The epigenetic approach of varicocele: a focus on sperm DNA and m6A-RNA methylation.

Background: Varicocele is an abnormal dilation and torsion of the pampiniform venous plexus in the scrotum due to venous reflux, primarily affecting the left side. It affects 15% of men and is a prevalent contributor to male infertility. Varicocele is a complex disorder influenced by genetic, epigenetic, and environmental factors.

Alterations Expression of Key RNA Methylation (m6A) Enzymes in Testicular Tissue of Rats with Induced Varicocele.

Epigenetics impacts male fertility and reproductive disorders. RNA modifications, like m6A, influence RNA metabolism. Varicocele contributes to male infertility, and oxidative stress affects sperm function.

Protective effects of alpha-lipoic acid and alagebrium chloride against testicular dysfunction induced by varicocele and advanced glycation end (AGE) - Rich diet in a rat mode.

Heat stress from varicocele can heighten oxidative stress in the testes, impacting sperm function and male fertility. Antioxidant therapy is explored as a remedy for varicocele, while dietary factors like processed foods, sugar, and saturated fats correlate with male infertility. Advanced glycation end products (AGEs), generated through glycation processes, can provoke oxidative stress, inflammation, and adverse health consequences.

Effects of Acute Exposure to Methylglyoxal or/and A Diet Rich in Advanced Glycation End Products on Sperm Parameters in Mice.

Background: Advanced glycation end products (AGEs) that accompany many metabolic disorders including diabetes, obesity, and a wide range of dyslipidemia conditions, are strongly associated with adverse effects on cell and tissue homeostasis. Accordingly, our objective was to investigate the impact of AGE-promoting diets on mouse models, considering both scenarios with and without methylglyoxal (MGO) as a primary precursor of AGEs.

Materials And Methods: In this experimental study, 5-week-old C57BL/6 mice were split into four groups as a control group (n=5), AGE (n=5), MGO (n=8), and AGE-MGO-diets (n=8).

Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function.

In this article published in Cell J, Vol 26, No 1, 2024, on pages 81-90, the authors found that the affiliation of authors in address 1 and also the two corresponding authors had accidentally missed during the formatting of the paper. Therefore, we corrected them. The authors would like to apologize for any inconvenience.

Sperm Parameters and Chromatin Integrity in Men Suffering from Celiac Disease: Insights into Reproductive Health, Case-Control Study.

Objective: Celiac disease is a common chronic inflammatory condition of the small intestine caused by permanent intolerance to gluten/gliadin. It has been demonstrated that oxidative stress is one of the mechanisms that is involved in gliadin toxicity, and there is a correlation between oxidative damage with this disease. Similarly, increased oxidative stress was repeatedly reported in infertile men which led to low-quality of sperm function.

Effect of Advanced Glycation end Products (AGEs) on Sperm Parameters and Function in C57Bl/6 Mice.

This study investigated the deleterious impact of advanced glycation end products (AGEs), commonly present in metabolic disorders like diabetes, obesity, and infertility-related conditions, on sperm structure and function using a mouse model where AGE generation was heightened through dietary intervention. Five-week-old C57BL/6 mice were divided into two groups, one on a regular diet (control) and the other on an AGE-rich diet. After 13 weeks, various parameters were examined, including fasting blood glucose, body weight, food consumption, sperm parameters and function, testicular superoxide dismutase levels, malondialdehyde content, total antioxidant capacity, Johnson score, AGE receptor (RAGE) content, and carboxymethyl lysine (CML) content.

Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function.

Objective: Diabetic men suffer an increased risk of infertility associated with signs of oxidative damage and decreased methylation in sperm pointing to a deficit of the one-carbon cycle (1CC). We aimed to investigate this deficit using mice models (type 1 and 2) of streptozotocin-induced diabetes.

Materials And Methods: In this experimental study, 50 male mice, aged eight weeks, were divided randomly into four groups: sham, control, type 1 diabetes mellitus (DM1), and DM2.

Sperm chromatin structure assay (SCSA) and flow cytometry-assisted TUNEL assay provide a concordant assessment of sperm DNA fragmentation as a function of age in a large cohort of approximately 10,000 patients.

Background: Sperm DNA integrity is increasingly seen as a critical characteristic determining reproductive success, both in natural reproduction and in assisted reproductive technologies (ART). Despite this awareness, sperm DNA and nuclear integrity tests are still not part of routine examinations for either infertile men or fertile men wishing to assess their reproductive capacity. This is not due to the unavailability of DNA and sperm nuclear integrity tests.

The role of the transsulfuration pathway in spermatogenesis of vitamin D deficient mice.

Vitamin D deficiency is a global health problem and has been linked to defective spermatogenesis and male infertility. In this study, we aimed to investigate the main enzymes involved in the transsulfuration pathway of 1-carbon metabolism, and spermatogenesis function. Therefore, sixteen male C57 mice were addressed to a control (standard diet) or vitamin D deficient (VDD) diet for 14 weeks.

Aberrant Expression of TET2 Accounts for DNA Hypomethylation in Varicocele.

Objective: Epigenetic modifications such as DNA methylation play a key role in male infertility etiology. This study aimed to explore the global DNA methylation status in testicular spermatogenic cells of varicocele-induced rats and consider their semen quality, with a focus on key epigenetic marks, namely 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), as well as the mRNA and proteins of ten-eleven translocation (TET) methylcytosine dioxygenases 1-3.

Materials And Methods: In this experimental study, 24 mature male Wistar rats (8 in each group) were assigned amongst the control, sham, and varicocele groups.

Omega 6/Omega 3 Ratio Is High in Individuals with Increased Sperm DNA fragmentation.

An imbalance between omega-6 and omega-3 fatty acids in sperm has been linked with lipid peroxidation and DNA damage in sperm, indicating a possible correlation to fertility potential. This cross-sectional study involved 56 infertile men (aged 25-45), and assessed the relationship between the omega-6 to omega-3 fatty acid ratio in sperm and seminal plasma with sperm DNA fragmentation. Individuals were categorized based on high or low levels of sperm DNA fragmentation according to two tests (TUNEL and SCSA assay less or greater than 10 and 30%, respectively), and their fatty acid composition, as well as sperm functional tests, were analyzed.

Role of Endoplasmic Reticulum Stress in The Male Reproductive System.

Testicular dysfunction, whether linked to varicocele, obesity, diabetes, aging, inflammation, or lifestyle or environmental issues, is frequently accompanied by an accumulation of unfolded or misfolded proteins, indicating impaired endoplasmic reticulum (ER) function. In this review, we examined the Google Scholar, Scopus and PubMed databases (from 2011 to 2022) to support the association of ER stress with defective spermatogenesis in animal models and humans. ER stress, whether in its pro-survival or pro-apoptotic aspect, appears to be closely linked to each studied situation.

Enhancing the Accuracy of Measuring DEP Force Applied on Cells by Considering the Friction Effect.

The Dielectrophoresis (DEP) phenomenon has been widely used for cell separation in recent years. The experimental measurement of the DEP force is one of the concerns of scientists. This research presents a novel method for more accurately measuring the DEP force.

Assisted Oocyte Activation following Intracytoplasmic Sperm Injection: A Sensible Option for Infertile Couples with Severe Teratozoospermia.

The intracytoplasmic sperm injection (ICSI) has significantly improved male factor infertility treatment; however, complete fertilization failure still occurs in 1-5% of ICSI treatment cycles mainly due to oocyte activation failure. It is estimated that around 40-70% of oocyte activation failure is associated with sperm factors after ICSI. Assisted oocyte activation (AOA) as an effective approach to avoid total fertilization failure (TFF) has been proposed following ICSI.

Oxidative Stress and Cell Cycle Arrest in Seminiferous Tubules Nearby Varicose Vessels: New Perspectives from Experimental Varicocele.

Varicocele (VCL) has been shown to induce severe oxidative stress in the testicular tissue resulting in 35% of males with primary infertility. To compare the exacerbating impacts of varicose on oxidative DNA damage and homeostatic antioxidant reactions in the seminiferous tubules (ST), enclosed and far from varicose vessels. Thirty mature Wistar rats were divided into control and VCL-induced groups.

The effect of alpha-lipoic acid on sperm functions in rodent models for male infertility: A systematic review.

In this systematic review, we assessed different studies to evaluate the protective effect of alpha-lipoic acid (ALA), as a multifaceted antioxidant, on sperm functions in rodent models. Four databases were searched to find papers reporting the effect of ALA treatment on animal models of male infertility. Up to December 2022, 11,787 articles were identified to explain the ALA protective effects.

Alpha-Lipoic Acid Supplementation for Male Partner of Couples with Recurrent Pregnancy Loss: A Post hoc analysis in Clinical Trial.

Background: Increased sperm DNA damage is known as one of the causes of recurrent pregnancy loss (RPL) which can be due to increased levels of oxidative stress. Therefore, the aim of this study was to assess the effect of alpha-lipoic acid (ALA) on sperm parameters and sperm functions in couples with a history of RPL.

Materials And Methods: In this post hoc analysis in clinical trial study, a total of 37 couples with RPL (n=12 and n=25 for placebo and ALA groups, respectively) were considered.

L-Carnitine and Pentoxifylline Supplementation Improves Sperm Viability and Motility at Low Temperature.

Background: In infertility clinics, preserving high-quality spermatozoa for a long time is a necessity. Pentoxifylline (PT) and L-carnitine (LC) are effective in improving sperm motility as well as protecting the sperm membrane. The present study aimed to investigate the protective impacts of PT and LC on the quality of the normal sperm motility, protamine content, and viability on prolonged storage for 12 days at 4-6°C.

Alpha-Lipoic Acid Ameliorates Sperm DNA Damage and Chromatin Integrity in Men with High DNA Damage: A Triple Blind Randomized Clinical Trial.

Objective: Evidence suggests the contributory role of oxidative stress (OS) to sperm DNA damage and eventually, male infertility. Antioxidant supplementation has exhibited favorable results regarding seminal OS, sperm DNA damage, and chromatin integrity. We aimed to evaluate the effect of alpha-lipoic acid (ALA) supplementation on semen analysis, sperm DNA damage, chromatin integrity, and seminal/intracellular OS in infertile men with high sperm DNA damage.

Oxidative versus reductive stress: a delicate balance for sperm integrity.

Despite the long-standing notion of "oxidative stress," as the main mediator of many diseases including male infertility induced by increased reactive oxygen species (ROS), recent evidence suggests that ROS levels are also increased by "reductive stress," due to over-accumulation of reductants. Damaging mechanisms, like guanidine oxidation followed by DNA fragmentation, could be observed following reductive stress. Excessive accumulation of the reductants may arise from excess dietary supplementation over driving the one-carbon cycle and transsulfuration pathway, overproduction of NADPH through the pentose phosphate pathway (PPP), elevated levels of GSH leading to impaired mitochondrial oxidation, or as a result NADH accumulation.

Overlapping sperm damages from vitamin B or D deficiency in mice: Insights into the role of clinical supplementations.

In this study, the effect of 14 weeks of standard diet (controls) or folate and vitamin B12-free diet (VBD group) or vitamin D-free diet (VDD group) were assessed on mice testicular function, and sperm function. Vitamin D deprivation caused increased body weight with no effect from VBD confirming the calcium-independent role of vitamin D on body weight homeostasis. The two deprivations caused convergent damages including decreased testosterone, worsened Johnson scores, tubular differentiation index and spermatogenesis index, and serious worsening of sperm parameters and of sperm functional tests (DNA methylation, protamination, DNA damage and lipid peroxidation).