Y chromosome polymorphisms contribute to an increased risk of non-obstructive azoospermia: a retrospective study of 32,055 Chinese men.

PURPOSE: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.

Development and validation predictive models of sperm retrieval for azoospermic men undergoing testicular sperm aspiration: a multicentre, retrospective, cohort study.

PURPOSE: Testicular sperm aspiration (TESA) is widely used to retrieve sperm from testis. Diagnostic testicular biopsy should not be routinely performed for azoospermia. Therefore, a good predictive model is needed before TESA. METHODS: A total of 1972 azoospermia patients constituted the modelling set, and 260 azoospermia patients from two other centres constituted the validation set. An integrated predictive model was built using logistic regression. Receiver operating characteristic (ROC), calibration and decision curve analyses were performed to evaluate the performance of follicle-stimulating hormone (FSH), semen volume, testicular volume and the integrated model. RESULTS: The FSH level was the best univariate predictor for successful sperm retrieval (SSR) and was better than semen volume and testicular volume alone (p<0.001, threshold 6.17 IU/L, modelling set area under receiver operating characteristic curve (AUC) 0.80, accuracy 0.79; validation set AUC 0.87, accuracy 0.78). The integrated predictive model had excellent accuracy for predicting SSR (modelling set: AUC 0.93, accuracy 0.89; validation set: AUC 0.96, accuracy: 0.89). Calibration curve analysis indicated that the integrated model calibration was good and better than that of FSH, semen volume and testicular volume alone. Decision curve analysis indicated with a threshold probability between 0.05 and 0.98, the integrated model added more benefit than treating either all or no patients. CONCLUSIONS: The integrated model has excellent discrimination and good calibration. It can help azoospermic men make better decisions before TESA. It should be noted that TESA is not the first-line treatment for non-obstructive azoospermia because of a low sperm retrieval rate.

Sperm DNA fragmentation and male fertility: a retrospective study of 5114 men attending a reproductive center.

PURPOSE: The sperm DNA fragmentation index (DFI) was quantitatively measured and its relationship with age, semen quality, and infertility conditions was investigated. METHODS: Semen routine test and sperm DFI were performed in 2760 infertile male and 2354 male whose spouse experienced at least one unexplained miscarriage to analyze the correlation between sperm DNA damage, semen routine parameters, and age. RESULTS: Sperm DFI was significantly lower from patients whose wife experienced unexplained miscarriage compared to infertility males (p = 0.000). An inverse correlation between sperm DFI and sperm progressive motility was observed (rs = - 0.465, p = 0.000) and sperm DFI was positively correlated with age (rs = 0.255, p = 0.000). However, the correlation between sperm DFI and sperm concentration, semen volume, total sperm count, and motile sperm count were not proved. CONCLUSIONS: Sperm DFI is an important indicator for evaluating the quality of semen. Sperm DNA integrity testing is preferentially recommended to those who have decreased sperm progressive motility, especially older men. An integrative analysis of sperm DFI, sperm progressive motility, age, and infertility conditions can provide a more comprehensive assessment of male fertility.

Improved oral bioavailability and anti-chronic renal failure activity of chrysophanol via mixed polymeric micelles.

AIMS: This study was designed to prepare chrysophanol-loaded micelles (CLM) to improve the oral bioavailability, targetability and anti-chronic renal failure (CRF) activity of chrysophanol (CH). METHODS: The preparation of CLM was achieved via thin-film dispersion technique. The in vitro release of CLM compared with free CH was measured in phosphate buffer solution (PBS) containing 0.5%w/v sodium dodecyl sulphate (pH 6.8) while the pharmacokinetic and anti-CRF activity study was also conducted in rats. Moreover, the tissue distribution of CLM was investigated in the mice. RESULTS: The CLM had particle size (PS) of 29.64 ± 0.71 nm, and encapsulation efficiency (EE) of 90.48 ± 1.22%w/w. The cumulative release rate of CH from the micellar system was significantly higher than that of the free CH (86%m/m vs. 15%m/m, p < 0.01). In vivo pharmacokinetic studies showed that the bioavailability of CLM after oral administration was substantially improved (about 3.4 times) compared with free drugs (p < 0.01). Also, it was observed that CLM accumulated well in the liver and brain. Moreover, in vitro renal podocytes study showed that CLM had better protection against renal podocyte damage than the free CH. In addition, CLM significantly (p < 0.01) reduced levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), and serum creatinine (SCr), which obviously improved kidney damage in rats with CRF. CONCLUSIONS: Collectively, these findings suggest that mixed micelles may be used as a promising drug delivery system for oral bioavailability improvement and concomitantly enhance the anti-CRF activity of CH, as well as provide a basis for the clinical application of CH.

Altered expression of DNA damage repair genes in the brain tissue of mice conceived by in vitro fertilization.

Our previous study revealed a higher incidence of gene dynamic mutation in newborns conceived by IVF, highlighting that IVF may be disruptive to the DNA stability of IVF offspring. However, the underlying mechanisms remain unclear. The DNA damage repair system plays an essential role in gene dynamic mutation and neurodegenerative disease. To evaluate the long-term impact of IVF on DNA damage repair genes, we established an IVF mouse model and analyzed gene and protein expression levels of MSH2, MSH3, MSH6, MLH1, PMS2, OGG1, APEX1, XPA and RPA1 and also the amount of H2AX phosphorylation of serine 139 which is highly suggestive of DNA double-strand break (γH2AX expression level) in the brain tissue of IVF conceived mice and their DNA methylation status using quantitative real-time PCR, western blotting and pyrosequencing. Furthermore, we assessed the capacity of two specific non-physiological factors in IVF procedures during preimplantation development. The results demonstrated that the expression and methylation levels of some DNA damage repair genes in the brain tissue of IVF mice were significantly changed at 3 weeks, 10 weeks and 1.5 years of age, when compared with the in vivo control group. In support of mouse model findings, oxygen concentration of in vitro culture environment was shown to have the capacity to modulate gene expression and DNA methylation levels of some DNA damage repair genes. In summary, our study indicated that IVF could bring about long-term alterations of gene and protein expression and DNA methylation levels of some DNA damage repair genes in the brain tissue and these alterations might be resulted from the different oxygen concentration of culture environment, providing valuable perspectives to improve the safety and efficiency of IVF at early embryonic stage and also throughout different life stages.

Decreased expression of MRE11 and RAD50 in testes from humans with spermatogenic failure.

PURPOSE: To assess testicular mRNA and protein expression levels of MRE11 and RAD50 in human azoospermia patients. METHODS: Patients diagnosed with maturation arrest at the spermatocyte stage (MA) and Sertoli cell-only syndrome (SCOS) were recruited through diagnostic testicular biopsy. Patients with normal spermatogenesis were studied as controls. In addition, knockdown of MRE11 and RAD50 was performed in GC-2spd(ts) cells to investigate their roles in cellular proliferation and apoptosis. RESULTS: mRNA and protein expression levels of MRE11 and RAD50 were measured using quantitative polymerase chain reaction, western blotting, and immunohistochemistry, respectively. Knockdown of both MRE11 and RAD50 utilized transfection with small interfering RNAs. CONCLUSION: Our findings demonstrated altered expression levels of MRE11 and RAD50 in human testes with MA and SCOS, and showed that these alterations might be associated with impaired spermatogenesis. These results offer valuable new perspectives into the molecular mechanisms of male infertility.

Seminal plasma HSPA2 mRNA content is associated with semen quality.

PURPOSE: Cell-free mRNAs (cfmRNAs) were quantitatively measured in human seminal plasma and its relationship with semen quality was investigated. METHODS: Herein, a prospectively, controlled investigation was performed to study seminal plasma HSPA2 and uPA cfmRNA alterations between 21 asthenozoospermic patients and 16 normozoospermic individuals. Standard semen analysis was performed and seminal plasma cfmRNAs content was measured by real-time quantitative PCR. In addition, the regression analysis between seminal plasma cfmRNAs expression and semen parameters was performed. RESULTS: Seminal plasma HSPA2, but not uPA cfmRNA indicated significant difference between normozoospermia and asthenozoospermia men (P = 0.02444 and 0.07811, respectively). Negative correlation between HSPA2 cfmRNA and sperm motility (R (2) = 0.213, P = 0.004) as well as sperm concentration (R (2) = 0.133, P = 0.026) were revealed. However, no correlation was found between seminal plasma uPA cfmRNA content and semen parameters. CONCLUSIONS: Our data suggest that seminal plasma HSPA2 cfmRNA is different between asthenozoospermic and normozoospermic individuals and it might be an indicator for semen quality.

[Microsurgical treatment of obstructive azoospermia: a report of 76 cases].

OBJECTIVE: To investigate the clinical effect of microsurgical vasoepididymostomy and/or vasovasostomy in the treatment of obstructive azoospermia. METHODS: This study included 76 patients with obstructive azoospermia, 53 treated by bilateral vasoepididymostomy (8 involving the epididymal head, 18 involving the epididymal body, 5 involving the epididymal tail, and 22 involving the epididymal head, body and tail), 14 by unilateral vasoepididymostomy, and the other 9 by unilateral vasoepididymostomy + unilateral vasovasostomy (including cross anastomosis). We followed up the patients for 2 to 16 months for the patency rate, routine semen parameters, and pregnancy outcomes. RESULTS: The success rate of bilateral vasoepididymostomy, unilateral vasoepididymostomy, and unilateral vasoepididymostomy + unilateral vasovasostomy (including cross anastomosis) were 62.26% (33/53), 35.71% (5/14), and 77.78% (7/9), respectively. The average sperm concentrations in the three groups of patients were (27.9 +/- 5.74), (11.8 +/- 8.33), and (19.9 +/- 7.53) x 10(6)/ml, the average total sperm counts were (65.6 +/- 13.71), (28.0 +/- 15.86), and (69.2 +/- 28.59) x 10(6), and the mean rates of progressively motile sperm were (22.3 +/- 3.18), (11.0 +/- 9.77), and (15.8 +/- 5.05)%, respectively. The success rates of bilateral vasoepididymostomy that involved the epididymal head, body, tail, and all the three parts were 62.5, 72.22, 60, and 54.55%, respectively. Natural pregnancy was achieved in 8 (10.53%) of the total number of cases. CONCLUSION: Microsurgery is effective for the treatment obstructive azoospermia. Unilateral vasoepididymostomy + unilateral vasovasostomy is superior to the other procedures, followed by bilateral vasoepididymostomy. Bilateral vasoepididymostomy involving the epididymal body may achieve a slightly better effect than that involving the other epididymal parts.

Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization.

In conventional in vitro fertilization (IVF), complete failure of fertilization occurs in 5% to 15% of treatments. Although the causes may be unclear, sperm defects appear to be the major contributor. However, a convincing test is not yet available that can predict the risk of fertilization failure. In this study, we found that germinal angiotensin-converting enzyme (gACE) (also called testicular ACE) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower fertilization rates (LFRs) by IVF based on Western blot and indirect immunofluorescence analyses. Additionally, almost all of the patients without gACE on sperm (23 of 25) manifested a TT genotype of the rs4316 single-nucleotide polymorphism of ACE. Overall, our results indicate that the absence of gACE expression is responsible for TFF and LFRs by IVF. The rs4316 polymorphism of ACE might be associated with infertility in those patients. We conclude that sperm lacking gACE may be recognized before commencing IVF and that the patients may be directed instead to consider intracytoplasmic sperm injection.

Depression of HspA2 in human testis is associated with spermatogenic impairment and fertilization rate in ICSI treatment for azoospermic individuals.

PURPOSE: Heat shock protein A2 (HspA2) expression was quantitatively measured in human testis and its relationship with the spermatogenetic status and laboratory outcomes of intracytoplasmic sperm injection (ICSI) was investigated. METHODS: Testicular tissues of azoospermia men were divided into four groups according to histopahtology: normal spermatogenesiss, hypospermatogenesis, maturation arrest and Sertoli cell-only syndrome (SCOS). HspA2 immunostaining was measured by Image Pro-Plus (IPP) and laboratory outcomes were calculated. The regression analysis between HspA2 expression and Johnsen score of as well as fertilization, cleavage and high quality embryo rate was performed. RESULTS: HspA2 was strongly present in the cytoplasm of spermatocytes and spermatides in normal testis. However, hypospermatogenesis and maturation arrest testicular tissues demonstrated light staining and no staining for SCOS. Quantitative image analysis showed that there were significant differences among groups (P = 0.000 & P = 0.001). HspA2 exspression was founded significantly correlated spermatogenetic status (R(2) = 0.726, P = 0.000) as well as fertilization rate in ICSI (R(2) = 0.569, P = 0.000). CONCLUSIONS: The fertilization rate with ICSI is associated with HspA2 expression in the testis from which sperm retrieved and the alteration of HspA2 expression has been involved in spermatogenic impairment.

Correlations of religious beliefs with anxiety and depression of Chinese adolescents.

Objective: This study was designed to investigate the prevalence of religious belief and its relationship with psychiatric symptoms among Chinese adolescents. Methods: This study recruited 11,603 adolescents in Grades 7-9 from March 21 to 31, 2020 in five cities in China. The religious beliefs of adolescents were collected by asking whether they held religious beliefs and what type of religious beliefs they held. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) were used to assess depressive and anxiety symptoms in all adolescents. Demographics, religious beliefs, and mental health status were collected through the professional version of Wenjuanxing. Results: Of 11,069 valid questionnaires collected, 847 (7.7%) reported holding religious beliefs. Adolescents with religious beliefs showed significantly more severe symptoms of depression and anxiety compared to those without religious beliefs (both p<0.05). Logistic regression analysis revealed that religious belief was a risk factor for symptoms of depression (OR = 1.37, 95%CI: 1.16-1.61, p < 0.001) and anxiety (OR = 1.49, 95%CI: 1.23-1.79, p < 0.001) after controlling age, gender, and parental marital status. Conclusions: Our findings suggest that religiousness in adolescents was associated with a higher likelihood of depression/more intense depressive symptoms. In addition, religious Chinese adolescents should be provided with more resources to help them cope with mental health concerns.

Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans.

Oligo-astheno-teratozoospermia (OAT), which is a common cause of male infertility, can be caused by genetic factors. This study reports on a case of a male patient suffering from infertility concomitant with OAT. Whole-exome sequencing (WES) confirmed the presence of a homozygous variant (NM_003462: c.464-1G > A) in the DNALI1 gene via Sanger sequencing. Immunofluorescence staining demonstrated that the DNALI1 signal was nearly undetectable in the patient's sperm. Bioinformatics analysis revealed that this mutation could reverse the splicing of the exon 4 acceptor splice site. A minigene experiment was performed to verify the mutation and the results confirmed that the mutation disrupted the splicing. Our findings show that this rare mutation in DNALI1 contributes to male infertility and OAT in humans, thereby expanding our understanding of the causes and pathogenesis of male infertility. This knowledge facilitates genetic counseling, clinical diagnosis, and therapeutic development of male infertility.

MRE11 is essential for the long-term viability of undifferentiated spermatogonia.

In the meiotic prophase, programmed SPO11-linked DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR). The MRE11-RAD50-NBS1 (MRN) complex is essential for initiating DNA end resection, the first step of HR. However, residual DNA end resection still occurs in Nbs1 knockout (KO) spermatocytes for unknown reasons. Here, we show that DNA end resection is completely abolished in Mre11 KO spermatocytes. In addition, Mre11 KO, but not Nbs1 KO, undifferentiated spermatogonia are rapidly exhausted due to DSB accumulation, proliferation defects, and elevated apoptosis. Cellular studies reveal that a small amount of MRE11 retained in the nucleus of Nbs1 KO cells likely underlies the differences between Mre11 and Nbs1 KO cells. Taken together, our study not only demonstrates an irreplaceable role of the MRE11 in DNA end resection at SPO11-linked DSBs but also unveils a unique function of MRE11 in maintaining the long-term viability of undifferentiated spermatogonia.

Re-assessment of the close relationship between serum FSH levels and semen quality: a retrospective cohort study of 11,929 Chinese men.

PURPOSE: To establish a medically valuable normal reference interval of follicle-stimulating hormone (FSH) levels in males with normal semen and to assess the predictive value of FSH in males exhibiting semen abnormalities. METHODS: The study involved male patients who underwent their initial serum sex hormone test and semen test between October 2013 and June 2023. The reference interval was identified as the 95% confidence interval (CI) of FSH values in the patients with normal semen parameters. Then, in the total study population, receiver operating characteristic (ROC) curves were performed to evaluate the discriminatory ability of FSH for oligozoospermia and non-obstructive azoospermia (NOA). Besides, multivariable logistic regression was performed to investigate the association of FSH with oligozoospermia and NOA adjusted by age. RESULTS: A total of 11,929 patients were finally enrolled in the study. The normal reference interval of FSH ranged from 1.70 IU/L to 7.60 IU/L (median: 3.98 IU/L) based on 4595 patients with normal semen routine parameters. In the total patients, ROC curves showed FSH to have a "fair" discriminatory ability for oligozoospermia (area under receiver operating characteristic curve (AUC) 0.747, threshold 7.32 IU/L, accuracy 0.734, positive predictive value (PPV) 0.754, negative predictive value (NPV) 0.726), while ROC curves showed FSH to have a "excellent" discriminatory ability for NOA (AUC: 0.921, threshold 10.18 IU/L, accuracy 0.903, PPV 0.593, NPV 0.972). Besides, multivariable logistic regression showed that FSH ≥ 7.32 IU/L was associated with a 8.51-fold increase in the risk of oligozoospermia adjusted by age, while FSH ≥ 10.18 IU/L was associated with a 38.93-fold increase in the risk of NOA. CONCLUSIONS: Our findings indicated that the reference interval for FSH in males with normal semen was 1.70-7.60 IU/L and found that FSH was capable of effectively discerning oligospermia and NOA.

An automatic classification method of testicular histopathology based on SC-YOLO framework.

The pathological diagnosis and treatment of azoospermia depend on precise identification of spermatogenic cells. Traditional methods are time-consuming and highly subjective due to complexity of Johnsen score, posing challenges for accurately diagnosing azoospermia. Here, we introduce a novel SC-YOLO framework for automating the classification of spermatogenic cells that integrates S3Ghost module, CoordAtt module and DCNv2 module, effectively capturing texture and shape features of spermatogenic cells while reducing model parameters. Furthermore, we propose a simplified Johnsen score criteria to expedite the diagnostic process. Our SC-YOLO framework presents the higher efficiency and accuracy of deep learning technology in spermatogenic cell recognition. Future research endeavors will focus on optimizing the model's performance and exploring its potential for clinical applications.

YOLO framework was optimized as SC-YOLO and applied to shape detection for automatic classification of spermatogenic cells in testicular pathology images.The SC-YOLO framework has high accuracy in identifying results from binomial distributions, with or without haploid germ cells.The SC-YOLO framework also has good performance in the identification of other types of pathological sections.

Alterations in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology.

STUDY QUESTION: How does the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology (ART) compare with the frequency of these mutations in control offspring conceived from spontaneous pregnancies? SUMMARY ANSWER: There is a slight increase in dynamic mutation instability in offspring conceived through ART compared with the naturally conceived offspring. WHAT IS KNOWN ALREADY: There is evidence to suggest that ART can increase the risk of birth defects and karyotypic abnormalities. However, the accumulating evidence of an association between ART and de novo genetic aberrations is controversial. STUDY DESIGN, SIZE, DURATION: A prospective clinical observational study was performed on 246 families recruited from an in vitro fertilisation (IVF) centre at a tertiary-care, university-affiliated teaching hospital from 2008 to 2012. The study included 147 ART families [75 IVF and 72 intracytoplasmic sperm injection (ICSI)] in the study group and 99 natural-conception families in the control group. PARTICIPANTS, SETTING, METHODS: Parental, umbilical cord and infant peripheral blood samples were collected, and the trinucleotide repeats of the ATN1, AR, ATXN1, ATXN3, Huntington, DMPK and FMR-1 genes were investigated between the generations; these genes were chosen due to their ability to undergo dynamic mutation. The frequencies and sizes of the mutational repeats, as well as the intergenerational instability, were measured. MAIN RESULTS AND THE ROLE OF CHANCE: In 2466 transmissions identified in the ART offspring, 2.11% (n = 52/2466) of the alleles were unstable upon transmission, while in the control group offspring, the frequency of dynamic mutation was 0.77% (n = 10/1300); this difference was statistically significant (P < 0.01). The unstable transmission alleles were detected in 32 (2.48%) of the 1288 alleles from the IVF offspring and in 20 (1.70%) of the 1178 alleles from the ICSI offspring; both of these frequencies were significantly different from that of naturally conceived offspring (0.77%) (P < 0.01 and P < 0.05, respectively). However, there were no significant differences in the sizes of the mutational repeats or in the rates of expansion or contraction among the three groups (P > 0.05). The repeat copy numbers of the examined genes were found to be within the normal ranges in all parents and infants. LIMITATIONS, REASONS FOR CAUTION: One strength of our study is the relatively large sample size; we were able to detect mutations in seven common dynamic genes, and this large sample size allowed us to detect unstable alleles. Although we observed a clear alteration in the frequency of dynamic mutation in the ART offspring compared with controls, further studies are urgently needed to confirm this observation and determine the cause of this phenomenon. WIDER IMPLICATIONS OF THE FINDINGS: DNA microsatellite analysis provides an important tool to assess genomic instability. In this study, we report an association between ART and the frequency of dynamic mutation. The instability could be a reflection of the core infertility problem, the controlled ovarian hyperstimulation and/or the in vitro culture conditions.

Clinical characteristics and treatment of azoospermia and severe oligospermia patients with Y-chromosome microdeletions.

Clinical characteristics, testicular pathology, serum levels of reproductive hormones, and genetic analysis were compared among 100 azoospermic, 20 oligozoospermic cases with azoospermia factor (AZF) microdeletion, and 50 fertile males to evaluate the relationship between the AZF microdeletion regions and the azoospermia phenotype. AZF microdeletion region, testicular volume, and serum reproductive hormone levels of patients were compared against histological examination of testicular biopsies. The number of cases of AZFa, AZFb, AZFc, AZFb + c, and AZFa + b + c microdeletion was respectively 2 (1.7%), 15 (12.5%), 77 (64.2%), 24 (20.0%), and 2 (1.7%). The testicular volume of patient with AZF microdeletion was smaller (P < 0.01), while luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were significantly higher than that of fertile individuals (P < 0.01 and P < 0.05, respectively). Among the patients, testicular volume with AZFb-microdeletion cases was larger compared to patients with AZFc or AZFb + c microdeletions (P < 0.05 and P < 0.01, respectively), whereas FSH levels were significantly lower than that of AZFc or AZFb + c microdeletions (P < 0.05). The Johnsen score of patients with an AZFb + c microdeletion was lower than that of patients with AZFb and AZFc microdeletions, but no significant difference was observed. Pathological findings of testicular biopsies poorly correlated with the pattern of AZF deletion, with the AZFc microdeletion exhibiting the most varied phenotypes. In subsequent assisted reproductive treatments, sperm from patients with an AZFc microdeletion that was obtained by testicular sperm aspiration (TESA) or microdissection testicular sperm extraction (m-TESE) were more likely to result in pregnancy. Combined with testis pathology pattern, the specific region of AZF microdeletion and hormonal assessments provide reliable prognostic information on the chance of successful sperm retrieval for assisted reproductive technologies.

The neural correlates of apathy in the context of aging and brain disorders: a meta-analysis of neuroimaging studies.

Introduction: Apathy is a prevalent mood disturbance that occurs in a wide range of populations, including those with normal cognitive aging, mental disorders, neurodegenerative disorders and traumatic brain injuries. Recently, neuroimaging technologies have been employed to elucidate the neural substrates underlying brain disorders accompanying apathy. However, the consistent neural correlates of apathy across normal aging and brain disorders are still unclear. Methods: This paper first provides a brief review of the neural mechanism of apathy in healthy elderly individuals, those with mental disorders, neurodegenerative disorders, and traumatic brain injuries. Further, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, the structural and functional neuroimaging meta-analysis using activation likelihood estimation method is performed on the apathy group with brain disorders and the healthy elderly, aiming at exploring the neural correlates of apathy. Results: The structural neuroimaging meta-analysis showed that gray matter atrophy is associated with apathy in the bilateral precentral gyrus (BA 13/6), bilateral insula (BA 47), bilateral medial frontal gyrus (BA 11), bilateral inferior frontal gyrus, left caudate (putamen) and right anterior cingulate, while the functional neuroimaging meta-analysis suggested that the functional connectivity in putamen and lateral globus pallidus is correlated with apathy. Discussion: Through the neuroimaging meta-analysis, this study has identified the potential neural locations of apathy in terms of brain structure and function, which may offer valuable pathophysiological insights for developing more effective therapeutic interventions for affected patients.

Effects of major depression and bipolar disorder on erectile dysfunction: a two-sample mendelian randomization study.

BACKGROUND AND AIMS: There are currently no clear conclusions about whether major depression (MD) and bipolar disorder (BD) increase the risk of erectile dysfunction (ED). In our study, we used a Mendelian randomization (MR) analysis to discover the causal associations between MD, BD and ED. METHODS: We got single-nucleotide polymorphisms (SNPs) related to MD, BD and ED from the MRC IEU Open genome-wide association study (GWAS) datasets. After a series of selection, SNPs left were selected as instrumental variables (IVs) of MD and BD for the following MR test to evaluate the relationship of genetically predicted MD or BD with the incidence of ED. Among them, we used the random-effects inverse-variance weighted (IVW) method as the main analysis. Finally, sensitivity analyses were further performed using Cochran's Q test, funnel plots, MR-Egger regression, Leave-one-out method and MR- pleiotropy residual sum and outlier (PRESSO). RESULTS: Genetically-predicted MD was causally related to the incidence of ED in the IVW methods (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.19-1.96; p = 0.001), while no causal impact of BD on the risk of ED (OR = 0.95, 95% CI 0.87-1.04; p = 0.306). The results of sensitivity analyses supported our conclusion, and no directional pleiotropy were found. CONCLUSION: The findings of this research found evidence of a causal relationship between MD and ED. However, we did not find a causal relationship between BD and ED in European populations.