Testosterone regulation on quiescin sulfhydryl oxidase 2 synthesis in the epididymis

Abstract

The epididymis is an androgen-responsive organ, whose structure and functions are modulated by the coordination between androgen and epididymal cues. Highly-regulated molecular interaction within the epididymis is required to support viable sperm development necessary for subsequent fertilization. In the present study, we extended our earlier findings on a promising epididymal protein, quiescin sulfhydryl oxidase 2 (QSOX2), and demonstrated a positive correlation between testosterone and QSOX2 protein synthesis through use of loss- and restore-of-function animal models. Moreover, based on transcriptomic analyses and 2-dimensional culture system, we determined that an additional polarized effect of glutamate is indispensable for the regulatory action of testosterone on QSOX2 synthesis. In conclusion, we propose non-canonical testosterone signaling supports epididymal QSOX2 protein synthesis, providing a novel perspective on the regulation of sperm maturation within the epididymis.

Polarized epithelium-sperm co-culture system reveals stimulatory factors for the secretion of mouse epididymal quiescin sulfhydryl oxidase 1

“…In most cases, epididymal protein expression and secretion are regulated by luminal factors [ 19 ], and to demonstrate whether sperm cells or other stimuli ( e.g. , steroid hormones) affect QSOX1 protein expression and secretion, we applied the castration model, as described earlier [ 19 ]. As shown in Fig.…”

“…Luminal detection of QSOX1c suggested that this protein is secreted into the lumen by the epididymal epithelium and likely plays a role at different maturation stages of spermatozoa [ 18 ]. In an earlier study, we showed that the expression and secretion of mouse epididymal QSOX2 is regulated by a fine coordinated mechanism between testosterone and glutamate [ 19 ]. Although we also demonstrated that mouse QSOX1c could aggregate defective human and mouse sperm in vitro and in vivo [ 20 ], the regulatory mechanism directing QSOX1c secretion remains unknown.…”

QSOX2 Upregulated in triple-negative breast cancer exacerbates patient prognosis by stabilizing integrin β1

“…Maharaj et al linked it to human growth regulation, associated with postnatal growth delay and mild immune issues [ 31 ]. Wang et al explored the relationship between testosterone and QSOX2, demonstrating the constructive role of testosterone in QSOX2 biogenesis [ 32 ]. In cancer, only two studies have reported the molecular effects of QSOX2.…”

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx

“…The cDNA synthesis was performed by DNA Polymerase I and RNase H, and the cDNA library was established as previously described. 34 NextSeq500 (Illumina Inc., CIC bioGUNE, Bilbao, Spain) was used to obtain 10 million reads for each sample. High-quality reads were aligned to the Mus musculus genome GCRm38 assembly from the ICR strain using the Ensembl platform.…”