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"Male reproduction"
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Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation
Varicocele has been associated with reduced male reproductive potential. With the advances in biomolecular techniques, it has been possible to better understand the mechanisms involved in testicular damage provoked by varicocele. Current evidence suggests the central role of reactive oxygen species （ROS） and the resultant oxidative stress （OS） in the pathogenesis of varicocele-associated male subfertility although the mechanisms have not yet been fully described and it is likely to be multifactorial. Excessive ROS is associated with sperm DNA fragmentation, which may mediate the clinical manifestation of poor sperm function and fertilization outcome related to varicocele. Testing of ROS/OS and DNA fragmentation has the potential to provide additional diagnostic and prognostic information compared to conventional semen analysis and may guide therapeutic management strategies in individual patient.
Journal Article
The Relationship Between Sperm Midpiece Details and DNA Fragmentation in Human Sperm
Sperm DNA fragmentation is associated with poor sperm quality and reproductive outcomes. Free radicals are a significant cause of DNA fragmentation, with mitochondria being the primary intrinsic source. To investigate the relationship between midpiece measurements containing mitochondria and sperm DNA fragmentation, and to determine the ideal midpiece area. Demographic data, semen analysis results, and DNA fragmentation values were prospectively collected from 239 men with infertility complaints. Detailed analyses and morphometric measurements were performed on 50 spermatozoa from each patient, totaling 11,950 spermatozoa. The ideal DNA fragmentation index (DFI) cutoff value was calculated. Patients were classified into three subgroups based on midpiece length, midpiece width, and midpiece area measurements. The correlation between mid-piece measurements and DFI was investigated. The cutoff value for DFI was determined as 19.50. The odds ratio evaluating the relationship between morphology status and high DFI was 0.159 (95% CI: 0.089—0.282). It was observed that midpiece length and width have statistically significant but low correlations with DFI, whereas midpiece area shows a higher correlation. Finally, based on DFI values, the ideal midpiece area was between 2.31 and 3.13 µm
2
. There is a significant correlation between sperm midpiece area and DFI value, surpassing that of length and width. Future studies may yield important insights by exploring the impact of midpiece area measurements on reproductive outcomes.
Journal Article
1-DNJ Alleviates Obesity-Induced Testicular Inflammation in Mice Model by Inhibiting IKKβ/ NF-kB Pathway
Obesity is associated with chronic inflammation that affects various organs in the body, including the reproductive system, which is a key factor in male infertility. 1-Deoxynojirimycin (1-DNJ) is a natural alkaloid in mulberry leaves, which has anti-inflammatory capabilities, yet, it’s effects on obesity-induced inflammation-related male infertility remain unclear. Therefore, this research investigates the underlying mechanism by which 1-DNJ may mitigate fertility impairment in male mice caused by obesity-related inflammation. Male mice with high-fat diet (HFD)-induced obesity were treated with 1-DNJ or metformin for 8 weeks. Metabolic profiles were evaluated by enzyme method. Reproductive capacity was assessed by sperm viability, motility and counts, immunohistochemistry was performed to evaluate the testicular damage caused by obesity and inflammation. The inflammation was assessed by measuring the levels of tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and interleukin 6 (IL-6). The activation of IκB kinase β (IKKβ) and nuclear factor κB (NF-κB) was examined using western blot and immunohistochemistry. HFD induced obesity in mice with obvious lipid metabolism disorder. The obese male mice had a decreased testosterone level, impaired sperm motility, and increased inflammatory factors. 1-DNJ treatment improved the testosterone level in the obese mice, ameliorated the testicular structure damage and improve sperm viability. In addition, 1-DNJ treatment inhibited IKKβ/NF-kB signaling pathway and reduced inflammation in obese mice. 1-DNJ can improve the fertility of obese men by reducing obesity as well as obesity-induced inflammation. These findings provide new insights for 1-DNJ to alleviate inflammation caused by obesity and provide future possibilities for treating male infertility.
Journal Article
Changes in Sperm Parameters with Time in Men with Normal and Abnormal Baseline Semen Analysis
The association between paternal age and sperm quality in the population level has been previously studied. Only limited data exists regarding the intra-personal variations in semen parameters among fertile and infertile men over time. We aimed to assess trends over time in semen parameters among men with normal and abnormal baseline sperm parameters and investigate potential risk factors for sperm quality deterioration. This retrospective cohort study was conducted at a university-affiliated medical center in vitro fertilization (IVF) unit. Patients with at least two semen analyses (SA) performed > 1 year apart, with the last SA done between 2017 and 2021, were included. The study consisted of two main analyses—comparison of intra-patient’s sperm parameters changes in men with normal and abnormal baseline SA (BSA) and analysis of risk factors for developing abnormal semen parameters over time in men who had normal BSA parameters. This study included a total of 902 men assessed for infertility with normal and abnormal BSA. The average time interval between tests was 1015 days (range 366–7709 days). Among individuals with normal BSA, there was a mild decline in most parameters—concentration (− 6.53 M/ml), motility (− 7.74%), and total motile count (TMC) (− 21.80 M) (
p
< 0.05 for all parameters). In contrast, a slight improvement in most parameters, except for concentration, was noted in men with abnormal BSA—volume (+ 0.21 ml), motility (+ 8.72%), and TMC (+ 14.38 M) (
p
< 0.05 for all parameters). Focusing on men with normal BSA, 33.5% of individuals developed abnormality in one or more of their sperm parameters over time, within a mean time of 1013 ± 661 days. We also found that only time between tests emerged as an independent prognostic factor for the development of abnormal SA later. Interestingly, sperm deterioration in participants in their third, fourth, and fifth decades of life with normal initial semen analysis was similar. Our study provides evidence of a decline in semen quality over time in individuals with normal BSA, in contrast to men with abnormal BSA. Longer time intervals between tests independently increase the risk of sperm abnormalities.
Journal Article
Determination of M1/M2 Macrophage Polarization in Ipsilateral and Contralateral Rat Testis Tissue Following Unilateral Torsion/Detorsion
The present study investigates the changes in M1/M2 macrophage polarization resulting from unilateral testicular torsion in the bilateral testis. The study sample included 63 male Sprague–Dawley rats, which were randomly divided into nine groups (n = 7): Control, Sham (4 h (4 h), 24 h, 7 days (7d), 14d), and Torsion/Detorsion (T/D) (4 h, 24 h, 7d, 14d). Histopathological evaluations revealed no changes in the Sham groups, while T/D was noted to cause edema, vascular occlusion, disruption of seminiferous tubule epithelial organization, germ cell abnormalities and structural anomalies in the experimental rats, the severity and extent of which increased from 4 h to 14d after T/D. The Cosentino scores used to determine the degree of histological damage were consistent with the histopathological findings in all groups, while the Johnsen scores, as a marker of spermatogenesis, were lower in the T/D groups. Seminiferous tubule diameters and germinal epithelial thickness decreased significantly in parallel with increased tubule damage in the ipsilateral testicles. Testicular torsion significantly affected sperm motility, with significant reductions observed in the T/D 7d and T/D 14d groups. A hormone profile analysis revealed decreased testosterone levels in both the Sham and T/D groups when compared to the Controls. CD68 and CD163 immunoreactivities, as M1 and M2 macrophage surface markers, were determined in the testicular tissue using the avidin–biotin-peroxidase complex method. T/D interventions caused M1/M2 macrophage polarization changes and increased M1 macrophages, particularly in contralateral testicular tissue. The increase in M1 macrophages in contralateral testicular tissue following T/D in the present study suggests that cell processes, including macrophages, may play an important role in contralateral testicular injury.
Journal Article
The Effect of Thymoquinone on the TNF-α/OTULIN/NF-κB Axis Against Cisplatin-İnduced Testicular Tissue Damage
One of the adverse effects of the antineoplastic drug cisplatin (CS) is damage to testicular tissue. This study aimed to examine the potential therapeutic effect of thymoquinone (TQ), a strong antioxidant, against testicular damage caused by CS. In the experiment, 28 rats were used, and the rats were randomly divided into four groups: control (
n
= 7), CS (
n
= 7), CS + TQ (
n
= 7), and TQ (
n
= 7). The experiment was called off after all treatments were finished on day 15. Blood serum and testicular tissues were utilized for biochemical, histological, immunohistochemical, mRNA expression, and gene protein investigations. The testosterone level decreased and oxidative stress, histopathological damage, dysregulation in mitochondrial dynamics, inflammation and apoptotic cells increased in testicular tissue due to CS administration. TQ supplementation showed anti-inflammatory, antioxidant, and anti-apoptotic effects in response to CS-induced testicular damage. In addition, TQ contributed to the reduction of CS-induced toxic effects by regulating the TNF-α/OTULIN/NF-κB pathway. TQ supplementation may be a potential therapeutic strategy against CS-induced testicular damage by regulating the TNF-α/OTULIN/NF-κB axis, inhibiting inflammation, oxidative stress, and apoptosis.
Journal Article
Role of Estrogen Signaling in Notch Pathway Activation in Sertoli Cells
Sertoli cells constitute a somatic component of seminiferous epithelium in mammalian testis which supports the process of spermatogenesis. These cells are sensitive not only to the male sex hormones androgens, but also to their metabolites, estrogens. In this study, we aimed to explore the action of estrogen signaling in rodent Sertoli cells on the activity of canonical Notch pathway, which provides contact-dependent communication between the cells of seminiferous epithelium. Experiments performed on Sertoli cell line and primary Sertoli cell cultures demonstrated that 17β-estradiol, acting through estrogen receptor 2, enhances Notch1 activation, transcriptional activity of recombination signal binding protein for immunoglobulin kappa J region (RBPJ), interaction of RBPJ with
Hes1
promoter, and the expression of the
Hes1
effector gene and protein. On the other hand, 17β-estradiol by binding to estrogen receptor 1 reduces the expression of the
Hey1
effector gene. In contrast to nuclear estrogen receptors, no evident role of G protein-coupled estrogen receptor 1 in regulating Notch1 signaling activity in Sertoli cells has been found. The data presented indicate the role of nuclear estrogen receptor signaling in the control of Notch1 pathway activity in Sertoli cells, and thus reveal new mechanism of estrogen action in maintaining homeostasis of the seminiferous epithelium.
Journal Article
Persistent organic pollutants and male reproductive health
Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.
Journal Article