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Afterword: An update on clinical utility and diagnostic value of various andrological techniques

Durairajanayagam D, Agarwal A, Baskaran S, Vij S

Andrologia, 2021 Mar;53(2):e13819.
PMID: 33620116 DOI: 10.1111/and.13819
Matched MeSH terms: Spermatozoa/metabolism
A preliminary study of reactive oxygen species activity within motile Boer buck sperm using confocal laser scanning microscope (CLSM)

Fatimah IS, Iswadi IM, Khairul O, Nurhazilah M, Fadzilah MS, Padzil AR, et al.

Clin Ter, 2010;161(2):125-8.
PMID: 20499025

There is an association between reactive oxygen species (ROS) and DNA damage to sperm. Researchers believe that ROS is always present at the sperm's head. The variation of ROS concentration within the area has an impact on the integrity of the DNA.

Matched MeSH terms: Spermatozoa/metabolism*
Causes and consequences of sperm mitochondrial dysfunction

Durairajanayagam D, Singh D, Agarwal A, Henkel R

Andrologia, 2021 Feb;53(1):e13666.
PMID: 32510691 DOI: 10.1111/and.13666

Mitochondria have multiple functions, including synthesis of adenine triphosphate, production of reactive oxygen species, calcium signalling, thermogenesis and apoptosis. Mitochondria have a significant contribution in regulating the various physiological aspects of reproductive function, from spermatogenesis up to fertilisation. Mitochondrial functionality and intact mitochondrial membrane potential are a pre-requisite for sperm motility, hyperactivation, capacitation, acrosin activity, acrosome reaction and DNA integrity. Optimal mitochondrial activity is therefore crucial for human sperm function and semen quality. However, the precise role of mitochondria in spermatozoa remains to be fully explored. Defects in sperm mitochondrial function severely impair the maintenance of energy production required for sperm motility and may be an underlying cause of asthenozoospermia. Sperm mtDNA is susceptible to oxidative damage and mutations that could compromise sperm function leading to infertility. Males with abnormal semen parameters have increased mtDNA copy number and reduced mtDNA integrity. This review discusses the role of mitochondria in sperm function, along with the causes and impact of its dysfunction on male fertility. Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.

Matched MeSH terms: Spermatozoa/metabolism
Deficiency in Sperm-Egg Protein Interaction as a Major Cause of Fertilization Failure

Sabetian S, Shamsir MS

J. Membr. Biol., 2017 04;250(2):133-144.
PMID: 28280854 DOI: 10.1007/s00232-017-9954-1

Complete elucidation of fertilization process at molecular level is one of the unresolved challenges in sexual reproduction studies, and understanding the molecular mechanism is crucial in overcoming difficulties in infertility and unsuccessful in vitro fertilization. Sperm-oocyte interaction is one of the most remarkable events in fertilization process, and deficiency in protein-protein interactions which mediate this interaction is a major cause of unexplained infertility. Due to detection of how the various defects of sperm-oocyte interaction can affect fertilization failure, different experimental methods have been applied. This review summarizes the current understanding of sperm-egg interaction mechanism during fertilization and also accumulates the different types of sperm-egg interaction abnormalities and their association with infertility. Several detection approaches regarding sperm-egg protein interactions and the associated defects are reviewed in this paper.

Matched MeSH terms: Spermatozoa/metabolism*
Functional features and protein network of human sperm-egg interaction

Sabetian S, Shamsir MS, Abu Naser M

Syst Biol Reprod Med, 2014 Dec;60(6):329-37.
PMID: 25222562 DOI: 10.3109/19396368.2014.955896

Elucidation of the sperm-egg interaction at the molecular level is one of the unresolved problems in sexual reproduction, and understanding the molecular mechanism is crucial in solving problems in infertility and failed in vitro fertilization (IVF). Many molecular interactions in the form of protein-protein interactions (PPIs) mediate the sperm-egg membrane interaction. Due to the complexity of the problem such as difficulties in analyzing in vivo membrane PPIs, many efforts have failed to comprehensively elucidate the fusion mechanism and the molecular interactions that mediate sperm-egg membrane fusion. The main purpose of this study was to reveal possible protein interactions and associated molecular function during sperm-egg interaction using a protein interaction network approach. Different databases have been used to construct the human sperm-egg interaction network. The constructed network revealed new interactions. These included CD151 and CD9 in human oocyte that interact with CD49 in sperm, and CD49 and ITGA4 in sperm that interact with CD63 and CD81, respectively, in the oocyte. These results showed that the different integrins in sperm may be involved in human sperm-egg interaction. It was also suggested that sperm ADAM2 plays a role as a protein candidate involved in sperm-egg membrane interaction by interacting with CD9 in the oocyte. Interleukin-4 receptor activity, receptor signaling protein tyrosine kinase activity, and manganese ion transmembrane transport activity are the major molecular functions in sperm-egg interaction protein network. The disease association analysis indicated that sperm-egg interaction defects are also reflected in other disease networks such as cardiovascular, hematological, and breast cancer diseases. By analyzing the network, we identified the major molecular functions and disease association genes in sperm-egg interaction protein. Further experimental studies will be required to confirm the significance of these new computationally resolved interactions and the genetic links between sperm-egg interaction abnormalities and the associated disease.

Matched MeSH terms: Spermatozoa/metabolism*
Fulltext Comparative analysis of Mafriwal (Bos taurus × Bos indicus) and Kedah Kelantan (Bos indicus) sperm proteome identifies sperm proteins potentially responsible for higher fertility in a tropical climate

Ashrafzadeh A, Nathan S, Karsani SA

Int J Mol Sci, 2013;14(8):15860-77.
PMID: 23903046 DOI: 10.3390/ijms140815860

The fertility of zebu cattle (Bos indicus) is higher than that of the European purebred (Bos taurus) and crossbred (Bos taurus × Bos indicus) cattle in tropical areas. To identify proteins related to the higher thermo-tolerance and fertility of Zebu cattle, this study was undertaken to identify differences in sperm proteome between the high fertile Malaysian indigenous zebu cattle (Kedah Kelantan) and the sub-fertile crossbred cattle (Mafriwal). Frozen semen from three high performance bulls from each breed were processed to obtain live and pure sperm. Sperm proteins were then extracted, and two-dimensional gel electrophoresis performed to compare proteome profiles. Gel image analysis identified protein spots of interest which were then identified by liquid chromatography mass spectrometry quadrupole time-of-flight (LC MS/MS Q-TOF). STRING network analysis predicted interactions between at least 20 of the identified proteins. Among the identified proteins, a number of motility and energy related proteins were present in greater abundance in Kedah Kelantan. Sperm motility evaluation by Computer Assisted Semen Analysis (CASA) confirmed significantly higher motility in Kedah Kelantan. While results from this study do identify proteins that may be responsible for the higher fertility of Kedah Kelantan, functional characterization of these proteins is warranted to reinforce our understanding of their roles in sperm fertility.

Matched MeSH terms: Spermatozoa/metabolism*
Aberrant Upregulation of Compensatory Redox Molecular Machines May Contribute to Sperm Dysfunction in Infertile Men with Unilateral Varicocele: A Proteomic Insight

Swain N, Samanta L, Agarwal A, Kumar S, Dixit A, Gopalan B, et al.

Antioxid Redox Signal, 2020 03 10;32(8):504-521.
PMID: 31691576 DOI: 10.1089/ars.2019.7828

Aims:
To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach.
Results:
Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group. Ingenuity pathway analysis (IPA) predicted suppression of oxidative phosphorylation (OXPHOS) (validated by Western blotting [WB]) along with augmentation in OS and mitochondrial dysfunction in UV. The top affected networks indicated by IPA involved heat shock proteins (HSPs: HSPA2 and HSP90B1). Their expression profile was corroborated by immunocytochemistry and WB. Hypoxia-inducible factor 1A as an upstream regulator of HSPs was predicted by MetaCore. Occurrence of reductive stress in UV spermatozoa was corroborated by thiol redox status.
Innovation:
This is the first evidence of a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction.
Conclusions:
Upregulation of antioxidant system and dysfunctional OXPHOS would have shifted the redox balance of biological redox couples (GSH/GSSG, NAD+/NADH, and NADP+/NADPH) to a more reducing state leading to reductive stress. Chronic reductive stress-induced OS may be involved in sperm dysfunction in infertile men with UV, where the role of HSPs cannot be ignored. Intervention with antioxidant therapy warrants proper prior investigation.

Matched MeSH terms: Spermatozoa/metabolism*
Fulltext Mammalian sperm fertility related proteins

Ashrafzadeh A, Karsani SA, Nathan S

Int J Med Sci, 2013;10(12):1649-57.
PMID: 24151436 DOI: 10.7150/ijms.6395

Infertility is an important aspect of human and animal reproduction and still presents with much etiological ambiguity. As fifty percent of infertility is related to the male partner, molecular investigations on sperm and seminal plasma can lead to new knowledge on male infertility. Several comparisons between fertile and infertile human and other species sperm proteome have shown the existence of potential fertility markers. These proteins have been categorized into energy related, structural and other functional proteins which play a major role in sperm motility, capacitation and sperm-oocyte binding. The data from these studies show the impact of sperm proteome studies on identifying different valuable markers for fertility screening. In this article, we review recent development in unraveling sperm fertility related proteins.

Matched MeSH terms: Spermatozoa/metabolism*
The impact of leptin on sperm

Almabhouh FA, Singh HJ

Reprod Fertil Dev, 2023 May;35(8):459-468.
PMID: 37196661 DOI: 10.1071/RD22222

Despite its important role in numerous physiological functions, including regulation of appetite and body weight, immune function and normal sexual maturation, raised leptin levels could result in significant damaging effects on sperm. The adverse effects of leptin on the male reproductive system result from its direct actions on the reproductive organs and cells instead of the hypothalamus-pituitary-gonadal axis. Binding of leptin to the receptors in the seminiferous tubular cells of the testes increases free radical production and decreases the gene expression and activity of endogenous enzymatic antioxidants. These effects are mediated via the PI3K pathway. The resultant oxidative stress causes significant damage to the seminiferous tubular cells, germ cells and sperm DNA leading to apoptosis, increased sperm DNA fragmentation, decreased sperm count, increased fraction of sperm with abnormal morphology, and decreased seminiferous tubular height and diameter. This review summarises the evidence in the literature on the adverse effects of leptin on sperm, which could underlie the often-reported sperm abnormalities in obese hyperleptinaemic infertile males. Although leptin is necessary for normal reproductive function, its raised levels could be pathologic. There is, therefore, a need to identify the cut-off level in the serum and seminal fluid above which leptin becomes pathological for better management of leptin associated adverse effects on male reproductive function.

Matched MeSH terms: Spermatozoa/metabolism
Effect of antioxidants on post thaw microscopic, oxidative stress parameter and fertility of Boer goat spermatozoa in Tris egg yolk glycerol extender

Memon AA, Wahid H, Rosnina Y, Goh YM, Ebrahimi M, Nadia FM

Anim. Reprod. Sci., 2012 Dec;136(1-2):55-60.
PMID: 23182473 DOI: 10.1016/j.anireprosci.2012.10.020

This study was conducted to determine the effect of antioxidants on standard semen parameters, lipid peroxidation and fertility of Boer goat semen after cryopreservation. Ejaculates from four bucks were collected, evaluated and pooled at 37°C. The pooled semen was diluted with Tris citric acid fructose for washing. Semen samples, which were diluted with a Tris-based extender containing the antioxidant ascorbic acid (8.5mg/ml), butylated hydroxytoluene (2mM), cysteine (5mM) and hypotaurine (10mM) and an extender without antioxidant supplementation were cooled to 4°C and frozen in 0.25 straws with programmable freezer and finally stored in liquid nitrogen. Data (10 replicates) were analyzed by one-way analysis of variance. Mean (±SEM) progressive motility was significantly higher in ascorbic acid than other supplement groups and control samples (P>0.05). Best values were observed in ascorbic acid followed by BHT, cysteine, and hypotaurine. Antioxidant supplementation in extender showed significant (P<0.05) better values than the control group for sperm membrane integrity, acrosome integrity and viability. The ability of antioxidants to reduce the lipid peroxidation (LPO) after freeze thawing was measured by the formation of malondialdehyde (MDA) using the thiobarbituric acid method. Results showed that addition of antioxidants significantly reduced the rate of LPO in comparison to control (P<0.05). Ascorbic acid exhibited better values (1.27±0.28), than butylated hydroxytoluene, cysteine and hypotaurine 1.32±0.42, 2.27±0.16 and 2.38±0.17 respectively, which are significantly better than control (3.52±0.54). Higher pregnancy rate was observed with ascorbic acid followed by butylated hydroxtolune, hypotaurine and cysteine. However, differences in the fertility rate were non-significant with hypotaurine, cysteine and control groups.

Matched MeSH terms: Spermatozoa/metabolism
Proteomics, oxidative stress and male infertility

Agarwal A, Durairajanayagam D, Halabi J, Peng J, Vazquez-Levin M

Reprod Biomed Online, 2014 Jul;29(1):32-58.
PMID: 24813754 DOI: 10.1016/j.rbmo.2014.02.013

Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility. Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free radicals. A variety of sperm and seminal plasma proteins were found to be expressed either in abundance (over-expressed) or in a lesser amount (underexpressed), while other proteins were found to be unique either to men with oxidative stress or to men with a balanced ratio of antioxidants/free radicals. Each study included in this review suggested several proteins that could possibly act as biomarkers of oxidative stress-induced male infertility, such as protein DJ-1, PIP, lactotransferrin and peroxiredoxin. Pathway analysis performed in these studies revealed that the changes in seminal plasma proteins in men with oxidative stress could be attributed to stress responses and regulatory pathways, while changes in sperm proteins were linked to stress responses and metabolic responses. Subsequent studies could look into post-translational modifications in the protein profile of men with idiopathic infertility. We hope that the information in this review will contribute to a better understanding of the main causes of idiopathic male infertility.

Matched MeSH terms: Spermatozoa/metabolism
Adverse effects of leptin on histone-to-protamine transition during spermatogenesis are prevented by melatonin in Sprague-Dawley rats

Almabhouh FA, Singh HJ

Andrologia, 2018 Feb;50(1).
PMID: 28497500 DOI: 10.1111/and.12814

This study examines the effect of melatonin on leptin-induced changes in transition of histone to protamine in adult rats during spermatogenesis. Twelve-week-old Sprague-Dawley rats were randomised into control, leptin-, leptin-melatonin-10-, leptin-melatonin-20- and melatonin-10-treated groups with six rats per group. Leptin was given via intraperitoneal injections (i.p.) daily for 42 days (60 μg/kg body weight). Rats in the leptin- and melatonin-treated groups were given either 10 or 20 mg day-1 kg-1 body weight of leptin in drinking water. Melatonin-10-treated group received only 10 mg of melatonin day-1 kg-1 body weight in drinking water for 42 days. Control rats received 0.1 ml of 0.9% saline. Upon completion of the treatment, sperm count, morphology and histone-to-protamine ratio were estimated. Gene expression of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1, PRM2, TNP1 and TNP2 was determined. Data were analysed using ANOVA. Sperm count was significantly lower, whereas the fraction of spermatozoa with abnormal morphology, the ratio of histone-to-protamine transition and the expressions of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1 were significantly higher in leptin-treated rats than those in controls or melatonin-treated rats. It appears that exogenous leptin administration adversely affects histone-to-protamine transition, which is prevented by concurrent administration of melatonin.

Matched MeSH terms: Spermatozoa/metabolism
Fulltext Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome

Shi W, Louzada S, Grigorova M, Massaia A, Arciero E, Kibena L, et al.

Hum Mol Genet, 2019 Aug 15;28(16):2785-2798.
PMID: 31108506 DOI: 10.1093/hmg/ddz101

Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10-3 (95% CI 1.94 × 10-3 to 2.48 × 10-3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.

Matched MeSH terms: Spermatozoa/metabolism
Fulltext α-Linolenic acid supplementation in BioXcell® extender can improve the quality of post-cooling and frozen-thawed bovine sperm

Kaka A, Wahid H, Rosnina Y, Yimer N, Khumran AM, Sarsaifi K, et al.

Anim. Reprod. Sci., 2015 Feb;153:1-7.
PMID: 25544152 DOI: 10.1016/j.anireprosci.2014.12.001

The present study was conducted to determine the effects of supplementing α-linolenic acid (ALA) into BioXcell(®) extender on post-cooling, post-thawed bovine spermatozoa and post thawed fatty acid composition. Twenty-four semen samples were collected from three bulls using an electro-ejaculator. Fresh semen samples were evaluated for general motility using computer assisted semen analyzer (CASA) whereas morphology and viability with eosin-nigrosin stain. Semen samples extended into BioXcell(®) were divided into five groups to which 0, 3, 5, 10 and 15 ng/ml of ALA were added, respectively. The treated samples were incubated at 37°C for 15 min for ALA uptake by sperm cells before being cooled for 2 h at 5°C. After evaluation, the cooled samples were packed into 0.25 ml straws and frozen in liquid nitrogen for 24 h before thawing and evaluation for semen quality. Evaluation of cooled and frozen-thawed semen showed that the percentages of all the sperm parameters improved with 5 ng/ml ALA supplement. ALA was higher in all treated groups than control groups than control group. In conclusion, 5 ng/ml ALA supplemented into BioXcell(®) extender improved the cooled and frozen-thawed quality of bull spermatozoa.

Matched MeSH terms: Spermatozoa/metabolism
Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality

Darbandi M, Darbandi S, Agarwal A, Baskaran S, Dutta S, Sengupta P, et al.

J Assist Reprod Genet, 2019 Feb;36(2):241-253.
PMID: 30382470 DOI: 10.1007/s10815-018-1350-y

PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS

Matched MeSH terms: Spermatozoa/metabolism
Fulltext Melatonin ameliorates the adverse effects of leptin on sperm

Almabhouh FA, Osman K, Ibrahim SF, Gupalo S, Gnanou J, Ibrahim E, et al.

Asian J Androl, 2016 10 18;19(6):647-654.
PMID: 27748315 DOI: 10.4103/1008-682X.183379

This study examined the effects of melatonin on leptin-induced changes in sperm parameters in adult rats. Five groups of Sprague-Dawley rats were treated with either leptin or leptin and melatonin or melatonin for 6 weeks. Leptin was given daily via the intraperitoneal route (60 μg kg-1 body weight) and melatonin was given in drinking water (10 mg kg-1 or 20 mg kg-1 body weight per day). Upon completion, sperm count, sperm morphology, 8-hydroxy-2-deoxyguanosine, Comet assay, TUNEL assay, gene expression profiles of antioxidant enzymes, respiratory chain reaction enzymes, DNA damage, and apoptosis genes were estimated. Data were analyzed using ANOVA. Sperm count was significantly lower whereas the fraction of sperm with abnormal morphology, the level of 8-hydroxy-2-deoxyguanosine, and sperm DNA fragmentation were significantly higher in rats treated with leptin only. Microarray analysis revealed significant upregulation of apoptosis-inducing factor, histone acetyl transferase, respiratory chain reaction enzyme, cell necrosis and DNA repair genes, and downregulation of antioxidant enzyme genes in leptin-treated rats. Real-time polymerase chain reaction showed significant decreases in glutathione peroxidase 1 expression with increases in the expression of apoptosis-inducing factor and histone acetyl transferase in leptin-treated rats. There was no change in the gene expression of caspase-3 (CASP-3). In conclusion, the adverse effects of leptin on sperm can be prevented by concurrent melatonin administration.

Matched MeSH terms: Spermatozoa/metabolism
Fenitrothion alters sperm characteristics in rats: ameliorating effects of palm oil tocotrienol-rich fraction

Taib IS, Budin SB, Ghazali AR, Jayusman PA, Mohamed J

Exp Anim, 2014;63(4):383-93.
PMID: 25030881

Exposure to organophosphate insecticides such as fenitrothion (FNT) in agriculture and public health has been reported to affect sperm quality. Antioxidants may have a potential to reduce spermatotoxic effects induced by organophosphate. The present study was carried out to evaluate the effects of palm oil tocotrienol-rich fraction (TRF) in reducing the detrimental effects occurring in spermatozoa of FNT-treated rats. Adult male Sprague-Dawley rats were divided into four equal groups: a control group and groups of rats treated orally with palm oil TRF (200 mg/kg), FNT (20 mg/kg) and palm oil TRF (200 mg/kg) combined with FNT (20 mg/kg). The sperm characteristics, DNA damage, superoxide dismutase (SOD) activity, and levels of reduced glutathione (GSH), malondialdehyde (MDA), and protein carbonyl (PC) were evaluated. Supplementation with TRF attenuated the detrimental effects of FNT by significantly increasing the sperm counts, motility, and viability and decreased the abnormal sperm morphology. The SOD activity and GSH level were significantly increased, whereas the MDA and PC levels were significantly decreased in the TRF+FNT group compared with the rats receiving FNT alone. TRF significantly decreased the DNA damage in the sperm of FNT-treated rats. A significant correlation between abnormal sperm morphology and DNA damage was found in all groups. TRF showed the potential to reduce the detrimental effects occurring in spermatozoa of FNT-treated rats.

Matched MeSH terms: Spermatozoa/metabolism
Fulltext Aging Induces Profound Changes in sncRNA in Rat Sperm and These Changes Are Modified by Perinatal Exposure to Environmental Flame Retardant

Suvorov A, Pilsner JR, Naumov V, Shtratnikova V, Zheludkevich A, Gerasimov E, et al.

Int J Mol Sci, 2020 Nov 04;21(21).
PMID: 33158036 DOI: 10.3390/ijms21218252

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father's sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats. We also analyze the modification of these changes by exposure to environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). sncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. The distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. In total, 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (twofold change, false discovery rate (FDR) p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, while piRNA were enriched for long terminal repeat (LTR) targets. BDE-47 accelerated age-dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposure.

Matched MeSH terms: Spermatozoa/metabolism*
Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility

Samanta L, Agarwal A, Swain N, Sharma R, Gopalan B, Esteves SC, et al.

J Urol, 2018 08;200(2):414-422.
PMID: 29530785 DOI: 10.1016/j.juro.2018.03.009

PURPOSE: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility.
MATERIALS AND METHODS: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured.
RESULTS: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele.
CONCLUSIONS: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients.

Matched MeSH terms: Spermatozoa/metabolism*
Fulltext Chlorophytum borivilianum (Safed Musli) root extract prevents impairment in characteristics and elevation of oxidative stress in sperm of streptozotocin-induced adult male diabetic Wistar rats

Giribabu N, Kumar KE, Rekha SS, Muniandy S, Salleh N

BMC Complement Altern Med, 2014;14:291.
PMID: 25104050 DOI: 10.1186/1472-6882-14-291

We hypothesized that C. borivilianum root, known to improve male reproductive performance, prevents impairment in characteristics, morphology and elevation of oxidative stress in sperm of diabetics. We therefore investigated the effect of aqueous root extract of C. borivilianum on these parameters in diabetic rat model.

Matched MeSH terms: Spermatozoa/metabolism

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