Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice.

BACKGROUND: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. RESULTS: We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. CONCLUSION: Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.

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

Spermatozoa acquire fertilization ability through post-translational modifications. These membrane surface alterations occur in various segments of the epididymis. Quiescin sulfhydryl oxidases, which catalyze thiol-oxidation reactions, are involved in disulfide bond formation, which is essential for sperm maturation, upon transition and migration in the epididymis. Using castration and azoospermia transgenic mouse models, in the present study, we showed that quiescin sulfhydryl oxidase 1 (QSOX1) protein expression and secretion are positively correlated with the presence of testosterone and sperm cells. A two-dimensional in vitro epithelium-sperm co-culture system provided further evidence in support of the notion that both testosterone and its dominant metabolite, 5α-dihydrotestosterone, promote epididymal QSOX1 secretion. We also demonstrated that immature caput spermatozoa, but not mature cauda sperm cells, exhibited great potential to stimulate QSOX1 secretion in vitro, suggesting that sperm maturation is a key regulatory factor for mouse epididymal QSOX1 secretion. Proteomic analysis identified 582 secretory proteins from the co-culture supernatant, of which 258 were sperm-specific and 154 were of epididymal epithelium-origin. Gene Ontology analysis indicated that these secreted proteins exhibit functions known to facilitate sperm membrane organization, cellular activity, and sperm-egg recognition. Taken together, our data demonstrated that testosterone and sperm maturation status are key regulators of mouse epididymal QSOX1 protein expression and secretion.

Absence of an Association between Macular Degeneration and Young-Onset Dementia.

A few population-based studies have reported an association between prior age-related macular degeneration and senile dementia. No study has explored a possible link between prior macular degeneration and young-onset dementia (YOD). This case-control study aimed to evaluate the association of YOD with prior macular degeneration diagnosed in the 5-year period before their index date. Data for this retrospective observational study were retrieved from Taiwan's National Health Insurance (NHI) dataset. A total of 36,577 patients with newly diagnosed YOD from January 2010 to December 2017 were identified as the study cohort, assigning their diagnosis date as their index date. Comparison patients were identified by propensity score-matching (three per case, n = 109,731 controls) from the remaining NHI beneficiaries of the period, their index date being the date of their first ambulatory care claim in the year of diagnosis of their matched YOD case. Chi-square test revealed no significant difference in the prevalence of prior macular degeneration between cases and controls (1.1% vs. 1.0%, p = 0.111). Conditional logistic regression analysis also showed an unadjusted odds ratio (OR) for prior macular degeneration of 1.098 among cases relative to controls (95% CI: 0.9797-1.232). Adjusted analysis confirmed that YOD was not associated with prior macular degeneration, adjusted odds ratio 1.098 (95% CI = 0.979-1.232). We conclude that patients with macular degeneration are not at increased risk for YOD.