OBJECTIVE: To observe the effects of the "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on key regulatory factors during mitochondrial apoptosis of testicular tissue in asthenozoospermia mice, and explore the potential mechanism of the protective effect of acupuncture on reproductive function. METHODS: Thirty C57BL/6 male mice were randomly divided into a blank group, a model group and an acupuncture group, 10 mice in each group. In the model and the acupuncture groups, the intraperitoneal injection of cyclophosphamide (30 mg•kg^-1•d^-1) was delivered for 7 days to prepare the asthenozoospermia model. After the success of modeling, the modeled mice in the acupuncture group were intervened with "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture, once daily and the needles were retained for 20 min. The duration of the intervention was 2 weeks. The general condition of each mouse was observed, and the body mass was recorded before modeling, after modeling and after intervention completion. After intervention, the testicular mass was recorded and the weight coefficient was calculated, and the mouse sperm quality was examined; the serum contents of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected using ELISA, the morphology of testicular tissue was observed using HE, the mitochondrial ultra-microstructure of testicular tissue was observed under transmission electrone microscopy, the mitochondrial membrane potential level of testicular tissue was detected using JC-1 staining, the positive rate of apoptosis cell of testicular tissue was observed using TUNEL; and the mRNA and protein expression of b-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (Cyt C), apoptotic protease-activating factor1 (Apaf-1), Caspase-9 and Caspase-3 of testicular tissue was detected using real-time quantitative fluorescence PCR and Western blot methods separately; and the positive expression of Cleaved Caspase-3 of the testicular tissue was detected using immunohistochemistry. RESULTS: Compared with the blank group, the mice were in listless spirits, had shaggy hairs, the reduced appetite and movement, and weight loss in the model group (P<0.01); the testicular mass and the weight coefficient decreased (P<0.01); the total number of sperms, sperm motility, and sperm viability were declined (P<0.01); while the levels of serum T, FSH, and LH were dropped (P<0.01). The morphology of seminiferous tubules in testicular tissue was abnormal, the number of spermatogenic cells and the number of mitochondria decreased, the inner mitochondrial crest was fractured and lost, and vacuoles appeared. The level of mitochondrial membrane potential was reduced (P<0.01); and the positive rate of apoptosis cell in testicular tissue increased (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was elevated (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 was dropped (P<0.01), and the average absorbance value of Cleaved Caspase-3 increased (P<0.01). When compared with the model group, in the acupuncture group, the general condition of mice was improved, the testicular mass and the weight coefficient elevated (P<0.01); the total number of sperms, sperm motility, and sperm viability increased (P<0.01); while the levels of serum T, FSH, and LH rose (P<0.01). The pathological morphology of testicular tissue and the inner mitochondrial ultra-microstructure were ameliorated, the level of mitochondrial membrane potential was elevated (P<0.01); the positive rate of apoptosis cell was reduced (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was dropped (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 elevated (P<0.05), and the average absorbance value of Cleaved Caspase-3 declined (P<0.01). CONCLUSION "Zhibian" (BL54)-toward- "Shuidao" (ST28) acupuncture may ameliorate mouse reproductive function by inhibiting mitochondrial apoptosis pathway, alleviating testicular tissue damage in the asthenospermia mice induced by cyclophosphamide.
Animals ; Male ; Mice ; Apoptosis ; Acupuncture Therapy ; Mitochondria/metabolism* ; Asthenozoospermia/genetics* ; Humans ; Testis/metabolism* ; Mice, Inbred C57BL ; Spermatozoa/metabolism* ; Acupuncture Points ; Sperm Motility ; Testosterone/blood* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Caspase 3/genetics* ; Follicle Stimulating Hormone/blood* ; Reproduction ; Cytochromes c/genetics* ; bcl-2-Associated X Protein/genetics* ; Apoptotic Protease-Activating Factor 1/genetics*

OBJECTIVE: To investigate the underlying mechanism of "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique for improving reproductive function in mice with asthenospermia by regulating ferroptosis pathway. METHODS: Sixty male C57BL/6 mice were randomly divided into a blank group, a model group, an acupuncture group and a Fer-1 group, 15 mice in each one. Except the blank group, the intraperitoneal injection with cyclophosphamide (50·kg^-1·d^-1) was administered to establish the asthenospermia model in the mice of the rest 3 groups for 5 consecutive days. In the acupuncture group, "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique was operated in the mice, for 20 min each time; and in the Fer-1 group, Fer-1 solution (1 mg/kg) was injected intraperitoneally. The interventions of these two groups were delivered once daily and for 2 consecutive weeks. The testicular wet weight was measured and the testicular coefficient was calculated. Using sperm quality detection system, the sperm quality was detected. With ELISA used, the contents of testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum were detected. With HE staining, testicular and epididymal morphology was observed. Immunofluorescence was used to detect the expression of reactive oxygen species (ROS) in the testes. Biochemical assay was conducted to determine the contents of malondialdehyde (MDA), reduced glutathione (GSH), and total iron ion (TFe) in the testicular tissue. Transmission electron microscopy was used to examine mitochondrial structure of the testis, while JC-1 staining was used to assess mitochondrial membrane potential in the testicular tissue. Fluorescence quantitative PCR and Western blot analyses were employed to measure the mRNA and protein expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the testicular tissue. RESULTS: Compared with the blank group, in the model group, the testicular wet weight and testicular coefficient decreased (P<0.01); the sperm concentration and sperm motility reduced (P<0.01), and the contents of T, FSH, and LH decreased in the serum (P<0.01); and the seminiferous tubules in the testis showed loose structure and deformed lumen, sperm cells were disorganized and the sperm numbers reduced; the tubular walls became thinner, and sperm numbers in the lumen less; the expression of ROS in testicular tissue, as well as the contents of MDA and TFe increased (P<0.01), and the content of GSH decreased (P<0.01); and the numbers of mitochondria reduced, the structure of cristae was serious damaged, and mitochondrial membrane potential level declined (P<0.01); the mRNA and protein expression of SLC7A11, GPX4, and FTH1 decreased (P<0.01), while the mRNA and protein expression of ACSL4 increased (P<0.01). In comparison with the model group, the acupuncture and Fer-1 groups showed the increase of testicular wet weight and coefficient (P<0.01), sperm concentration and motility (P<0.01), and the serum contents of T, FSH, and LH (P<0.01); and the improvements in testicular and epididymal histopathology; ROS expression and the contents of MDA and TFe decreased (P<0.01), and the content of GSH elevated (P<0.05); the mitochondrial structure and numbers were ameliorated and mitochondrial membrane potential rose (P<0.01). Besides, in comparison with the model group, the mRNA expression of SLC7A11 was higher (P<0.05, P<0.01), the mRNA and protein expression of GPX4 and FTH1 increased (P<0.01, P<0.05), and the mRNA and protein expression of ACSL4 decreased (P<0.01) in the acupuncture and the Fer-1 groups; and the protein expression of SLC7A11 was higher in the Fer-1 group (P<0.05). CONCLUSION "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique may improve the reproductive capacity in the mice with asthenospermia by alleviating ferroptosis-induced cellular damage and ameliorating testicular function.
Animals ; Male ; Ferroptosis ; Mice ; Acupuncture Therapy ; Mice, Inbred C57BL ; Asthenozoospermia/metabolism* ; Humans ; Acupuncture Points ; Testis/metabolism* ; Luteinizing Hormone/metabolism* ; Malondialdehyde/metabolism* ; Reproduction ; Testosterone/metabolism*

OBJECTIVE: To observe the effect of "Zhibian" (BL54)-to-"Shuidao" (ST28) needling technique on the reproductive function of the mice with poor ovarian response (POR) and explore the molecular mechanism of acupuncture on early embryos after in vitro fertilization-embryo transfer (IVF-ET) in POR mice. METHODS: Of 70 female C57BL/6 mice, 60 mice with regular estrous cycle were screened and 30 of them were randomly divided into a blank group, a model group, and an acupuncture group, 10 mice in each one. Mice in the model and acupuncture groups were administered with tripterygium glycosides suspension (50 mg·kg^-1·d^-1) via gavage for 2 weeks to prepare POR models; while in the blank group, the mice received an equal volume of 0.9% sodium chloride solution via gavage. After successful modeling, mice in the acupuncture group underwent "Zhibian" (BL54)-to-"Shuidao" (ST28) needling technique, once daily, for 20 min each time and lasting 2 consecutive weeks. After intervention completion, subsequently, all the three groups underwent ovulation induction, orbital blood collection, and ovary extraction and fresh denuded oocyte collection. Denuded oocytes, after incubated, together with the sperms from 15 male C57BL/6 mice, were transferred into the oviducts of 30 donor pseudopregnant C57BL/6 female mice via IVF-ET; and the embryonic tissue was collected on day 7 of implantation. After successful modeling and intervention completion, the general conditions of mice in each group were observed, and the estrous cycle disorder rate was compared among the groups. After intervention completion, the numbers of oocyte, ovarian wet weight and ovarian index were recorded in each group; the levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in the serum were measured using ELISA; and ovarian morphology and mitochondrial ultrastructure were examined using HE staining and transmission electron microscopy. The transcriptome sequencing technology was employed to identify differentially expressed genes (DEGs) in early embryos of each group, followed by bioinformatics analysis; and the reversed DEGs with significant difference were verified using quantitative real-time PCR (qRT-PCR). RESULTS: After intervention, compared with the blank group, the mice in the model group presented poor spirits and declined water and food intake, reduced activity, the higher rate of estrous cycle disorder (P< 0.01); the decrease of the numbers of oocyte, ovarian wet weight, and ovarian index (P<0.01), reduced AMH and E2 in the serum (P<0.01), elevated FSH and LH in the serum (P<0.01); more atresia follicles in ovarian tissue, disorganized granulosa cells, reduced the numbers of mitochondria, vacuoles appeared and cristae breakage. When compared with the model group, in the acupuncture group, the spirits of mice, food intake and activity were improved, the rate of estrous cycle disorder was reduced (P<0.01); the numbers of oocyte, ovarian wet weight, and ovarian index were higher (P<0.01, P<0.05), the levels of AMH and E2 in the serum increased (P<0.01), the levels of FSH and LH in the serum decreased (P<0.01); the atresia follicles were reduced, the numbers of follicle increased at all levels, the numbers of mitochondria got higher, vacuoles and cristae breakage were declined. In comparison between the blank group and the model group, and between the model group and the acupuncture group, a total of 258 intersecting DEGs were identified, and 194 DEGs of them exhibited a trend of reversion before and after intervention. The top 5 reversed DEGs with significant difference included dexamethasone-induced Ras-related protein 1 (Rasd1), gene regulated by estrogen in breast cancer 1 (Greb1), leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6), Fraser syndrome 1 (Fras1), and apolipoprotein D (Apod). Compared with the blank group, the mRNA expression of Rasd1, Greb1, Lgr6, Fras1 and Apod in embryonic tissues decreased in the model group (P<0.01, P<0.05); and when compared with the model group, the mRNA expression of Rasd1, Greb1, Lgr6, Fras1 and Apod in embryonic tissues increased in the acupuncture group (P<0.05, P<0.01). These findings were consistent with the DEGs screening results. Gene ontology (GO) analysis revealed that the reversed genes of co-expression were primarily participated in the biological processes such as myoblast differentiation, endocardial cushion development, and cardiac morphogenesis. Kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that the reversed genes of co-expression are enriched in the Wnt signaling pathway, and they were associated with various types of cardiac diseases. CONCLUSION The "Zhibian" (BL54)-to-"Shuidao" (ST28) needling technique may ameliorate the decline of ovarian response in mice with POR, promote normal follicle development and ovulation, thereby improve embryo quality and reduce the risk of developmental defects and deformity in the organs such as the embryonic heart. The underlying mechanism may be related to the regulation of the expression pattern of embryonic key genes through the Wnt signaling pathway.
Animals ; Female ; Mice ; Mice, Inbred C57BL ; Acupuncture Therapy ; Ovary/physiopathology* ; Humans ; Fertilization in Vitro ; Transcriptome ; Embryo Transfer ; Infertility, Female/physiopathology*

OBJECTIVE: To observe the effects of electroacupuncture (EA) with different frequencies on spermatogenic function, testicular morphology and oxidative stress in oligoasthenospermia (OAT) rats, and to explore the mechanism and the optimal parameters of EA for OAT. METHODS: Sixty SPF-grade male SD rats were randomly divided into a solvent control group, a model group, a 2 Hz EA group, a 100 Hz EA group and a 2 Hz/100 Hz EA group, with 12 rats in each group. Except for the solvent control group, the other 4 groups were administered ornidazole suspension (800 mg·kg^-1·d^-1) by gavage for 28 d to establish the OAT model. Starting from the 1st of modeling, EA was applied at "Guanyuan" (CV4), "Qihai" (CV6) and bilateral "Sanyinjiao" (SP6) and "Zusanli" (ST36) in the 3 EA groups, continuous wave of 2 Hz, continuous wave of 100 Hz, and disperse-dense wave of 2 Hz/100 Hz were used in the 2 Hz EA group, the 100 Hz EA group, and the 2 Hz/100 Hz EA group, respectively, with current intensity of 1-3 mA, 30 min a time, once every other day, for 28 consecutive days. After intervention, the testicular index was calculated, epididymal sperm quality was assessed, and the fertility ability was observed; morphology of testicular tissue was observed by HE staining, and the Johnson score was calculated; the positive expression of reactive oxygen species (ROS) in testicular tissue was detected by immunofluorescence; the activity of superoxide dismutase (SOD) and catalase (CAT), as well as the level of malondialdehyde (MDA) in testicular tissue were measured by ELISA; the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in testicular tissue was detected by Western blot. RESULTS: Compared with the solvent control group, in the model group, the testicular index, sperm concentration, sperm motility and the number of offspring were decreased (P<0.01), the seminiferous tubules atrophied and the Johnson score decreased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were decreased (P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were increased (P<0.01). Compared with the model group, in the 2 Hz EA group, the 100 Hz EA group and the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility and the number of offspring were increased (P<0.05, P<0.01), the pathological morphology of testicular tissue improved and the Johnson scores increased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were increased (P<0.05, P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were decreased (P<0.05, P<0.01). Compared with the 2 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility, as well as the CAT activity and HO-1 protein expression in testicular tissue were increased (P<0.01, P<0.05); the positive expression of ROS was decreased (P<0.01). Compared with the 100 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index was increased (P<0.01), the positive expression of ROS in testicular tissue was decreased (P<0.01). CONCLUSION EA with 2 Hz continuous wave, 100 Hz continuous wave, and 2 Hz/100 Hz disperse-dense wave can all improve the spermatogenic arrest and reduce the level of oxidative stress in testicular tissue in OAT rats, the mechanism may be related to up-regulating the protein expression of Nrf2 and HO-1 and improving oxidative stress. EA with disperse-dense wave of 2 Hz/100 Hz shows the optimal effect.
Male ; Animals ; Electroacupuncture ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; Oligospermia/genetics* ; Humans ; Testis/metabolism* ; Superoxide Dismutase/metabolism* ; Asthenozoospermia/genetics* ; Acupuncture Points ; Malondialdehyde/metabolism*

OBJECTIVE: To observe the clinical efficacy of warming acupuncture combined with western medication for oligoasthenoteratozoospermia of kidney-yang insufficiency and its effects on the levels of interleukin (IL)-6 and IL-10 in seminal plasma. METHODS: A total of 60 patients with oligoasthenoteratozoospermia of kidney-yang insufficiency were randomly divided into a combination group and a medication group, with 30 cases in each group. The medication group was treated with levocarnitine oral solution orally, 10 mL once, 3 times a day. On the basis of the treatment in the medication group, warming acupuncture was applied at Baihui (GV20), Guanyuan (CV4) and Mingmen (GV4) in the combination group, once every other day, 3 times a week. Both groups were treated for 12 weeks. Before and after treatment, the TCM syndrome score was observed, the semen routine indexes (the sperm concentration, progressive [PR] sperm motility, PR + non-progressive [NP] sperm motility and sperm malformation rate), the serum sex hormones indexes (follicle-stimulating hormone [FSH], luteinizing hormone [LH], testosterone [T] and estradiol [E₂]), as well as the IL-6 and IL-10 levels in seminal plasma were detected, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, except for the hyposexuality score in the medication group, the each item scores and total scores of TCM syndrome were decreased compared with those before treatment (P<0.01, P<0.05), the sperm malformation rates, serum FSH and LH levels, IL-6 levels in the seminal plasma were decreased compared with those before treatment (P<0.01, P<0.05), the PR sperm motility, PR + NP sperm motility, serum T levels, IL-10 levels in the seminal plasma were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the sperm concentration was increased compared with that before treatment in the combination group (P<0.01). After treatment, compared with the medication group, except for the hyposexuality and frequent nocturia scores, the each item scores and total score of TCM syndrome were lower (P<0.01, P<0.05); the sperm concentration, PR sperm motility and PR + NP sperm motility, serum T level, IL-10 level in the seminal plasma were higher (P<0.01, P<0.05); sperm malformation rate, serum FSH and LH levels, IL-6 level in the seminal plasma were lower (P<0.01, P<0.05) in the combination group. The total effective rate was 83.8% (25/30) in the combination group, which was superior to 60.0% (18/30) in the medication group (P<0.05). CONCLUSION Warming acupuncture combined with western medication can effectively treat oligoasthenoteratozoospermia of kidney-yang insufficiency, regulate the levels of sex hormones, and its mechanism may be related to the down-regulation of IL-6 level and the up-regulation of IL-10 level in seminal plasma.
Humans ; Male ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Adult ; Semen/metabolism* ; Acupuncture Therapy ; Oligospermia/drug therapy* ; Yang Deficiency/physiopathology* ; Kidney/physiopathology* ; Young Adult ; Asthenozoospermia/drug therapy* ; Combined Modality Therapy ; Treatment Outcome

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

BACKGROUND: Infertility is a burdensome, often overlooked condition. This study aimed to investigate the global distribution and trends in the burden of infertility from 1990 to 2021. METHODS: We obtained data on the prevalence and years lived with disability (YLDs) related to infertility from the Global Burden of Disease 2021 study and evaluated them by calculating the estimated annual percentage change in age-standardized rates. We investigated the relationship between sociodemographic index (SDI) and the burden of infertility on the global, regional, and national levels. RESULTS: In 2021, there were 143,261,562 female and 55,481,380 male infertility cases worldwide, respectively. In China, female and male infertility cases accounted for 23.59% and 21.47% of the global totals, reaching 33,795,944 and 11,909,889, respectively. Compared with 2019, the global number of female and male infertility cases increased by 5,286,227 in females and 2,017,271 in males. In contrast, China saw a decline in both female and male infertility cases, with reductions of 698,735 and 154,591, respectively. From 1990 to 2021, the age-standardized prevalence rate (ASPR) and age-standardized YLDs rate (ASYR) for female infertility both increased by 0.59% annually, whereas these two corresponding indicators for male infertility increased by 0.50% annually worldwide. The burden of female infertility was consistently higher than that of male infertility and demonstrated a faster rate of increase. East Asia had the highest ASPR and ASYR for female infertility, whereas Eastern Europe had the highest metrics for male infertility. A horizontal S-shaped association was observed between the SDI and ASPR and ASYR of infertility, with a rapid decline in the infertility burden when the SDI exceeded 0.7. CONCLUSIONS The global burden of infertility has increased over the years, with a higher burden on women and underdeveloped regions. These findings emphasize the need to prioritize healthcare for patients with infertility to address the rising burden.
Humans ; Female ; Male ; Global Burden of Disease ; Prevalence ; Infertility/epidemiology* ; Adult ; Infertility, Male/epidemiology* ; Persons with Disabilities/statistics & numerical data* ; Middle Aged ; Infertility, Female/epidemiology* ; China/epidemiology* ; Disability-Adjusted Life Years

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

Testicular tumor is the most common solid malignancy in males under 40 years of age. This malignancy is known to have a negative impact on male fertility. Therefore, several techniques for sperm retrieval have been proposed, including microdissection testicular sperm extraction (mTESE). The objective of this study was to review the literature on the outcomes of oncological (Onco)-mTESE at the time of radical orchiectomy. We conducted a comprehensive literature search through PubMed, Scopus, and Cochrane Central Controlled Register of Trials. Only studies reporting ex vivo mTESE in patients with testicular tumor were considered. Twelve papers met the inclusion criteria and were included in this review. Tumor size was identified as the sole preoperative factor influencing spermatogenesis. The considered studies demonstrated a satisfactory success rate for Onco-mTESE, associated with a similarly valid percentage of live healthy births through assisted reproductive technology. Currently, no comparison has been made between Onco-mTESE and conventional Onco-TESE, hence further assessment is required. In cases where the tumor completely replaces the cancer-bearing testicle, a contralateral micro-TESE may be a viable alternative. However, the surgeon should evaluate associated risks and benefits preoperatively. In conclusion, Onco-mTESE at the time of radical orchiectomy appears to be a promising therapeutic option for young patients with testicular tumors. Nevertheless, additional studies are necessary to achieve a definitive conclusion.
Humans ; Male ; Azoospermia/etiology* ; Sperm Retrieval ; Orchiectomy/methods* ; Testicular Neoplasms/complications* ; Microdissection/methods* ; Testis/surgery* ; Adult

Discovery of spermatozoa during the 17 th century led to developing technologies for semen analysis in the early 1900s, and then, standard techniques were implemented during the 20 th century. Semen analysis has a pivotal role in the male infertility evaluation, and azoospermia is an important finding. Azoospermia is identified in 15% of infertile men. However, the accurate laboratory assessment of azoospermia poses certain technical challenges. Laboratories currently perform semen assessment with great variability; thus, a standard method should be used. Planning suitable management and determining the cause of infertility require a precise evaluation of azoospermia. This review aims to address the definition of azoospermia and highlight laboratory methods in the assessments of azoospermia. Basic methods such as centrifugation, repeat pellet analysis, and staining and advanced methods such as genetic testing and biomarkers have been discussed. These methods have helped in standardizing the protocol for accurate azoospermia assessments with less variability.
Humans ; Azoospermia/genetics* ; Male ; Semen Analysis/methods* ; Andrology/methods*