Gender Differences in Quality of Life of Adolescent Patients With Chronic Rhinosinusitis.

OBJECTIVES: To identify the differences in the impact of chronic rhinosinusitis (CRS) between female and male adolescent patients at presentation. STUDY DESIGN: Cross sectional study. METHODS: Adolescent patients, age 12 to 18 years old, presenting to our Otolaryngology clinic between August 2020 and April 2023 for CRS were asked to fill both the SNOT-22 and the SN5 forms. Female and male cohorts were compared regarding their demographics, comorbidities, subjective and objective disease measurements, and choice of treatment. RESULTS: Sixty-six patients were included, 30 female and 36 male patients. There were no differences in age, allergic rhinitis, asthma, obstructive sleep apnea, presence of nasal septal deviation, and objective disease severity (P > .05 for all). At presentation, mean overall SNOT-22, ear/facial, sleep, and psychological domains were all higher in female patients (43vs 30.9, P = .02; 9.1vs 6, P = .03; 11.8vs 8.3, P = .07; 14.1vs 8.8, P = .02 respectively). SN5 scores and overall QoL visual analog scale were similar in females and males. CONCLUSION: Female patients with CRS show higher subjective disease burden. Incorporating data on gender-specific differences may be important to personalize treatment decision making.

SP22 sperm protein as a potential biomarker of fertility in humans: A preliminary study.

Infertility affects approximately 15% of couples of reproductive age, and 50% of the cases are directly related to men. The evaluation of male fertility is based on analyses of routine seminal parameters and the use of more advanced techniques can help identify fertility biomarkers. SP22 sperm protein is considered a biomarker in murine species since its concentration is highly correlated with sperm fertility. As the role of this protein as a biomarker is already well-established in other species, we hypothesized that this same correlation could apply to human. Thus, the present study aimed to investigate possible correlations between SP22 concentration and sperm parameters in fertile and infertile men. For this, a study was carried out on 21 volunteers' seminal samples who were grouped according to fertility as fertile (n = 10) or infertile (n = 11). Conventional and functional sperm analyses, membrane protein extraction, quantification and immunolocalization of SP22 were performed. The infertile volunteers showed an increase in the percentage of sperm with abnormalities in head morphology and a decrease in the percentage of sperm with intact plasma membrane and damaged acrosomal membrane. Serum concentration of the hormone SHBG was also decreased in infertile volunteers. The damage to the plasma membrane was positively correlated with the superoxide anion production. Although none of the functional parameters were correlated with SP22 concentration, type D sperm motility was negatively correlated and type A+B sperm motility was positively correlated. This preliminary study opens new paths in the characterization of SP22 as a non-invasive biomarker for predicting fertility/infertility.

Mobile ARGONAUTE 1d binds 22-nt miRNAs to generate phasiRNAs important for low-temperature male fertility in rice.

Phased small interfering RNAs (phasiRNAs) are abundantly expressed in anthers and linked to environment-related male fertility in grasses, yet how they function under different environmental conditions remains unclear. Here, we identified a rice (Oryza sativa) low temperature-induced Argonaute (AGO) protein, OsAGO1d, that is responsible for generating phasiRNAs and preserving male fertility at low temperature. Loss of OsAGO1d function causes low-temperature male sterility associated with delayed programmed cell death of tapetal cells during anther development. OsAGO1d binds miR2118 and miR2275 family members and triggers phasiRNA biogenesis; it also binds 21-nt phasiRNAs with a 5' terminal U. In total, phasiRNAs from 972 loci are OsAGO1d-dependent. OsAGO1d protein moves from anther wall cells into meiocytes, where it loads miR2275 to produce 24-nt phasiRNAs. Together, our results show that OsAGO1d acts as a mobile signal to fine-tune phasiRNA production and this function is important for male fertility at low temperature.

Aortic Arch Laterality in Chromosome 22q11.2 Deletion Syndrome: Male-Female Difference.

We reviewed patients with chromosome 22q11.2 deletion syndrome. We analyzed cardiovascular findings in patients with confirmed chromosome 22q11.2 deletion syndrome live-born in Nevada between March 2007 and September 2020. We identified 60 patients. Of the 60 patients, 32 (53%) were female. Of the 60, 48 (80%) had a conotruncal abnormality (including isolated vascular rings): 23 of 32 (72%) for females versus 25 of 28 (89%) for males, P = .41. However, 11 (34%) of 32 females had a right aortic arch; whereas, 21 (75%) of 28 males had a right aortic arch, P = .007. In conclusion, in our patient cohort, we found conotruncal malformations were common. However, we noted males were statistically more likely to have a right aortic arch than females. To the best of our knowledge, this male-female aortic arch laterality difference in patients with chromosome 22q11.2 deletion syndrome has not been previously noted.

lncRNA 1700101O22Rik and NONMMUG030480.1 Are Not Essential for Spermatogenesis in Mice.

Many testis-specific lncRNAs are highly expressed in late spermatogenesis, especially in spermiogenesis. However, their functions and the underlying mechanisms in male fertility are largely unknown. Here, we screened two highly expressed lncRNAs, 1700101O22Rik (O22Rik) and NONMMUG030480.1 (NM480) in testes, to investigate the roles in spermatogenesis using lncRNA knockout (KO) mouse generated by CRISPER/Cas9 technology. Both testis-specific lncRNAs were mainly expressed from secondary spermatocytes to round spermatids, suggesting that they might be involved in spermiogenesis. Phenotypic analysis showed that the deletion of O22Rik or NM480 did not affect the development of testis and epididymis or spermatogenesis. These results were confirmed in both young and middle-aged male mice. In addition, there was no significant difference in sperm morphology and other parameters including concentration and motility between wild type (WT) and KO mice. Fertility tests showed that litter size was significantly lower in O22Rik KO mice compared with WT controls. Although O22Rik did not exert dramatic roles in spermatogenesis, on molecular levels, its surrounding gene expression was disturbed significantly. Gm32773 was decreased; however, Gm32828 was increased in KO mice. In conclusion, lncRNA O22Rik and NM480 are not individually essential for spermatogenesis in mice.

Examining the Role of Traditional Masculinity and Depression in Men's Risk for Contracting COVID-19.

In the light of the COVID-19 pandemic and claims that traditional masculinity may put some men at increased risk for infection, research reporting men's health behaviors is critically important. Traditional masculine norms such as self-reliance and toughness are associated with a lower likelihood to vaccinate or follow safety restrictions. Furthermore, infection risk and traditional masculinity should be investigated in a differentiated manner including gender role orientation, underlying traditional masculine ideologies and male gender role conflict. In this pre-registered online survey conducted during March/April 2021 in German-speaking countries in Europe, 490 men completed questionnaires regarding contracting COVID-19 as confirmed by a validated test, fear of COVID-19 (FCV-19S), and experience of psychological burden due to COVID-19. In addition, depression symptomatology was assessed by using prototypical internalizing and male-typical externalizing depression symptoms. Furthermore, self-identified masculine gender orientation, endorsement of traditional masculinity ideologies, and gender role conflict were measured. A total of 6.9% of men (n = 34) reported having contracted COVID-19 since the beginning of the pandemic. Group comparisons revealed that men who had contracted COVID-19 exhibited higher overall traditional masculine ideology and gender role conflict. Logistic regression controlling for confounders (age, income, education, and sexual orientation) indicated that only depression symptoms are independently associated with the risk of having contracted COVID-19. While prototypical depression symptoms were negatively associated with the risk of having contracted COVID-19, male-typical externalizing depression symptoms were positively associated with the risk of contracting COVID-19. For traditional masculinity, no robust association for an increased risk of contracting COVID-19 could be established, while higher male-typical externalizing depression symptoms were associated with an increased risk of contracting COVID-19.

Men's Psychotherapy Use, Male Role Norms, and Male-Typical Depression Symptoms: Examining 716 Men and Women Experiencing Psychological Distress.

Men as compared to women are half as often affected by depressive and anxiety disorders and seek significantly less help for mental health issues than women. Adherence to traditional male role norms (AtTMRN) may hinder men from describing prototypical depression symptoms and from seeking psychotherapy. The current study compared whether AtTMRN, gender role identity, or the experience of prototypical or male-typical externalizing mental health symptoms were associated with psychotherapy use in men and women. In an anonymous online survey, 716 participants (37% men) reporting to currently experience psychological distress were examined. Information was obtained on psychotherapy use, depression and anxiety symptoms, gender role identity, and traditional male role norms. Although experiencing similar levels of depression, men compared to women showed a reduction in psychotherapy use by 29%. Masculine role identity was directly associated with reduced psychotherapy use in men (ß = -0.41, p = 0.029), whereas AtTMRN was not (men: ß = -0.04, p = 0.818; women: ß = -0.25, p = 0.064). Higher externalizing depression symptomatology (ß = -0.68, p = 0.005), but not prototypical depression symptomatology (ß = -0.02, p = 0.499), was associated with reduced psychotherapy use in men but not women (p > 0.05). Interactions revealed that men, but not women, with high AtTMRN use psychotherapy only when exhibiting elevated symptom levels. The results corroborate previous reports showing reduced psychotherapy use in men as compared to women and identify elevated masculine role identity and male-typical externalizing depression symptomatology as direct factors associated with reduced psychotherapy use in psychologically distressed men. AtTMRN interacts with mental health symptoms to predict psychotherapy use, indicating that men with high AtTMRN only use psychotherapy when exhibiting high symptomatology.

SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility.

Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid ß-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. We demonstrate that Slc22a14-mediated FAO is essential for spermatozoa energy generation and motility. Furthermore, sperm from wild-type mice treated with a riboflavin-deficient diet mimics those in Slc22a14 knockout mice, confirming that an altered riboflavin level causes spermatozoa morphological and bioenergetic defects. Beyond substantially advancing our understanding of spermatozoa energy metabolism, our study provides an attractive target for the development of male contraceptives.

A cell-based high-content screen identifies isocotoin as a small molecule inhibitor of the meiosis-specific MEIOB-SPATA22 complex†.

MEIOB and SPATA22 are meiosis-specific proteins, interact with each other, and are essential for meiotic recombination and fertility. Aspartic acid 383 (D383) in MEIOB is critical for its interaction with SPATA22 in biochemical studies. Here we report that genetic studies validate the requirement of D383 for the function of MEIOB in mice. The MeiobD383A/D383A mice display meiotic arrest due to depletion of both MEIOB and SPATA22 proteins in the testes. We developed a cell-based bimolecular fluorescence complementation (BiFC) assay, in which MEIOB and SPATA22 are fused to split YFP moieties and their co-expression in cultured cells leads to the MEIOB-SPATA22 dimerization and reconstitution of the fluorophore. As expected, the interaction-disrupting D383A substitution results in the absence of YFP fluorescence in the BiFC assay. A high-throughput screen of small molecule libraries identified candidate hit compounds at a rate of 0.7%. Isocotoin, a hit compound from the natural product library, inhibits the MEIOB-SPATA22 interaction and promotes their degradation in HEK293 cells in a dose-dependent manner. Therefore, the BiFC assay can be employed to screen for small molecule inhibitors that disrupt protein-protein interactions or promote degradation of meiosis-specific proteins.

Organic cation/carnitine transporter OCTN2 (SLC22A5) -207C>G (rs2631367) polymorphism is not associated with male infertility.

Carnitine is an important factor in the initiation of progressive sperm motility and end stage of sperm maturation. The compound is transported by an organic cation/carnitine transporter (OCTN2), which is expressed in the male reproductive system. OCTN2 is encoded by SLC22A5 gene with proven -207C>G functional polymorphism. The aim of the case-control study was to investigate a potential association between the -207C>G SLC22A5 polymorphism and male infertility. The -207C>G SLC22A5 polymorphism was determined by means of TaqMan assay in 206 infertile Caucasian males and 256 ethnically matched controls. Besides genotyping study, sperm mitochondrial function was assessed using NADH-dependent NBT assay. The distribution of SLC22A5 genotypes in infertile men was as follows: CC - 29.6%, CG - 53.9%, GG - 16.5% and in fertile men: CC - 32.0%, CG - 50.0%, GG - 18.0%, and was comparable in both evaluated groups. Likewise, the studied polymorphism did not affect sperm mitochondrial function. The results of the current study demonstrated that -207C>G polymorphism of the SLC22A5 gene is not associated with male infertility.

RpL22e, but not RpL22e-like-PA, is SUMOylated and localizes to the nucleoplasm of Drosophila meiotic spermatocytes.

Duplicated ribosomal protein (Rp) gene families often encode highly similar or identical proteins with redundant or unique roles. Eukaryotic-specific paralogues RpL22e and RpL22e-like-PA are structurally divergent within the N terminus and differentially expressed, suggesting tissue-specific functions. We previously identified RpL22e-like-PA as a testis Rp. Strikingly, RpL22e is detected in immunoblots at its expected molecular mass (m) of 33 kD and at increasing m of ~43-55 kD, suggesting RpL22e post-translational modification (PTM). Numerous PTMs, including N-terminal SUMOylation, are predicted computationally. Based on S2 cell co-immunoprecipitations, bacterial-based SUMOylation assays and in vivo germline-specific RNAi depletion of SUMO, we conclude that RpL22e is a SUMO substrate. Testis-specific PTMs are evident, including a phosphorylated version of SUMOylated RpL22e identified by in vitro phosphatase experiments. In ribosomal profiles from S2 cells, only unconjugated RpL22e co-sediments with active ribosomes, supporting an extra-translational role for SUMOylated RpL22e. Ectopic expression of an RpL22e N-terminal deletion (lacking SUMO motifs) shows that truncated RpL22e co-sediments with polysomes, implying that RpL22e SUMOylation is dispensable for ribosome biogenesis and function. In mitotic germ cells, both paralogues localize within the cytoplasm and nucleolus. However, within meiotic cells, phase contrast microscopy and co-immunohistochemical analysis with nucleolar markers nucleostemin1 and fibrillarin reveals diffuse nucleoplasmic, but not nucleolar RpL22e localization that transitions to a punctate pattern as meiotic cells mature, suggesting an RpL22e role outside of translation. Germline-specific knockdown of SUMO shows that RpL22e nucleoplasmic distribution is sensitive to SUMO levels, as immunostaining becomes more dispersed. Overall, these data suggest distinct male germline roles for RpL22e and RpL22e-like-PA.