Biophysical Insights: A deeper exploration of the structural, mechanical, and bioenergetic signaling principles governing flagellar motion is needed. Bridging basic biophysical research-such as post-translational lactylation profiling and microfluidic motility selection-with clinical reproductive medicine will be vital to developing targeted pharmacological therapies for severe asthenozoospermia.Gabriela R. Mendeluk and Nafisa H. Balasinor