Andrology最新文献

Background: Non-obstructive azoospermia (NOA) affects approximately 10% of infertile men and represents a major challenge in assisted reproductive technology (ART). A model that includes histological variants could be helpful in predicting sperm retrieval rate (SRR) after microdissection testicular sperm extraction (mTESE) in patients affected by NOA and without genetic abnormalities OBJECTIVES: To develop and validate a predictive nomogram integrating clinical and histopathological variables to estimate SRR in NOA patients undergoing microTESE.

Material and methods: A multi-center retrospective/prospective cohort study was conducted between 2022 and 2024, enrolling 333 men diagnosed with NOA across six academic centers. Preoperative data, including age, body mass index (BMI), hormonal profile (follicle-stimulating hormone [FSH], luteinizing hormone [LH], testosterone), genetic analysis, and ultrasound-measured testicular volume, were collected. MicroTESE was performed under microscopic guidance with histopathological evaluation. Predictive factors for successful sperm retrieval were analyzed through logistic regression, and a predictive nomogram was constructed and internally validated using bootstrapping techniques. Multi-variate logistic regression was performed to identify independent variables associated with SRR in patients with available final pathology. Therefore, a predictive nomogram was developed and validated using 1000 bootstrap samples.

Results: The overall SRR was 52.55%. Multi-variate analysis identified FSH levels (odds ratio [OR]: 0.97; p = 0.049), maturation arrest (OR: 0.04; p < 0.01), and Sertoli cell-only syndrome (SCOS; OR: 0.03; p < 0.01) as independent predictors of SRR. The predictive nomogram demonstrated good accuracy, with a C-index of 0.75, sensitivity of 73%, specificity of 82%, and overall accuracy of 77% at a cutoff of 0.33.

Discussion: Using preoperative and histology data, we developed a nomogram to predict SR outcomes in patients with NOA undergoing mTESE. Our findings demonstrate that integrating hormonal and histopathological data enhances predictive accuracy of the model, thus providing a valuable tool for preoperative counseling and clinical decision-making in couples presenting with infertility.

Conclusion: This validated nomogram effectively predicts sperm retrieval outcomes in NOA patients undergoing microTESE, facilitating improved patient counseling, informed clinical decisions, and optimized patient selection. Prospective external validation and further model refinement are recommended to enhance generalizability and clinical applicability.

Background: Microplastic pollution increasingly affects human health. Polystyrene nanoparticles (PS-NPs) and microplastics (PS-MPs) may impair Sertoli cells (SCs), vital for male fertility.

Objectives: To compare PS-NPs (80 nm)/PS-MPs (8 µm) toxicity on rat SCs, focusing on oxidative stress, apoptosis, epithelial barrier integrity, endocytosis pathways, and miRNA-mediated ceRNA networks.

Materials/methods: SCs viability was assessed via CCK-8. Trans-epithelial electrical resistance (TER) was measured to assess the epithelial barrier function. Particle internalization was evaluated by confocal microscopy and flow cytometry. Endocytosis was detected by using specific inhibitors. Whole-transcriptome sequencing profiling identified differential expression of miRNAs, lncRNAs, circRNAs, and mRNAs, with subsequent ceRNA network construction. Pro-inflammatory factors and apoptosis were detected by RT-qPCR and flow cytometry, respectively.

Results: At 100 µg/mL, PS-NPs reduced cell viability to 77% versus 94% for PS-MPs (p < 0.05) and decreased TER by 81% versus 63% for PS-MPs (p < 0.01). PS-NPs were internalized via clathrin- and caveolin-dependent pathways, while PS-MPs remained extracellular. RNA-seq revealed PS-MPs activated inflammation pathways (Ank3/Daxx), while PS-NPs triggered oxidative stress and apoptosis pathways (Map2k4/Grin2a). PS-NPs induced higher apoptosis (17% vs. 9.3%, p < 0.01), Reactive oxygen species (3.7-fold vs. 1.87-fold), and more severe catalase activity reduction (67% vs. 17%, p < 0.01) compared to PS-MPs.

Discussion and conclusion: PS-NPs pose greater toxicity to SCs than PS-MPs due to cellular internalization, disrupting barrier integrity via oxidative stress/apoptosis. PS-MPs primarily trigger extracellular inflammation. Distinct ceRNA networks underpin their differential mechanisms. These results highlight risks of environmental microplastic fragmentation into nanoplastics, emphasizing the need for further research on microplastic impacts on male fertility.

Objective: Thyroid hormones (THs) are critical in male reproductive physiology, but their associations with sperm parameters, particularly within the euthyroid range, remain controversial. This study aimed to investigate the relationships between free triiodothyronine (FT3), free thyroxine (FT4), and sperm quality, and evaluate the potential influence of thyroid autoimmunity (TAI).

Methods: This retrospective cohort study included 8478 men undergoing fertility consultation at the Third Affiliated Hospital of Zhengzhou University (April 2023-October 2024). Serum thyroid-stimulating hormone (TSH), FT3, FT4, thyroid antibodies, and semen parameters (volume, concentration, motility, morphology) were assessed. Participants were stratified into quartiles (Q1-Q4) based on FT3 and FT4 levels. Binary logistic and linear regression models, adjusted for potential confounding variables were used.

Results: In non-azoospermic men, higher FT3 quartiles associated with improved sperm motility (Q4 vs. Q1: progressive motility 39.2% vs. 35.0%, p < 0.001) and reduced midpiece defects (Q4:13% vs. Q1:15%, p < 0.001). Elevated FT3 levels were associated a decreased risk of asthenozoospermia (adjusted odds ratio [OR] for Q1:1.23, p = 0.010), whereas FT4 showed only weak associations with sperm concentration (p = 0.008). Among TAI-negative individuals, the prevalence of asthenozoospermia significantly decreased in the highest FT3 quartile (Q4:34.7% vs. Q1:42.6%, p < 0.001), but this trend was not observed in TAI-positive men. Linear regression revealed dose-dependent trends between FT3 and motility parameters (straight-line velocity [VSL], average path velocity [VAP], wobble [WOB]; all p < 0.05).

Conclusion: Although limited by its retrospective design, which could affect causal inference between THs and sperm parameters, this study demonstrated that TH levels, particularly FT3, showed significant associations with sperm motility and morphology, even within the euthyroid range. Furthermore, TAI status may potentially modulate TH effects on semen quality by some unidentified mechanisms. These findings supported that thyroid function screening should be provided for men with infertility and could help guide personalized endocrine interventions.

Background: Energy metabolism and substrate balance are critical determinants of sperm motility and fertility. Linear motility is necessary for sperm forward movement, whereas hyperactivated motility is a prerequisite for fertilization. The preference of metabolic pathways depends on substrate availability which controls sperm motility. However, there are differences in substrate composition in seminal plasma, vagina, uterus and oviducts.

Objectives: This study aims to clarify how the spermatozoa maintains its metabolic homeostasis and functions in the presence of glucose and lactate either alone or in combinations.

Materials and methods: Fresh bull spermatozoa was incubated with modified human tubal fluid (mHTF) medium containing either no-energy, glucose, lactate, or a combination of glucose and lactate. Sperm motility, kinematics, adenosine triphosphate (ATP) production, mitochondrial membrane potential, glucose incorporation, glycolysis, oxidative phosphorylation (OXPHOS), and acrosome reaction were systematically assessed.

Results: Glucose resulted in zigzag motility and lactate induced linear motility. Glucose-derived zigzag motility was suppressed by lactate with increasing lactate concentration in a dose-dependent manner. The addition of lactate with glucose showed higher mitochondrial membrane potential, higher oxygen consumption rate (OCR), and lower extracellular acidification rate (ECAR). Lactate suppressed glucose incorporation in midpiece and tail regions, reduced glycolysis, and shifted sperm metabolism toward OXPHOS which resulted in linear motility and maintained acrosome integrity.

Discussion: Lactate played a metabolic and regulatory role in bull sperm metabolism. As a metabolic role, it oxidized through OXPHOS and maintained linear motility. The metabolic changes by lactate suppressed glucose-induced acrosome reactions and maintained linear motility, which might be beneficial for sperm transportation toward the fertilization site of the female reproductive tract and results in successful fertilization.

Conclusion: This is a novel finding that explores the regulatory role of lactate over glucose metabolism in bull sperm functionality. Optimum balancing of glucose and lactate maintains the motility and functionality of bull spermatozoa. These outcomes might have substantial implications for the enhancement of sperm preservation techniques, sperm handling, and fertility outcomes.

YCT-529 reversibly reduces sperm counts to infertility levels in mice and non-human primates. Mice mating studies demonstrated 99% effectiveness in preventing pregnancies. YCT-529 has completed a first-in-class, double-blind, placebo-controlled Phase I clinical safety study in men and is currently being investigated in a Phase Ib/IIa clinical study.