A Key regulatory protein QRICH2 governing sperm function with profound antioxidant properties, enhancing sperm viability.

Infertility poses a global health and social challenge, affecting approximately 15% of couples at childbearing age, with half of the cases attributed to male factors, wherein genetic factors exert a substantial role. In our prior investigation, we identified loss-of-function variants within the gene encoding glutamine-rich protein 2 (QRICH2) in two consanguineous families, leading to various morphological abnormalities in sperm flagella and male infertility. Moreover, our observations in Qrich2 knockout mice revealed a pronounced reduction in spermatozoa count. However, the underlying mechanism remains elusive, prompting further investigation in the current study. By conducting experiments such as Hematoxylin-eosin (HE) staining, immunofluorescence staining, flow cytometry, and single sperm metabolism analysis on the testes and spermatozoa of Qrich2 knockout mice, we found a strong antioxidant capacity mediated by QRICH2 both in vivo and in vitro. Qrich2 knockout led to elevated levels of ROS, consequently inducing DNA damage in spermatids, which in turn triggered increased autophagy and apoptosis, ultimately causing a significant decrease in spermatozoa count. Incubation with the N-terminal purified protein of QRICH2 exhibited potent strong antioxidant activity at the cell and spermatozoa levels in vitro, thereby enhancing spermatozoa viability and motility. Therefore, QRICH2 plays a crucial role in safeguarding spermatids from excessive ROS-induced damage by augmenting antioxidant capacity, thereby promoting spermatozoa survival and improving motility. Furthermore, the N-terminal purified protein of QRICH2 shows promise as an additive for protecting spermatozoa during preservation and cryopreservation.

Systematic analyses of the factors influencing sperm quality in patients with SARS-CoV-2 infection.

To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.

Application research of novel peptide mitochondrial-targeted antioxidant SS-31 in mitigating mitochondrial dysfunction.

Due to the pivotal role of mitochondria in the generation of adenosine triphosphate (ATP) and the regulation of cellular homeostasis, mitochondrial dysfunction may exert a profound impact on various physiological systems, potentially precipitating a spectrum of distinct diseases. Consequently, research pertaining to mitochondrial therapeutics has assumed increasing significance, warranting heightened scrutiny. In recent years, the field of mitochondrial therapy has witnessed noteworthy advancements, with active exploration into diverse pharmacological agents aimed at ameliorating mitochondrial function. Elamipretide (SS-31), a novel synthetic mitochondrial-targeted antioxidant, has emerged as a promising candidate with extensive therapeutic potential. Its notable attributes encompass the mitigation of oxidative stress, the suppression of inflammatory processes, the maintenance of mitochondrial dynamics, and the prevention of cellular apoptosis. As such, SS-31 may emerge as a viable choice for the treatment of mitochondrial dysfunction-related ailments in the foreseeable future. This article extensively expounds upon the superiority of SS-31 over natural antioxidants and traditional mitochondrial-targeted antioxidants, delves into its mechanisms of modulating mitochondrial function, and comprehensively summarizes its applications in alleviating mitochondrial dysfunction-associated disorders. Furthermore, we offer a comprehensive outlook on the expansive prospects of SS-31's future development and application.

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein.

Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtubules within eukaryotic cells. However, in mammals, few mutants are available for studying the effects of defects in dynein-controlled processes in the context of the whole organism. Here, we deleted mouse Dlic1 gene encoding DLIC1, a subunit of the dynein complex. Dlic1(-/-) mice are viable, but display severe photoreceptor degeneration. Ablation of Dlic1 results in ectopic accumulation of outer segment (OS) proteins, and impairs OS growth and ciliogenesis of photoreceptors by interfering with Rab11-vesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body. Our studies show that Dlic1 deficiency partially blocks vesicle export from endoplasmic reticulum (ER), but seems not to affect vesicle transport from the ER to Golgi. Further mechanistic study reveals that lack of Dlic1 destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors, probably due to the impaired transport function of dynein. Our results demonstrate that Dlic1 plays important roles in ciliogenesis and protein transport to the OS, and is required for photoreceptor development and survival. The Dlic1(-/-) mice also provide a new mouse model to study human retinal degeneration.