Risk Factor For Male Infertility Research Articles

Preventable Male Infertility: Identifying the Modifiable Risk Factors

Background: Infertility is a global health issue, with both genders having equal contribution. Approximately 15% of couples having difficulty to conceive after one year of consistent, unprotected sexual activity, infertility. Objectives: To identify the modifiable risk factors of male infertility in patients visiting a private hospital of Peshawar.Material and Methods: The study was a descriptive Cross-sectional of six months duration. A total sample size of 733 married male patients visiting private hospital were included and those who were reluctant to participate were excluded. Structured questionnaire were filled. Non probability convenience sampling technique was used and data was analyzed using SPSSversion 22Results: Out of 733 sample size 397(54%),336 (45.9%) had secondary and primary infertility, respectively. Risk factors, like obesity, smoking, diabetes mellitus, congenital anomalies and varicocele were linked to infertility with p valve < 0.05. The majority 568 (77.5%) had normal semen count, Oligospermia and Azoospermia were 11%.Conclusion: Our study concluded that smoking, diabetes mellitus, obesity, semen abnormalities and congenital anomalies were related to both primary and secondary infertility among men in Peshawar.Keywords: Male infertility, Obesity, Risk factors, Semen analysis, Semen abnormalities, Tobacco use.

Machine learning approach to assess the association between anthropometric, metabolic, and nutritional status and semen parameters.

Many lifestyle factors, such as nutritional imbalance leading to obesity, metabolic disorders, and nutritional deficiency, have been identified as potential risk factors for male infertility. The aim of this study was to evaluate the relationship between semen parameters and anthropometric, metabolic and nutritional parameters. Relationship was first assessed individually, then after the application of a previously constructed and validated machine learning score that allows their combination. Anthropometric, metabolic, antioxidant, micronutrient, and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France (Jean-Verdier ART Center Hospital, Bondy; North Hospital ART Center, Saint-Étienne; Navarre Polyclinic ART Center, Pau; and Cochin Hospital ART Center, Paris) between September 2009 and December 2013 were collected. After assessing standard correlation analysis, a previously built machine learning model, providing a score ranging from 0 (the poorest) to 1 (the most favorable), was calculated for each man in the study cohort. This machine learning model, which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature, provides a more holistic evaluation of the influence of the considered markers (anthropometric, metabolic, and oxidative status). We observed a significant correlation of some anthropometric, metabolic, and nutritional disorders with some sperm characteristics. Moreover, an unfavorable machine learning score was associated with a high level of sperm DNA fragmentation. Favorable anthropometric, metabolic, and oxidative patterns, which may reflect an appropriate lifestyle, appear to positively impact overall health, in particular reproductive function. This study, consistent with previous publications, suggests that beyond semen quality parameters, in an essential assessment of male fertility, other key factors should be taken into account. In this regard, the application of emerging artificial intelligence techniques may provide a unique opportunity to integrate all these parameters and deliver personalized care.

Decreased AdipoR1 signaling and its implications for obesity-induced male infertility

Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced male subfertility have been reported, the entire mechanism of obesity-induced male infertility still remains unclear. Here, we show that sperm count, sperm motility and sperm fertilizing ability were decreased in male mice fed a high-fat diet and that the expression of the AdipoR1 gene and protein was decreased, and the expression of pro-apoptotic genes and protein increased, in the testis from mice fed a high-fat diet. Moreover, we demonstrate that testes weight, sperm count, sperm motility and sperm fertilizing ability were significantly decreased in AdipoR1 knockout mice compared to those in wild-type mice; furthermore, the phosphorylation of AMPK was decreased, and the expression of pro-apoptotic genes and proteins, caspase-6 activity and pathologically apoptotic seminiferous tubules were increased, in the testis from AdipoR1 knockout mice. Furthermore, study findings show that orally administrated AdipoRon decreased caspase-6 activity and apoptotic seminiferous tubules in the testis, thus ameliorating sperm motility in male mice fed a high-fat diet. This was the first study to demonstrate that decreased AdipoR1/AMPK signaling led to increased caspase-6 activity/increased apoptosis in the testis thus likely accounting for male infertility.

Observational Cross-Sectional Study on Mediterranean Diet and Sperm Parameters

Infertility, affecting 15 to 25% of couples in the most developed countries, is recognized by the World Health Organization as a public health issue at a global level. Different causes are acknowledged to reduce fertility in both sexes. In particular, about 40–50% of cases recognize a male factor. Dietary habits and lifestyle are acknowledged to influence sperm quality and are therefore important modifiable factors in male reproductive health. Conditions such as overweight/obesity, impaired glucose metabolism and determinants of metabolic syndrome, together with unhealthy lifestyle behavior, i.e., smoking cigarettes and physical inactivity, are suggested to have a negative impact on male fertility. While individual elements and characteristics of the Western diet and habits are considered risk factors for male infertility, the Mediterranean diet (MD) seems to promote reproductive potential for improving sperm quality. It is also interesting to note that previous observational studies reported a positive correlation between the consumption of the single food classes of the MD pattern (i.e., vegetables and fruits, poultry, fish and seafood, whole grains, low-fat dairy products) and the quality of several sperm parameters. To evaluate the relationship between sperm parameters and MD adherence, we performed a cross-sectional study on the seminal data of 300 males (mean age 34.6 ± 9.1 years) who spontaneously referred to our center of reproductive medicine. The evaluation of adherence to MD was performed with a validated 14-point Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Our findings showed that sperm parameters such as sperm count, motility, viability and normal morphology are significantly and positively correlated with MEDAS, independently of BMI and age. In addition, the application of an ROC curve on MEDAS value vs. seminal alterations identified 6.25 as the score threshold value below which altered sperm parameters were more likely to occur [AUC = 0.096 (CI: 0.059–0.133; p < 0.00)]. Therefore, adhering to the MD with at least a MEDAS score of 6.26 increases the probability of normozoospermia. Moreover, subjects who had a MEDAS value lower than 6.25 had an Odds Ratio of 6.28 (CI = 3.967–9.945) for having at least one altered sperm parameter compared to those who were more adherent to the MD. In conclusion, our findings show that a higher adherence to the MD is associated with better semen parameters, in particular in relation to sperm count, sperm concentration, typical sperm morphology, and sperm progressive motility.

Investigation of the Relationship between HIWI3 rs11703684 (C>T) Polymorphism and Idiopathic Azoospermia/Oligozoospermia in the Kurdish Population of Kermanshah

Background & Objective: Genetic factors play a major role in the development of male idiopathic infertility. Because of the multi-genetic base of this disease, not all genetic factors have been investigated. PIWI genes have been reported to be involved in the regulation of piRNAs in spermatogenesis. Our study assessed the association between HIWI3 rs11703684 (C>T) gene polymorphism with the risk of male idiopathic azoospermia/oligozoospermia in the Kurdish population of Kermanshah.
 Materials & Methods: In this case-control investigation, we included two hundred individuals consisting of 100 men with idiopathic azoospermia/oligozoospermia and 100 fertile men as the control group. To determine genotypes of HIWI3 C>T polymorphism, we used the Tetra Arms-PCR technique and significant values were considered as p<0.05.
 Results: Our findings did not show a statistically significant difference in the genotype frequency of the recessive model (P = 0.118; OR = 0.158; CI, 0.019–1.339), dominant (P = 0.169; OR = 0.625; CI, 0.341–1.144) and co-dominant (P = 0.527; OR = 0.778; CI, 0.417–1.450). In addition, the results described a negative difference in allelic frequency of HIWI3 (rs11703684 C>T) in men with idiopathic azoospermia/oligozoospermia and control group (P = 0.288; OR = 0.749; CI, 0.463–1.212).
 Conclusion: The current study does not indicate the probability effect of HIWI3 rs11703684 (C>T) gene polymorphism on the male idiopathic azoospermia/oligozoospermia in the Kurdish population of Kermanshah. The critical role of PIWI genes in spermatogenesis and as a candidate risk factor for male infertility remained unknown.

Garcinia Mangostana Pericarp Extract Protection on Reproductive Function of Obese-Diabetic Rats Model

Background: Type 2 diabetes mellitus (T2DM) in obese has been considered a risk factor for male infertility. Garcinia mangostana pericarp extract (GMPE) is known to have anti-hyperglycemic, anti-diabetic, and anti-inflammatory effects.  This study aimed to evaluate the effect of GMPE therapy on reproductive function in obese T2DM rats by examining testosterone level, testicular histopathological features, and hs-CRP level.Methods: Thirty-six male Wistar rats, aged 2-3 months, were randomly divided into 6 groups and treated with a standard diet (NC), high-fat diet (HFD) with GMPE 200 mg/kgBW (obese GMPE control/OGC200), HFD with 45 mg/kgBW STZ-NA (obese-diabetic control/ODC), obese-diabetic rats with GMPE 100 (DG100); 200 (DG200); and 400 mg/kgBW (DG400). STZ-NA was administered after 8 weeks of HFD treatment and followed by GMPE for 8 weeks after T2DM was confirmed. The level of hs-CRP and testosterone were measured in the serum using an enzyme-linked immunosorbent assay. Testicular histopathological examination was measured after 8 weeks of treatment by using Modified Jonhson Score (MJS) with HE staining.Results: ODC rats significantly showed increased hs-CRP level compared to NC (8.76±0.27 vs 0.30±0.07 ng/mL, P<0.001) and reduced testosterone level and MJS compared to NC (73.69±2.22 vs170.14±1.34 ng/dL, 4.57±0.93 vs 9.87±0.16 MJS, respectively, P<0.001). Testosterone and hs-CRP levels showed a negative and significant correlation (r=-0.974 and P<0.001). On the treatment group, GMPE significantly reduced hs-CRP and increased testosterone levels in a dose-dependent manner.Conclusion: GMPE effectively protects reproductive function in obese DM rats by increasing testosterone levels and advanced spermatogenesis, as well as decreasing hs-CRP level.

[Analysis of copy number variation in AZF region of Y chromosome in patients with spermatogenic failure].

To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.

Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice

Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.

Obesity May Impairs Mice Testicular Structure by STAT3/CYP19A1/Testosterone

Obesity is an increasing serious global public health issue and a risk factor for male infertility. Aromatase expression level is elevated in obese men, and this high level is as-sociated with diminished serum testosterone levels. We explored the underlying mechanism of infertility in obese men. Genome-wide association study datasets were used to predict the causal relationship between obesity and male infertility. An obese male mouse model was generated by feeding mice a high-fat diet while control model was generated by feeding mice a normal chow diet. Serum indicators including free fatty acids, insulin, Follicle-stimulating hormone, and testosterone were measured using ELISA, and impaired fertility in mice was demonstrated using immunohistochemistry. The expression levels of STAT3 and CYP19A1 were measured by RT-qPCR and western blotting, respectively. Simultaneous bioinformatics analysis of publicly available data was performed using the R programming language and JASPAR database. Obesity might lead to male infertility from a genomic perspective. Obese mice displayed reduced serum testosterone and follicle stimulating hormone levels along with structural abnormalities, ectopic lipid deposition, and chronic inflammation in the testes. Upregulation of STAT3/CYP19A1 expression in obese mice was linked to reduced serum testosterone levels and impaired fertility. Our observation may support the hypothesis that since the elevation of STAT3 expression in obesity, the promoted expressed CYP19A1 could increase a shift from testosterone to estrogens. The persistently elevated level of estrogen will further stimulate STAT3, which may constitute a positive feedback loop. These findings provide new insights into the mechanisms of obesity-mediated male fertility impairment.

Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.

Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility. We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval. 24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress. Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.

Variation of the genes encoding antioxidant enzymes SOD2 (rs4880), GPX1 (rs1050450), and CAT (rs1001179) and susceptibility to male infertility: a genetic association study and in silico analysis.

Enzymatic factors including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) are among the most important protective antioxidant systems in human semen. This study was conducted to investigate the association between the activities of the mentioned enzymes in semen and also the association between SOD2 rs4880, GPX1 rs1050450, and CAT rs1001179 polymorphisms with male infertility, which was followed by a bioinformatics approach. In a case-control study, 223 infertile men and 154 healthy fertile men were included in the study. After extracting genomic DNA from semen samples, the genotype of rs1001179, rs1050450, and rs4880 polymorphisms was determined using the PCR-RFLP. Next, the activities of SOD, CAT, and GPX enzymes were also measured in semen. Bioinformatics software was used to investigate the effect of polymorphisms on the function of genes. Data analysis indicated that rs1001179 polymorphisms were not associated with male infertility. But our data revealed that the rs1050450 polymorphism is associated with a reduced risk of male infertility as well as asthenozoospermia and teratozoospermia. In addition, rs4880 polymorphism was associated with an increased risk of male infertility as well as teratozoospermia. Further analysis showed that the activity of the CAT enzyme in the infertile group is significantly higher than in the fertile group, but the activity of GPX and SOD enzymes in the infertile group is significantly lower than in the fertile group. Bioinformatic analysis showed that rs1001179 polymorphism affects the transcription factors binding site upstream of the gene, while rs1050450 and rs4880 polymorphisms had an essential role in protein structure and function. On the other hand, rs1050450 (T allele) was exposed to a reduced risk of male infertility and may be a protective factor. And SOD2 rs4880 (C allele) is associated with an increased risk of male infertility, and it is considered a risk factor for male infertility. To reach accurate results, we recommend that the study of SOD2 rs4880 and GPX1 rs1050450 polymorphism effects in the different populations with a larger sample size and meta-analysis are needed.

A Scoping Review of Male infertility Risk factors and Potential Causes

Limited studies have been conducted on the probable causes and risk factors for male infertility, despite evidence of diminishing sperm counts globally and increasing male infertility rates. Because there are few primary treatments for male unproductiveness, knowing the reason and risk characteristics will help identify particular ways to prevent it. Detect gaps of possible risks and reasons affecting on male to enable further specialized innovation and research are summarized in this review article. The review covered research from scholarly/scientific journals that addressed male infertility “its causes and risk factors”. There was no time or place restriction. Particular life style such as (smoking, alcohol intake and medication, the high prevalence of obese men, environmental contamination due to indiscriminate use   especially (pesticides and heavy metals), electronic devices and male age are discussed. In addition, the genetics factors, STDs, varicocele, ROS and endocrine disorder and the influence on human spermatogenesis are considered. In our opinion, enhance comprehension   “the causes and risk factor” will make it easier to develop primary preventive and to guide therapy for male infertility.

O-046 Nutritional habits might improve your fertility

Abstract Many lifestyle factors have been identified as risk factors for male infertility. For example, an unbalanced diet leading to overweight, obesity, metabolic disorders, and micronutrient deficiencies can have consequences for male reproductive functions. Obese men present more often altered semen parameters and a reduced chance of pregnancy naturally or after medically assisted procreation. In some cases, weight loss can reverse the adverse effects of obesity. However, few interventional studies have demonstrated the effectiveness of a preconceptional intervention in men. In contrast, more and more studies are highlighting the importance of a balanced diet and physical activity to improve fertility. A qualitatively adequate and balanced diet and appropriate daily intake of micronutrients are fundamental for male reproductive functions. Some teams have highlighted the benefits of the Mediterranean diet on sperm production, whereas the Western diet, including reconstituted meats, fried foods, and sweet foods and drinks, was associated with altered semen parameters. However, few interventional studies have confirmed the impact of men's diets on the chances of natural or medically assisted pregnancy and live birth, and their results are controversial. Therefore, robust randomised controlled studies are needed. Practical advice and education can be recommended to men who wish to conceive to help them maintain or achieve the public health recommendations that encourage a balanced diet, such as the Mediterranean diet.

Does an increase in adipose tissue 'weight' affect male fertility? A systematic review and meta-analysis based on semen analysis performed using the WHO 2010 criteria.

Obesity negatively impact on the metabolism of sex hormones, leading to reduced testosterone serum levels. However, how the obesity could negatively impact on the overall gonadal function, particularly on male fertility, remained unclear so far. To systematically review evidences regarding the influence of body weight excess on the sperm production. A meta-analysis was conducted, searching all prospective and retrospective observational studies reporting male subjects older than 18 years old, with body weight excess from overweight to severe obesity were considered. Only studies using the V edition of the World Health Organization (WHO) manual for semen analysis interpretation were considered. No specific interventions were considered. Search was focused on studies comparing overweight/obese to normal weight subjects. Twenty-eight studies were considered. Total sperm count and sperm progressive motility were significantly lower in overweight compared to normal weight subjects. Meta-regression analyses demonstrated that patients' age impacted on sperm parameters. Similarly, obese men showed lower sperm concentration, total sperm number, progressive and total motilities, and normal morphology lower than normal weight subjects. Reduced sperm concentration in obese men was influenced by age, smoking habit, varicocele, and total testosterone serum levels at meta-regression analyses. The male potential fertility is reduced in subjects with increased body weight, compared to normal weight men. The higher was the increased body weight, the worst was the sperm quantity/quality. This result comprehensively included obesity among non-communicable risk factor for male infertility, shedding new lights on the negative impact of increased body weight on overall gonadal function.

Mediterranean Diet and Male Fertility

Diet has an impact on male reproductive potential, but few studies have focused on the specific impact of food groups or dietary patterns on fertility. Male reproductive health, as indicated by improved semen parameters and increased chances of conceiving, is associated with the Mediterranean diet, while the Western diet is considered a risk factor for male infertility. The potential mechanisms that may explain the impact of these diets on semen quality are still largely unknown. However, numerous studies suggest that nutritional interventions are crucial for the preservation and improvement of male fertility. This review aims to summarize the most recent evidence on the influence of components of the Mediterranean diet on sperm parameters. Unlike other risk factors, dietary modulation represents a great opportunity for improving overall health and can also be an important tool in recommendations for male reproductive health.

Association of MTR A2756G and MTRR A66G Polymorphisms With Male Infertility: An Updated Meta-Analysis.

The objective of the present study was to find out the association of folate genes MTR A2756G and MTRR A66G polymorphisms with the risk of male infertility. The databases of Google Scholar, PubMed, and Science Direct were searched to find relevant studies. Data were extracted from the eligible studies and were analyzed for pooled up odds ratio (OR) with 95% confidence interval (CI). Review Manager 5.4 was used for statistical analysis. Nineteen case-control studies were included in this meta-analysis which comprised 3621 cases and 3327 controls. Pooled analysis revealed that there is a significant association between MTR A2756G polymorphism with male infertility except for the dominant model. The ORs and 95% CI for each genetic model were as follows: 1.21 [1.03-1.42] for the allele model (G vs. A), 2.31 [1.38-3.96] for the additive model (GG vs. AA), 1.17 [0.98-1.38] for the dominant model (GG+AG vs. AA) and 2.10 [1.55-2.86] for the recessive model (GG vs. AG+AA). MTRR A66G has no noticeable association with male infertility. The current meta-analysis suggests that MTR A2756G polymorphism might be a potential risk factor for male infertility. In the future, the sample size should be increased to confirm the present results.

The Impact of Herpes Simplex Virus on Semen Parameters in Men with Idiopathic Infertility: A Systematic Review.

Infertility due to the male factor is one of the major problems of infertile couples. One of the factors contributing to male infertility could be the herpes simplex virus (HSV). The aim of this systematic review was to evaluate the impact of HSV on semen parameters. This systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Different English and Persian databases including Web of Science, PubMed, Scopus, Cochrane Library, EMBASE, ProQuest as well as SID, Magiran and Iranmedex were searched by two researchers, independently, without time limit until April 15, 2022. Observational studies that reported the relationship between HSV and semen parameters in men with idiopathic infertility were included in this review. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment of the included studies. Out of 356 retrieved articles, 12 observational studies comprising a total of 1460 patients were reviewed. Four studies examined the effect of HSV1 virus, two studies examined the effect of HSV2 virus and five studies examined the effect of both viruses on semen parameters. Seven studies reported at least one significant association between HSV infection and semen parameters. Sperm count and sperm motility were semen parameters further affected by the virus. In conclusion, HSV can be one of the risk factors for male infertility and it can affect semen parameters. However, due to the dearth of studies, further research with more robust designs are recommended.

Nickel oxide nanoparticles exposure as a risk factor for male infertility: "In vitro" effects on porcine pre-pubertal Sertoli cells.

Lately, nickel oxide nanoparticles (NiO NPs) have been employed in different industrial and biomedical fields. Several studies have reported that NiO NPs may affect the development of reproductive organs inducing oxidative stress and, resulting in male infertility. We investigated the in vitro effects of NiO NPs on porcine pre-pubertal Sertoli cells (SCs) which undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposure at two subtoxic doses of NiO NPs of 1 μg/ml and 5 μg/ml. After NiO NPs exposure we performed the following analysis: (a) SCs morphological analysis (Light Microscopy); (b) ROS production and oxidative DNA damage, gene expression of antioxidant enzymes (c) SCs functionality (AMH, inhibin B Real-time PCR analysis and ELISA test); (d) apoptosis (WB analysis); (e) pro-inflammatory cytokines (Real-time PCR analysis), and (f) MAPK kinase signaling pathway (WB analysis). We found that the SCs exposed to both subtoxic doses of NiO NPs didn't sustain substantial morphological changes. NiO NPs exposure, at each concentration, reported a marked increase of intracellular ROS at the third week of treatment and DNA damage at all exposure times. We demonstrated, un up-regulation of SOD and HO-1 gene expression, at both concentrations tested. The both subtoxic doses of NiO NPs detected a down-regulation of AMH and inhibin B gene expression and secreted proteins. Only the 5 μg/ml dose induced the activation of caspase-3 at the third week. At the two subtoxic doses of NiO NPs a clear pro-inflammatory response was resulted in an up-regulation of TNF-α and IL-6 in terms of mRNA. Finally, an increased phosphorylation ratio of p-ERK1/2, p-38 and p-AKT was observed up to the third week, at both concentrations. Our results show the negative impact of subtoxic doses NiO NPs chronic exposure on porcine SCs functionality and viability.

Role of MDR1 Gene Polymorphisms in Human Male Infertility: A Meta-Analysis.

The present meta-analysis is performed to determine the association of C1236T and C3435T polymorphisms in the MDR1 gene. Google Scholar, PubMed, and Science Direct were searched. A total of 47 studies were retrieved, of which only three case-control studies, consisting of 490 cases and 423 controls, met the selection criteria. Odds ratios (ORs) for MDR1 C1236T were as follows: Allelic model (T vs. C): OR = 1.06 [0.83, 1.35]; Additive model (TT vs. CC): OR = 0.91 [0.53, 1.56]; Dominant model (TT+CT vs. CC): OR = 0.83 [0.55, 1.24]; and Recessive model (TT vs. CT+CC): OR = 1.43 [0.95, 2.17]. However, for MDR1 C3435T: Allelic model (T vs. C): OR = 1.06 [0.83, 1.35]; Additive model (TT vs. CC): OR = 1.18 [0.75, 1.88]; Dominant model (TT+CT vs. CC): OR = 1.42 [0.99, 2.04]; and Recessive model (TT vs. CT+CC): OR = 0.90 [0.61, 1.33]. None of the four models presented a significant association of either polymorphism with the risk of infertility in men (p >.05). The present study indicates that MDR1 gene polymorphisms might not be a risk factor for male infertility. Further studies with a larger sample size are needed to be conducted to confirm the findings of the present study.

Identification of a Methylation Pattern in the SNRPN Gene Promoter and its Association with Semen Abnormality Among Iraqi Males

Infertility considered as a multifactorial condition; the small nuclear ribonucleoprotein polypeptide N (SNRPN) gene is an imprinted gene. However, abnormal imprinting of this gene due to the methylation may result in abnormal function or silencing of the gene. Main aim of this study is to investigate the methylation present at the promoter of (SNRPN) gene and its role as a risk factor for male infertility. Sixty- three infertile males with age mean (32.28 ± 6.88 years) and 13 fertile males as a control age mean (34.07 ± 6.52 years) were investigated. Whole genomic DNA was extracted, DNA integrity was checked using β-globin gene as an internal control. The targeted region was amplified by polymerase chain reaction (PCR) technique. In addition, the SNRPN gene's promoter methylation was qualitatively detected using Real time polymerase chain reaction (qPCR) utilizing two sets of primers: methylated and un-methylated. Results reveled that all of the 63 infertile males were experiencing decrease in sperm concentration 9.42 ± 8.70 million/ml, reduced progressive motility 2.89 ± 5.45% as well as strange sperm morphology 27.06 ± 16.50%, while the values in the control group are normal. The results of the current investigation showed that the promoter of SNRPN was hypermethylated in some samples 22.7%, somewhat methylated in others 20.4%, and unmethylated in other samples 56.8% from infertile samples, while none of the 13 control samples had any methylation. These findings suggest that SNRPN gene may be associated with the negative changes in semen parameters, which could lead to male infertility.