Impact of heavy alcohol consumption and cigarette smoking on sperm DNA integrity

The purposes of the presents study were to investigate the impact of alcohol consumption and cigarette smoking on semen parameters and sperm DNA quality, as well as to determine whether tobacco smoking, or alcohol consumption causes more deterioration of sperm quality. Two hundred and eleven semen samples of men were included in this study. Four groups were studied: heavy smokers (N = 48), heavy drinkers (N = 52), non-smokers (n = 70), and non-drinkers (n = 41). Semen parameters were determined according to WHO guidelines, protamine deficiency assessed by chromomycin (CMA3) staining, and sperm DNA fragmentation (sDF) evaluated by TUNEL assay. Sperm parameters were significantly higher in non-smokers versus smokers and in non-drinkers versus drinkers (p < 0.005). However, protamine deficiency and sDF were significantly lower in non-smokers versus smokers and in non-drinkers versus drinkers (p < 0.0001). No significant difference in the semen analysis parameters was observed between heavy smokers and heavy drinkers (semen volume: 3.20 ± 1.43 vs. 2.81 ± 1.56 ml, semen count: 65.75 ± 31.32 vs. 53.51 ± 32.67 mill/ml, total motility: 24.27 ± 8.18 vs. 23.75 ± 1.75%, sperm vitality: 36.15 ± 18.57 vs. 34.62 ± 16.65%, functional integrity: 41.56 ± 18.57 vs. 45.96 ± 17.98% and the morphologically normal spermatozoa: 28.77 ± 11.82 vs. 27.06 ± 13.13%, respectively). However, protamine deficiency was significantly higher among drinkers than smokers (37.03 ± 9.75 vs. 33.27 ± 8.56%, p = 0.020). The sDF was also significantly higher among drinkers than smokers (22.37 ± 7.60 vs. 15.55 ± 3.33%, p < 0.0001). Thus, cigarette smoking, and heavy alcohol intake can deteriorate sperm quality. However, alcohol consumption deteriorates sperm maturity and damages DNA integrity at significantly higher rates than cigarette smoking

The Impact of Heavy Smoking on Male Infertility and Its Correlation with the Expression Levels of the PTPRN2 and PGAM5 Genes

Smoking has been linked to male infertility by affecting the sperm epigenome and genome. In this study, we aimed to determine possible changes in the transcript levels of PGAM5 (the phosphoglycerate mutase family member 5), PTPRN2 (protein tyrosine phosphatase, N2-type receptor), and TYRO3 (tyrosine protein kinase receptor) in heavy smokers compared to non-smokers, and to investigate their association with the fundamental sperm parameters. In total, 118 sperm samples (63 heavy-smokers (G1) and 55 non-smokers (G2)) were included in this study. A semen analysis was performed according to the WHO guidelines. After a total RNA extraction, RT-PCR was used to quantify the transcript levels of the studied genes. In G1, a significant decrease in the standard semen parameters in comparison to the non-smokers was shown (p < 0.05). Moreover, PGAM5 and PTPRN2 were differentially expressed (p ≤ 0.03 and p ≤ 0.01, respectively) and downregulated in the spermatozoa of G1 compared to G2. In contrast, no difference was observed for TYRO3 (p ≤ 0.3). In G1, the mRNA expression level of the studied genes was correlated negatively with motility, sperm count, normal form, vitality, and sperm membrane integrity (p < 0.05). Therefore, smoking may affect gene expression and male fertility by altering the DNA methylation patterns in the genes associated with fertility and sperm quality, including PGAM5, PTPRN2, and TYRO3

Impact of tobacco smoking in association with H2BFWT, PRM1 and PRM2 genes variants on male infertility

Tobacco's genotoxic components can cause a wide range of gene defects in spermatozoa such as single- or double-strand DNA breaks, cross-links, DNA-adducts, higher frequencies of aneuploidy and chromosomal abnormalities. The aim in this study was to determine the correlation between sperm quality determined by standard parameters, sperm DNA maturity tested by Chromomycin A3 (CMA3) staining, sperm DNA fragmentation tested by TUNEL assay and tobacco smoking in association with the single nucleotides polymorphisms (SNP) of three nuclear protein genes in spermatozoa (H2BFWT, PRM1 and PRM2). In this study, semen samples of 167 male patients were collected and divided into 54 non-smokers and 113 smokers. The target sequences in the extracted sperm DNA were amplified by PCR followed by Sanger sequencing. The results showed the presence of three variants: rs7885967, rs553509 and rs578953 in H2BFWT gene in the study population. Only one variant rs737008 was detected in PRM1 gene, and three variants were detected in the PRM2 gene: rs2070923, rs1646022 and rs424908. No significant association was observed between the concentration, progressive motility, morphology and the occurrence of H2BFWT, PRM1 and PRM2 SNPs. However, sperm parameters were significantly lower in heavy smokers compared to controls (p < 0.01) (sperm count: 46.00 vs. 78.50 mill/ml, progressive motility: 15.00% vs. 22.00%, and morphology 4.00% vs. 5.00%, respectively). Moreover, the heavy smoker individuals exhibited a considerable increase in CMA3 positivity and sDF compared to non-smokers (p < 0.01) (29.50% vs. 20.50% and 24.50% vs. 12.00%, respectively). In conclusion, smoking altered sperm parameters and sperm DNA integrity, but did not show a linkage with genetic variants in H2BFWT, and protamine genes (PRM1 and PRM2)

Female Fertility Preservation: Different Interventions and Procedures

A human being is made up of two living cells: the egg and the sperm, which pass the torch of life to the next generation. After zygote, the fertilized egg undergoes a series of mitotic divisions. First division into two cells is called blastomeres, and then four cells to 64 cells are called the morula stage. Five days after fertilization, the embryo reaches the blastocyst stage. This blastocyst is attaching itself to the uterine wall for implantation. Implantation is complete when the blastocyst is fully embedded in the endometrium a few days later. Cryopreservation of ovarian tissue, oocytes, embryos, and blastocysts has become an integral part of improving the success of infertility treatment and fertility preservation. Various cryopreservation strategies have been proposed to enhance cell survival and preserve cellular function. It also increases the efficiency of assisted reproductive technology (ART) procedures, enables biodiversity conservation, and provides protection to a valuable biological material. However, successful cryopreservation requires the use of cryoprotectants. The chemical and physical effects of these reagents/processes cause extensive cryogenic damage to the plasma membrane, leading to changes in its normal function. In this chapter, we will discuss different interventions to preserve fertility, including cryopreservation methods and cryoprotectants used

Role of Antioxidants Supplementation in the Treatment of Male Infertility

Nutritional utilization of antioxidants, such as vitamins C, E, ß-Carotene and micronutrients, such as folate and zinc, have been shown to be critically essential for normal semen quality and reproductive function. However, it is still, a large knowledge gap exists concerning the role of antioxidants on semen parameters and the role in treatment of male subfertility. Therefore, the current review article designed to find out the positive effect of antioxidants on semen quality, alterations in physiological functions of spermatozoa and infertility treatment It is advisable that patients with oxidative DNA disruption should be asked to take a simple course of antioxidants prior to undertaking assisted reproduction treatment (ART). In conclusion, antioxidant may be employed as a potent antioxidant and may improve infertility treatment outcomes with ART

Seminiferous Tubules and Spermatogenesis

One of the major concerns of the world health community is the infertility. The definition of infertility according to the World Health Organization (WHO) and the American Society for Reproductive Medicine (ASRM) is the inability of a healthy couple to achieve a conception after one year of regular, unprotected intercourse. Fertility complications affect seven percent of the male. The causes of infertility were divided to non-obstructive and obstructive. But, in almost 75% of male infertility cases are idiopathic with predominance of the genetic abnormalities. Numerical or structural chromosomal abnormalities are considered as genetic abnormalities that occur during the meiotic division in spermatogenesis. These abnormalities get transferred to the Offspring, which affects the normal and even the artificial conception. In the human reproduction, sperm cells are considered as a delivery vehicle for the male genetic material packed in chromosomes, which are composed of nearly 2-meter Deoxyribonucleic acid (DNA) molecule and their packaging proteins. This chapter points to grant a summarized description of individual components of the male reproductive system: the seminiferous tubule and spermatogenesis. Here, we describe step by step the structure of the testis seminiferous tubule and what occurs inside these tubules like cell communication and germ cell development from spermatogonia until spermatozoon. This book chapter is very useful for the biologists and physicians working in Assisted reproduction field to understand the physiology and pathology of spermatogenesis

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES: Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research