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In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress. [ABSTRACT FROM AUTHOR]

I read the recent paper published in the I Andrologia i titled 'Effect of varicocele on sperm DNA damage: A systematic review and meta-analysis' by Zhang et al. (2022). In this study, the authors concluded that 'In conclusion, patients diagnosed with clinical varicocele had higher DNA fragmentation índex than healthy controls, which means varicocele could impair sperm DNA, consequently the fertility potential of affected men'. Certainly, such information would contribute to better understand if, and to what extent, varicocele induces cyto- and/or genotoxicity in sperm cells as a result of DNA fragmentation in sperm cells. [Extracted from the article]

Varicocele is a main cause of lower production of spermatozoon and infertility with multiple pathophysiological mechanisms. In the past decades, the use of dietary supplements has significantly increased due to both the modern lifestyle and the food shortages of the industrialised countries. The purpose of this review paper is to collect scientific evidences from basic and clinical studies which support the use of dietary supplements to define the clinical framework for patients with varicocele. In the present review, we used keywords such as dietary supplements, varicocele, male infertility, oxidative stress, DNA fragmentation, sperm parameters to find the proper articles. The standard search biomedical engines were used for seeking the papers. The use of dietary supplements such as minerals, vitamins and antioxidants has an essential role in the prevention and treatment of varicocele by increasing the levels of antioxidant enzymes (e.g. peroxidase, superoxide dismutase and catalase) and decreasing the levels of inflammatory markers (e.g. tumour necrosis factor‐α, interleukin‐6 and interleukin‐1) in testis. According to the results, the dietary supplements may alleviate the spermatogenesis in varicocele patients through different mechanisms such as suppression of stress oxidative and inflammation in testicular tissue. [ABSTRACT FROM AUTHOR]

Varicocele is the primary cause of male infertility and the interests of research about varicocele have changed in the last years. The aim of the study was to analyse how topics of interests about varicocele have changed in the last two decades. Literature about paediatric varicocele between 2000 and 2018 was reviewed, and the subjects of the articles were analysed, selecting the main and secondary topics of each article. A study of their prevalence over the years was performed. In the research, 625 articles were found but only 169 provided data in the paediatric age. The total percentage of exclusively paediatric works was 27.04%, being above average in Europe, North and South America. The main subject both for Europe and North America was surgical technique, while for Asia it was videolaparoscopy. The main issue in South America was fertility; Africa and Oceania do not have enough publications to make statistics. Paediatric articles account for less than one‐third of overall articles. The first interest of research is surgical technique. In Europe, the topics seem to exclude fertility potential. [ABSTRACT FROM AUTHOR]

The primary goal of this systematic review and meta‐analysis was to compare the efficacy and safety of fluoxetine with other oral pharmaceuticals in the treatment of premature ejaculation (PE). We searched through databases including CNKI, PubMed, EMBASE and Cochrane to find research published up to 31 March 2022. PROSPERO was used to pre‐register this meta‐analysis (registration number CRD42022315459). Two separate writers extracted relevant details from all of the papers included in the study. To analyse the quality of literature publishing, we used the Cochrane risk of bias tool. The severity of premature ejaculation was determined using intravaginal ejaculatory latency time (IELT), and the effectiveness and safety of pharmacological interventions were determined using standardized mean difference (SMD) and risk ratio (RR) values with matching 95% confidence level intervals (95% CIs). Our meta‐analysis includes a total of ten trials to investigate into the differences in treatment efficacy and safety between fluoxetine and other medicines. The findings revealed that fluoxetine was more effective than placebo in treating PE, whereas sertraline and paroxetine were more effective than fluoxetine (p < 0.05). The side effects of the medications were not significantly different, and they were all acceptable. The results of the sensitivity analysis were unaffected by the removal of any of the articles. There was no evidence of bias in the media. This meta‐analysis examined the differences in efficacy and safety between fluoxetine and other oral medications and can be used by clinicians in the treatment of PE. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common tumours in adult men and heat shock proteins play an important biological function in prostate cancer as molecular chaperones involved in the pathogenesis, diagnosis, treatment and prognosis of a wide range of tumours. Among them, increased expression of HSP90, a member of the heat shock protein family, is associated with resistance to prostate cancer denervation and can promote tumour resistance, invasion and bone metastasis, thus making prostate cancer more difficult to treat. Therefore, targeting HSP90 in prostate cancer could be a promising strategy for oncology treatment. This paper reviews the structure and function of HSP90, HSP90‐mediated denudation resistance in prostate cancer and HSP90‐targeted antitumor therapy, with the aim of providing a new theoretical basis for prostate cancer treatment options in the clinical setting. [ABSTRACT FROM AUTHOR]

Many approaches have been examined to reversing multidrug resistance (MDR), but sub‐optimal target‐based strategies have limited their efficacy. Herein, we investigate microRNA (miR‐21) suppression on the doxorubicin (DOX)‐sensitisation of the DOX‐resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR‐21, P‐glycoprotein (P‐gp), MDR‐1 and PTEN evaluated in PC3/DOX cancer cells by qRT‐PCR and western blot analyses. The cytotoxic effects of transfected of miR‐21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P‐gp. Apoptosis was detected by Flow cytometry. As expected, miR‐21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA‑21 suppression considerably hindered PC3/DOX cell viability. miR‑21 suppression dramatically downregulated P‐gp expression and activity in DOX‐resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P‐gp cascade, which miR‐21 suppression led to the upregulation of PTEN and sequentially lower‐expression of P‐gp that reversed MDR. Also, miR‐21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR‐21 in MDR‐reversing in PCa. [ABSTRACT FROM AUTHOR]

Male fertility preservation has been steadily increasing over the past two decades. Significant improvements have been achieved in the treatment modalities of cancer and other severe chronic medical conditions, leading to an increase in patient survivorship and the resulting demand for future parenthood. Recognition and proper patient counselling before commencing therapies with a potential gonadotoxic effect are of paramount importance. Similarly, nonmedically indicated fertility preservation is on the rise. Social sperm banking, gender dysphoria prior to affirmation procedures and posthumous reproduction preservation are becoming more common. When timing and logistics are appropriate, sperm cryopreservation is considered the gold standard for fertility preservation. Testicular tissue and spermatogonial stem cell autotransplantation is considered experimental and represents a promising alternative for pre‐pubertal patients. The current paper aims to review the recent trends in male fertility preservation, the common indications for sperm cryopreservation, techniques for sperm retrieval and experimental frontiers. [ABSTRACT FROM AUTHOR]

The main purpose of this methodological paper was to describe a recently designed one‐step ICSI semen preparation swim‐out method (called swim‐ICSI) and to compare its efficacy with our conventional two‐step swim‐out method for the selection of motile spermatozoa for ICSI with minimal DNA damage. In this observational cohort study, 42 fresh ejaculate sperm samples for ICSI were included to compare the new swim‐ICSI with the conventional swim‐out. In a sub‐analysis (n = 20), both in‐house designed ICSI preparation methods were compared with a commercial magnetic‐activated cell sorting test (MACS®). Sperm DNA fragmentation (SDF), using Halosperm®, was determined at different time points during sperm preparation: on the native sample (a), after density gradient centrifugation (DG) (b), on the motile (A + B) spermatozoa selected with conventional swim‐out post‐DG (c) and selected with swim‐ICSI method post‐DG (d). For a subgroup (n = 20), SDF was also calculated after MACS (e). The mean SDF significantly reduced after EACH preparation step and reduced to almost zero in the recovered A + B spermatozoa when the semen prepared with DG was further processed for ICSI (swim‐ICSI vs. swim‐out, p =.001). In conclusion, the optimised one‐step and fine‐tuned swim‐ICSI technique shows the possibility to select a population of spermatozoa with almost zero SDF to be used in ICSI treatments. [ABSTRACT FROM AUTHOR]

Male factor accounts for about 30–50% of infertility. A common cause of male infertility is drug abuse; either illicit or prolonged use of prescribed drugs. This study provides a review of the physiology of the hypothalamic–pituitary–gonadal axis and recent literature on drugs that have been linked to male infertility and the associated mechanisms. Relevant peer‐reviewed papers were assessed online using PubMed/PubMed Central, Scopus, AJOL, Google Scholar and DOAJ databases using Medical Subjects Headings (MeSH) indexes and relevant key word searches. Although drugs are beneficial when used at therapeutic levels, the abuse leads to impairment of hypothalamic–pituitary–gonadal functions, increased sperm DNA fragmentation and apoptosis, and reduced sperm quality. A good knowledge of the physiology of the hypothalamic–pituitary–gonadal axis and the influence of drugs on male fertility will guide healthcare providers in managing cases of infertility. [ABSTRACT FROM AUTHOR]

It was with interest and surprise that we read the Letter to the Editors regarding our review paper entitled "The role of infections and leukocytes in male infertility" (Henkel et al., 2020). Although the authors start their correspondence by referring specifically to causal effects of inflammation of the MGT to male infertility, it is important to note that the authors here are postulating the use of VNS to improve male fertility and not male infertility. In fact, it has long been known that after idiopathic infertility and varicocele, MGT infections with about 11.6% are the third single most cause of male infertility (Henkel, 2020; Nieschlag & Behre, 1997), and it is generally accepted that these infections are potentially correctable (Weidner et al., 1999). [Extracted from the article]

In our investigation of the work of Dr Safarinejad, we found one RCT published in Andrologia on the treatment of premature ejaculation (Mohammad Reza Safarinejad, [6], [7]; Safarinejad & Hosseini, [3]). Safarinejad ([8]) (Safarinejad, [7]; Safarinejad & Hosseini, [8]) (table on the left) was published in the I International Journal of Impotence Research i in August 2006 and included 58 men with premature ejaculation randomized to receive citalopram or placebo. Recently we became aware of eight retracted randomized clinical trials (RCTs) authored by Dr MR Safarinejad from Shahid Beheshti University, Tehran, Iran (Mohammad R Safarinejad, [5]; Mohammad Reza Safarinejad, [10], [11]; Mohammad Reza Safarinejad, [12], [13]; Mohammad Reza Safarinejad et al., [14]; Mohammad Reza Safarinejad et al., [15]). Safarinejad ([3]) (Safarinejad, [7]; Safarinejad & Hosseini, [8]) (table on the left) was published in the I International Journal of Impotence Research i in August 2006 and included 58 men with premature ejaculation randomized to receive citalopram or placebo. [Extracted from the article]

Zinc is proposed to have an important role in the morphology, viability and motility of spermatozoa. There are inconsistent reports on the association between seminal plasma zinc concentration and male infertility. For this purpose, papers reporting the level of seminal zinc among asthenozoospermic groups were selected and used for further analysis. This meta-analysis of previous published studies was performed to obtain more precise information on the association between seminal plasma zinc and asthenozoospermia. Relevant studies for inclusion were identified after preliminary investigation of research papers published on electronic databases up to February 2015. Eight reports and 475 subjects were finally included in the meta-analysis. In the overall analysis, a statistically significant reduction in seminal plasma zinc concentrations was observed in asthenozoospermic infertile men. Random-effects method was used to evaluate the summary effect size due to the presence of significant heterogeneity. The effect of zinc on asthenozoospermia was significant (Hedge's G effect size = −0.506, 95% confidence interval (95% CI): −0.998 to −0.014, P = 0.044). Taken together, despite of significant statistical heterogeneity between studies, our findings were indicative of significant association between zinc concentration and asthenozoospermia. In conclusion, the meta-analysis suggests that seminal plasma zinc concentration is negatively associated with male infertility. [ABSTRACT FROM AUTHOR]

Infertility is a multiplex disorder in the reproductive system, and men are responsible for more than half of the cases. Nowadays, semen analysis has been considered the critical assessment test to diagnose infertile men; however, it has limitations so that the cause behind infertility in 40% of infertile men is unrevealed. Weaknesses of semen assessment indicate a global need for novel and better diagnostic tools and biomarkers. MicroRNAs are short (about 18-- 22 nucleotide length) non- coding RNAs that control most (>60%) of our protein- coding genes post- transcriptionally. These molecules are aberrant in the body fluids, and abnormal alterations in their expression level can signify a specific disease such as infertility. Therefore, microRNAs can be novel candidate biomarkers that can diagnose different types of male infertility, including azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. This narrative review aimed to collect and sum up new papers published about the significant role of microRNAs in different male infertility categories. [ABSTRACT FROM AUTHOR]

Our purpose was to review and analyse the impact of pyrethroids and organophosphates exposure on human semen parameters. A comprehensive literature search was performed through MEDLINE via PubMed, Scopus and Webscience. Only cohort studies examining semen parameters in workers or general populations exposed to pyrethroids or organophosphates were included. Ejaculate volume, sperm count, concentration, motility, viability, normal morphology and seminal pH alterations were pooled using the Cochran–Mantel–Haenszel Method with the random effect model and expressed as weighted mean difference, risk ratios, 95% confidence intervals and p‐values. Seven cross‐sectional studies regarding pyrethroids were included. Four of them were eligible for meta‐analysis. The only parameter affected by pyrethroid exposure was normal sperm morphology (WMD‐7,61%, 95%CI –11,92 to −3,30;p = 0,0,005). Nine studies were selected to evaluate the impact of organophosphates on semen parameters with six of them eligible for meta‐analysis. A significant reduction was detected for the following: ejaculate volume (WMD −0,47ml, 95%CI −0,69 to −0,25; p < 0,0001), sperm count (WMD‐40,03, 95%CI −66,81 to −13,25;p = 0,003), concentration (WMD‐13,69 x10⁶/mL, 95%CI −23, 27 to‐4,12;p = 0,005) and motility (WMD −5,70%, 95%CI −12,89 to 1,50;p = 0,12). Despite the increase in sperm abnormality, it has been shown that pyrethroids are unrelated to reduced sperm quality. However, the negative association of organophosphates with spermatogenesis is noteworthy. [ABSTRACT FROM AUTHOR]

The present opinion paper, explores the possibility that optimal hormone treatment and judicious nutraceutical food supplement can help ageing men to gain quality-adjusted life years. Testosterone treatment of patients with late-onset hypogonadism is given via the transdermal route or by intramuscular injections. There is overwhelming evidence that testosterone replacement therapy ( TRT) has many beneficial effects and increases longevity by approximately 2% per year. On the basis of knowledge of physiology, animal and human experimental data, we explain why TRT reduces the risk of cardiovascular disease and of prostate cancer. However, the total testosterone load supplied per day should remain within the physiological range, and new galenical formulations should be developed, mimicking normal day-night variations. [ABSTRACT FROM AUTHOR]

Numerous studies concentrate on the association between X‐ray repair cross‐complementing group 1 (XRCC1) gene polymorphism and male infertility; however, the results remain inconclusive and inconsistent. Hence, this meta‐analysis was conducted to get a precise estimation of the correlation. PubMed, Web of Science, Embase, Scopus and China National Knowledge Infrastructure (CNKI) databases were searched to identify the all relevant studies before 3 May 2020. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association. Finally, six studies with 1,886 cases and 1,212 controls were included in our study. The result indicated that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility under allelic model (A‐allele vs. G‐allele: OR = 1.183, p =.003), heterozygote genetic model (AA vs. GA: OR = 1.256, p =.027), recessive genetic model (AA vs. GG + GA: OR = 1.279, p =.012) and dominant genetic model (AA + GA vs. GG: OR = 1.218, p =.026). In addition, in Asian subgroup, statistic correlation remained significant in allelic model (A‐allele vs. G‐allele: OR = 1.145, p =.025) with rare heterogeneity (I2 = 0%). In summary, our meta‐analysis suggested that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility and the A‐allele might be a risk factor for this disease, especially in Asians. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumours ( TGCT) represent 1%-1.5% of all male neoplasms, and they have the highest prevalence among men between 15 and 35 years old. Synchronous bilateral disease is a rare presentation, and the ratio of metachronous to synchronous bilateral disease is about 4 : 1. Several studies have suggested a correlation between male infertility and testicular cancer, with a 20-fold increase in the incidence of testicular cancer in infertile patients compared with the general population. At the time of diagnosis, 50%-75% of patients with unilateral TGCT present with subfertility; almost 13% of the patients are azoospermic before treatment, and up to two-thirds of patients become azoospermic following adjuvant cancer therapies. Therefore, fertility preservation should be considered in all oncological treatments. The only available option to preserve the reproductive potential in azoospermic patients with testicular cancer is to perform an onco-testicular sperm extraction (onco- TESE) before cancer treatment. In this paper, we describe a rare case of a patient with synchronous bilateral testicular cancer and azoospermia who was submitted to onco- TESE, sperm cryopreservation, and which was followed by the delivery of a healthy baby after intracytoplasmic sperm injection ( ICSI), emphasising the importance of fertility preservation in oncology patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to pair of dicentric Y-chromosomes in the previous issue.

While self-report screening instruments are highly sensitive to hypogonadism in the ageing male, they have lacked specificity as evidenced by low or absent correlations with testosterone. The purpose of this paper was to develop an economical and specific screening instrument for identifying hypogonadal ageing men. Based on a comprehensive study of physical, somatoform and affective complaints, sexual behaviour and function and hormonal parameters of 263 outpatients aged 40 years and above (M = 56.2; 40–84 years) recruited from six andrological outpatient departments in Germany, we identified those items correlating significantly with testosterone. By factor analyses, five factors were identified: ‘reduced activity’, ‘dissatisfaction with sexual function’, ‘negative self-concept of physical fitness’, ‘reduced sexual desire’ and ‘hot flushes’. The corresponding scales were reliable and only moderately inter-correlated. Consistent correlations were found with the level of testosterone, ageing male scales (Androgen Deficiency in the Aging Male, Aging Male Survey), specific affective, somatoform and sexual functioning scales and potential determinants of low testosterone (body mass index, physical inactivity, etc.). While further validation is needed, the new Hypogonadism Related Symptoms Scale appears to be a promising hypogonadism screening tool. [ABSTRACT FROM AUTHOR]

Observational studies, sometimes, can not provide us with clear answers for very important questions. The answer for a question on whether sex hormones in general, and oestrogen in particular, play some role in inducing and development of Crohn’s disease is uncertain. Study design, inclusion criteria, and different formulations of oral contraceptives may partly explain the conflict results of the published reports. But these may be due to the divergent effects of oestrogen, which are based on dose, tissue specificity and cellular environment. This paper is aimed at examining the influence of androgens on the prognosis of Crohn’s disease. [ABSTRACT FROM AUTHOR]

Men perceive a bloody ejaculate as an alarming physical symptom and often seek the help of urologists for explanation and treatment. After a complete urological step-by-step examination including imaging studies and flexible cystoscopy, malignancy or another significant disease can be ruled out in the majority of cases. However, many of these cases of haematospermia may still remain idiopathic and thus unsatisfactory for both the patient and his physician. The following paper reviews the aetiology, the diagnostic work-up escalation and the treatment options of haematospermia. [ABSTRACT FROM AUTHOR]

Ethyl methanesulphonate (EMS) is a mutagenic alkylating agent that induces marked elevations of sperm abnormalities in mice. In this paper, we report the ultrastructural findings on the morphology of the seminiferous epithelium of mice resulting from EMS administration. Eight- to twelve-weeks-old male mice were injected intraperitoneally with EMS at 200 mg kg−1 body weight daily for five consecutive days. Analysis of smears of epididymis and semi-thin sections of testes revealed that the more suitable specimens for the ultrastructural analysis were tissues of mice killed at the third week, following EMS administration. At this time, the spermatid was the damaged cell type. Abnormalities were mainly observed in the morphology of the nucleus, the acrosome, chromatin distribution and in the arrangement of the cytoplasmic microtubules, and binucleated spermatids were also observed. EMS has the capacity to penetrate the blood–testis barrier, and thus it can damage post-meiotic spermatogenic cells. However, morphological abnormalities could be the consequence of damage exerted on the differentiated spermatogonia stage, the most sensitive spermatogenic cell to the action of chemical agents or drugs. Our findings contribute to elucidate the action mechanism of the damage exerted by EMS administration on the germinal male cells. [ABSTRACT FROM AUTHOR]

Sexual dysfunctions have found an increasing attention in recent epidemiological studies of the ageing male. The purpose of this paper is to review the prevalence of sexual dysfunctions and risk factors based on community samples. Studies have not only demonstrated a strong age-related incline of erectile dysfunction (ED), but also of ejaculatory and orgasmic disorders (particularly a reduced or absent ejaculation). Despite a declining sexual desire, sexual interest remains present in old age. Lower urinary tract symptoms have been identified as strong risk factors for ED along with cardiovascular, metabolic, psychiatric disorders and lifestyle factors. The wide range of prevalence rate estimates is likely because of different definitions and criteria of sexual dysfunctions. More research is needed on other dysfunctions besides ED and on the partner relationship as a major determinant of sexual activity and satisfaction. The interrelationship between risk factors calls for interdisciplinary prevention and treatment approaches. As disability-free life expectancy keeps increasing, the need to identify, adequately assess and treat male sexual dysfunction as an important impediment to quality of life most likely will become even more pressing. [ABSTRACT FROM AUTHOR]

Presents abstracts of research papers discussed in the Tenth Andrology Symposium which was held on November 6, 2004 in Giessen, Germany. "Possibility of assisted reproduction in Klinefelter patients," by M. Bals-Pratsch, et al; "Treating varicocele: a futile exercise? Reassessing the Evers' meta-analysis," by F. Comhaire; "Infections, inflammation and male infertility," by T. Diemer and W. Weidner.

Intracytoplasmic sperm injection (ICSI) is an integral part of assisted reproduction. Although many papers have shown that global sperm count, sperm motility and sperm morphology of the ejaculate play no role in the fertilization rate after ICSI, embryologists who carry out ICSI, try to use the‘best looking’ spermatozoa. The aim of the study was to investigate whether those spermatozoa with the best morphology really achieve the highest fertilization rate. In the present study, a total of 798 spermatozoa used for ICSI were documented by high-resolution photo. After ICSI the oocytes were cultured in single droplets and the formation of pronuclei was assessed 16 h later. The spermatozoa (all normal according to WHO criteria) were classified into four groups of different morphology. Group 1: normal head shape (approximately 5 μm diameter), group 2: like group 1, but with 15–20% smaller diameter, group 3: like group 1, but with 15–20% larger diameter, and group 4: like group 1, but with slight mid-piece cytoplasmic irregularities. Using the Pearson chi-square test, no significant difference in terms of fertilization was found among the different groups, showing that marginal sperm differences do not alter the fertilization process in ICSI. [ABSTRACT FROM AUTHOR]

Gynaecomastia, the enlargement of the male breast, is considered as an andrological disease. To date, a review on male breast cancer (MBC) has not been published in an andrological journal. The papers underlying this review were published from authors of different institutions: Clinical Genetics, Dermatology, Gynaecology, Internal Medicine, Oncology, Pathology, Psychiatry, Radiology and Surgery. MBC accounts for approximately 1% of breast cancer patients. A total of 182 men died of breast cancer in 1999, in Germany. In the US, 1500 new cases per year occur. MBC accounts for<5% of surgically removed breast lumps. Diseases with increased oestrogen action increase the risk of MBC. Mutations of distinct genes are estimated to account for up to roughly 10% of MBC. BRCA1 and BRCA2 gene mutations are responsible for approximately 80% of the families with hereditary breast cancer. The diagnosis of MBC is not possible without histological examination. Different diagnostic procedures such as clinical diagnosis, sonography, mammography, fine-needle biopsy and core needle facilitate the decision whether a biopsy is necessary. [ABSTRACT FROM AUTHOR]

Summary. The role of Chlamydia trachomatis in the cause of male infertility is under discussion. This paper attempts to summarize data from the literature, which support the role of C. trachomatis in male infertility or oppose this suggestion. The following observations are based on a survey of the literature: 1 Chlamydia trachomatis is a frequent pathogen in male genital inflammation, the micro-organisms are rarely present in healthy men. 2 Without doubt, C. trachomatis causes inflammations of the male urethra and the epididymis. Prostatitis and glandulitis vesicalis are discussed controversially. 3 Chlamydia trachomatis antigen or DNA is not demonstrable in secretions of the male accessory glands including the semen with sufficient reproducibility. However, it is easily demonstrable in urethral swabs and the urine. 4 Determination of chlamydial antibodies in serum or semen does not conclusively indicate a current infection with C. trachomatis . 5 There are no conclusive studies showing that men infected with C. trachomatis are less fertile than uninfected men. 6 The male genital chlamydial infection is a threat to the female genital organs, because C. trachomatis infection of the female genital organs may be deleterious to female fertility. [ABSTRACT FROM AUTHOR]

Summary. Inflammatory disease is known to affect male reproductive function and fertility. Male accessory gland infections (MAGI) account for almost 15% of all cases of male infertility seen in infertility clinics. Infections of the male accessory glands are associated with increased counts of white blood cells in semen and elevated levels of pro-inflammatory cytokines in the semen and the testis. Numerous studies have underscored the importance of cytokines in the regulation of testicular and glandular function during pathophysiological events as well as under normal physiological conditions when cytokines act as growth and differentiation factors. The purpose of this paper is to particularly review the role of cytokines in the regulation of Leydig cell function in the testis primarily under pathophysiological conditions, and also considers clinical investigations that help to improve the evaluation and treatment of male infertility. [ABSTRACT FROM AUTHOR]

Summary. This paper reviews the latest data on chromosomal abnormalities in human gametes and embryos. A close relationship between such anomalies and reproduction failure in humans has been postulated, thereby underscoring the importance of ongoing studies into the mechanisms leading to anomalies. Until recently, knowledge of chromosomal anomalies in human gametes and embryos has been limited. Newly developed strategies (in vitro fertilization combined with micromanipulation techniques followed by multicolour fluorescence in situ hybridization, and PCR analyses) allow precise investigation of this problem. This review of the available information on the etiology of chromosomal anomalies indicates that some of the genetic anomalies in human gametes and early embryos result in reproductive failure. [ABSTRACT FROM AUTHOR]

Summary. Aquaporin (AQP) is a molecule that facilitates water permeability through cell membranes and is widely distributed in the mammalian body. Among members of the AQP family, AQP7 and AQP8 are predominantly expressed in the testis. This paper examined the expression of these two AQPs in the developing rat testis, using northern blot and immunohistochemistry to visualize their roles during the progression of spermatogenesis in the developing testis. In adult rats, expression of AQP7 was localized to spermatids, whereas AQP8 protein was observed in spermatocytes. In the developing testis, transcripts of AQP7 became detectable between 23 and 25 days post-partum, when round spermatids have been reported to appear. On the other hand, AQP8 mRNA was first detected between 13 and 16 days post-partum, consistent with the reported first appearance of spermatocytes (13–14 days). AQP7 and AQP8 proteins were detectable at 28 days post-partum. The results suggest that AQP7 and AQP8 appear in the testis in accordance with the maturation of germ cells, and are involved in spermatogenesis. [ABSTRACT FROM AUTHOR]

Summary. Prolonged incubation of human spermatozoa can have deleterious effects on sperm function. The aim of this paper was to describe the effects of a prolonged in vitro incubation, under similar conditions to those employed in human assisted reproduction, on various sperm functional parameters, and to investigate the effect of an antioxidant (catalase) on this system. Freshly collected ejaculates from 20 healthy donors were studied. Samples were divided into two aliquots: the first was incubated with Ham's F10 containing 3.5% HAS, and the second was incubated in the same medium plus catalase (100 units ml-1). All experiments were carried out with spermatozoa isolated using the swim-up technique. Spermatozoa recovered from the supernatant after 1 h (T1) of incubation in 5% CO2 in air at 37 °C, and after 5 h (T6), 23 h (T24) and 47 h (T48), were evaluated for concentration, motion parameters including hyperactivation (computer-assisted analysis), viability, ATP concentration, reactive oxygen species (ROS) generation, DNA integrity (acridine orange), and acrosome reaction (AR). The major alteration observed in sperm function during the prolonged in vitro incubation was a reduction in the number of motile spermatozoa, together with an impairment in the quality of sperm movement. ROS levels increased with the incubation time. No substantial modifications of sperm viability, chromatin condensation and AR inducibility were observed. The addition of catalase to the medium, while keeping ROS values within baseline levels, did not prevent the loss of motility or the corresponding increase in ATP. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the linkage of the association of azoospermia phenotype with genetic alterations, involved in genome instability. Male infertility is a multifactorial pathology, and genetic alterations might be the underlying factors in majority of cases of severe male infertility. The recent emergence of next-generation sequencing offers an opportunity to analyze many genes and their interactions at once, and whole-exome sequencing (WES) together with whole-genome sequencing (WGS) was recently suggested for implementation of diagnosis workup in severe infertility cases. However, the reports on WES in conjunction with burden tests and gene network analysis are scarce or lacking in cases of severe male infertility. WES was performed on 21 nonobstructive azoospermia patients. DNA samples were sequenced using the Twist Comprehensive Exome Panel. Genetic burden test was performed with Testing Rare vAriants using Public Data. Protein interactions were investigated with ConsensusPathDB and Cytoscape. For single nucleotide variants and copy number variations (CNV) analysis, samples were analyzed with the Illumina's BaseSpace Variant Interpreter. Genetic variant burden was found elevated in 1,473 genes out of 30,000 known testis expressed genes. Three hundred and two genes with increased loss-of-function (LoF) variant set were present in more than one sample. Overrepresentation analysis with pathway-based set of genes with high variant burden demonstrated 26 pathways. Overrepresentation analysis with protein complex-based gene sets obtained 14 sets, showing the involvement in cell proliferation and DNA repair. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) network analysis with Cytoscape identified two clusters: (1) genes, involved in DNA binding/condensation and repair processes and (2) genes with the role in ribosome biosynthesis and gene expression processes. Increased loss of function germline variant burden and sumoylation may have critical significance in spermatogenesis. These parameters may be used for focused diagnosis in nonobstructive azoospermia patients. This may have both general significance for the decreased organism functionality but in particular is critical in spermatogenesis. [ABSTRACT FROM AUTHOR]

Objective. The probable relationship between serum vitamin D levels and male fertility is being increasingly investigated; however, the findings have been controversial. This review dealt with assessing the relationship between serum vitamin D levels and male fertility and sperm quality by executing systematic review and meta-analysis of the published data. Methods. The meta-analysis was executed as per the PRISMA 2020 statement. The protocol was registered with PROSPERO (CRD42022327583). Relevant literature was retrieved by searching online databases, including Embase, Scopus, PubMed, Web of Science, and the Cochrane Library, up to December 1st, 2022. Additionally, Google Scholar was searched to assess relevant articles. To ensure a more comprehensive review, unpublished articles, gray literature, and references of suitable articles were also assessed to find additional eligible publications. The articles that satisfied the inclusion criteria were evaluated for their quality using the Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted through STATA 12. Results. Twenty-four articles, comprising 7,345 participants in total, were chosen for the systematic review and meta-analysis. The resulting data indicated that serum vitamin D levels infertile males were remarkably elevated compared with that in infertile males (weighted mean difference (WMD) = 7.06, 95% confidence interval (95% CI) = 2.51–11.62, P = 0.002), and its deficiency (<20 ng/mL or 50 nmol/L) significantly reduced sperm concentration (WMD = 8.54, 95% CI = 4.01–13.06, P < 0.001), total sperm count (WMD = 14.43, 95% CI = 1.30–27.55, P = 0.031), sperm motility (WMD = 6.40, 95% CI = 3.15–9.64, P < 0.001), sperm progressive motility (WMD = 5.00, 95% CI 1.09–8.92, P = 0.012), and altered sperm morphology (WMD = 0.74, 95% CI = 0.20–1.27, P = 0.007). The data analysis determined that vitamin D did not remarkably influence sperm volume (WMD = 0.17; 95% CI = −0.00–0.34; P = 0.050). Conclusion. The acquired data implied that serum vitamin D is significantly associated with male fertility and sperm quality. This finding holds crucial implications for patients suffering from male infertility. [ABSTRACT FROM AUTHOR]

Calcium ion enters the sperm through a specific calcium channel, CatSper. This voltage-sensitive channel is stimulated by intracellular alkalization and progesterone. This study is aimed at investigating the effects of CatSper inhibition or stimulation on sperm motility, viability, and sperm function regulators such as mitochondrial membrane potential (MMP), ATP, and reactive oxygen species (ROS) production. This study was performed on 30 semen samples of fertile volunteers, referred to Shiraz Fertility Center. The semen samples were diluted to 20 × 10 6 sperm/mL. The samples were divided randomly into control, solvent, progesterone (10 μM), NNC (2 μM), and NNC+progesterone groups. Sperm kinematics, viability, MMP, ATP content, and the amount of ROS production were assessed using VT-SPERM3.1, eosin staining, JC1 flow cytometry, bioluminescence, and chemiluminescence methods, respectively. Sperm viability and total and progressive motility were significantly decreased in the NNC and NNC+progesterone groups. The amplitude of lateral head displacement (ALH) and curvilinear velocity (VCL) was reduced in the NNC-containing groups. These parameters did not change in the progesterone group. ROS production by viable spermatozoa in the NNC and NNC+progesterone groups was significantly higher than the controls. MMP and ATP content did not show any significant difference with controls in none of the experimental groups. NNC inhibits the CatSper and reduces human sperm motility and viability. These harmful NNC effects were not due to their impact on MMP or ATP production but are likely because of intracellular calcium reduction and higher ROS production. Progesterone at 10 μM concentration had no significant effect and may not be a considerable stimulator for CatSper. [ABSTRACT FROM AUTHOR]

As a chemotherapeutic drug, cyclophosphamide (CP) has a negative impact on male fertility due to its reproductive toxicity. Melatonin (Mel) promotes the male reproductive system and increases testosterone synthesis. This study is aimed at exploring the molecular mechanism of Mel as a protector of male fertility against CP-induced cytotoxicity. A CP toxicity model was established in adult ICR male mice by intraperitoneal injection of 100 mg/kg CP every other day for a week. Protective effects of Mel on the testis from CP-induced damage were evaluated using four groups of ICR male mice that received intraperitoneal injections of normal saline, 100 mg/kg CP, 10 mg/kg Mel, or the same dosage of CP and Mel, respectively. Testis morphology was observed by hematoxylin and eosin (HE) staining. Sperm quality parameters were evaluated, and sperm function was studied by in vitro fertilization (IVF). Proliferation, meiosis, and pyroptosis markers were examined by western blot. Results showed that CP treatment induced testis toxicity in a time-dependent manner with the most severe damage to the testis at two weeks post CP treatment. CP-treated mice showed reduced testicular weight and impaired spermatogenesis by downregulating PCNA and SYCP3, reduced serum testosterone levels, decreased sperm counts and motility, increased seminiferous tubule vacuolization, and oxidative damage to spermatogenic cells. All these effects, apart from testicular weight, could be ameliorated by Mel administration. The IVF experiment revealed that CP treatment reduced the rates of sperm fertilization and blastocyst development, which were also enhanced by Mel. Mel-treated mice also showed increased expression of proliferation-associated protein PCNA and meiosis-associated proteins REC8, STRA8, and SYCP3, which were all reduced by CP. Furthermore, Mel inhibited the pyroptosis of spermatogenic cells by reducing GSDMD and IL18 expression. In conclusion, this study indicated that Mel might protect the testis from CP-induced DNA damage to germ cells through the alleviation of pyroptosis. [ABSTRACT FROM AUTHOR]

Background. Aromatase inhibitors (AIs) can significantly improve semen parameters in infertile men. In this study, we investigated the efficacy of AIs for azoospermia in a Chinese population with AZFc microdeletion. Aims. Patients with AZFc microdeletion who were treated with AIs were analyzed retrospectively by collecting clinical data, including their hormone profile and treatment outcome. Patients were divided into those with sperm in their semen after AI treatment (group A) and those without sperm in their semen after AI treatment (group B). Results. The rate of Y chromosome AZF microdeletions was 9.30% (313/3364) from March 2015 to March 2021, among which patients with complete AZFc microdeletion accounted for 63.2% (198/313), and of the 198 patients with AZFc microdeletion, 69.7% (138/198) showed azoospermia. Forty-six (33.3%) of the azoospermic patients had sperm in their semen after AI administration. Testosterone (T) and testosterone-to-estradiol ratio (T/E2) levels were higher in group A than those in group B after treatment, and the differences were significant (T, P = 0.038 ; T/E2, P = 0.004). Paired t -test demonstrated that the change of T levels before and after treatment was statistically significant (P = 0.003). The increased E2 and T/E2 ratio levels before and after treatment were not statistically significant (P = 0.057 and 0.080), but they were close to the threshold value (P = 0.05). Conclusions. Patients with AZFc microdeletion accounted for the largest proportion of male infertility caused by Y chromosome microdeletions. AIs can promote spermatogenesis in azoospermic patients with AZFc microdeletion, and sperm could be found in the semen of some patients after AI administration. T and T/E2 levels after AI treatment could be used as biomarkers to distinguish azoospermic patients with AZFc microdeletion who responded better to AIs from those who did not respond well. [ABSTRACT FROM AUTHOR]

Introduction. The etiology of male infertility characterized by non-obstructive azoospermia is largely unknown, especially at the molecular level. Identifying dysregulated microRNAs (miRNAs) in male infertility would be useful to achieve a more profound understanding of its pathogenesis. Methods. Small RNA sequencing was performed on the testicular tissues of 10 nonobstructive azoospermic patients with the Sertoli cell only syndrome (SCOS) and 8 obstructive azoospermic individuals with normal spermatogenesis. The expressions of two dysregulated miRNAs were validated by quantitative real-time polymerase chain reaction, confirming the results obtained by sequencing analysis. Bioinformatic analysis was undertaken to identify the main pathways impaired in complete spermatogenic failure. Results. A total of 136 miRNAs were detected to be differentially expressed in the Sertoli cell only syndrome group in comparison with the obstructive azoospermia group. Bioinformatic analysis suggested that the altered miRNAs were substantially involved in pathways related to spermatogenesis. Conclusions. Our study investigates the entire profile of miRNAs with emphasis on the crucial role of miRNAs in idiopathic Sertoli cell only syndrome, suggesting potential targets for employing molecular therapeutic strategies in the treatment of spermatogenic failure. [ABSTRACT FROM AUTHOR]