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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: Sperm Motility/physiology
Effect of butylated hydroxytoluene on cryopreservation of Boer goat semen in Tris egg yolk extender

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

Anim. Reprod. Sci., 2011 Nov;129(1-2):44-9.
PMID: 22024366 DOI: 10.1016/j.anireprosci.2011.10.004

The aim of this study was to determine the effect of butylated hydroxytoluene (BHT), a lipid-soluble anti-oxidant added in different concentrations to the Tris egg yolk extenders on semen cytological parameters pre freezing and post thawing (motility, morphology, viability, acrosome integrity and membrane integrity) of Boer goat spermatozoa. A total of 40 ejaculates from four Boer goat bucks were collected using an artificial vagina. Ten replicates of the ejaculates were diluted with a Tris egg yolk based extender which contained various concentrations (0.5mM, 1.0mM, 2.0mM and 3.0mM) of butylated hydroxytoluene while one sample was processed without supplementation of antioxidant and served as control. The diluted semen was cooled at 4°C and loaded into the straw and then stored in liquid nitrogen. It was evident that supplementation of BHT produces positive effect in terms of motility, membrane integrity and acrosome integrity in comparison with the control group in cooled and frozen Boer goat semen. Results showed significant differences in motility, membrane integrity, acrosome integrity and viability of cooled and frozen Boer goat spermatozoa at different concentrations. Motility, membrane integrity, acrosome integrity and viability was significantly higher in all treated groups than the control group (P<0.05) while there was no significant differences (P>0.05) in morphology trait between all group in cooled semen. However, improvement (P<0.05) was observed only in terms of the membrane integrity and acrosome integrity compared to the control and other treated groups in frozen semen. In conclusion, BHT can be used in cryopreservation of Boer goat semen in order to reduce the oxidative stress on spermatozoa.

Matched MeSH terms: Sperm Motility/physiology
Neither male age nor semen parameters influence clinical pregnancy or live birth outcomes from IVF

Mariappen U, Keane KN, Hinchliffe PM, Dhaliwal SS, Yovich JL

Reprod Biol, 2018 Dec;18(4):324-329.
PMID: 30503182 DOI: 10.1016/j.repbio.2018.11.003

Advanced age is an increasing trend for both males and females seeking in vitro fertilization (IVF). This retrospective cohort study investigated the outcomes of 1280 IVF-related treatment cycles, selecting the first treatment for couples utilizing autologous gametes and who underwent single fresh embryo transfer. Males aged 40-49 years had a 52% reduction in normal sperm motility, while it was markedly reduced by 79% at 50 years or older. However, neither semen parameters nor male age were predictive of clinical pregnancy or live birth chance. In a combination of age groups, cases with Younger Females had the greatest chance of successful outcomes and this was independent of having a younger or older male partner. Specifically, Young Female-Young Male combinations (≤ 35 years) were the most likely to succeed in achieving a clinical pregnancy or live birth (OR 2.84, p 35 years, respectively) had a similar increased chance (OR 2.07, p

Matched MeSH terms: Sperm Motility/physiology
Geographical differences in semen characteristics: Comparing semen parameters of infertile men of the United States and Iraq

Palani A, Sengupta P, Agarwal A, Henkel R

Andrologia, 2020 Apr;52(3):e13519.
PMID: 32003032 DOI: 10.1111/and.13519

The declining trend of male fecundity is a major global health and social concern. Among numerous other confounding factors, variations in male fertility parameters in different regions have repeatedly been suggested to be influenced by geographic locations. The impact of overall lifestyle, behavioural patterns, ethnicity, work stress and associated factors upon health differ greatly between developed and developing countries. These factors, individually or in combination, affect male reproductive functions ensuing the discrepancies in semen qualities in connection with geographic variations. However, reports comparing semen characteristics between developed and developing countries are sparse. The present study finds its novelty in presenting a comparison in semen parameters of infertile men in the United States (n = 76) that fairly represents the population of a highly developed region and Iraq (n = 102), the representative of male populations of a developing region. Samples were collected and analysed according to WHO (WHO laboratory manual for the examination and processing of human semen, WHO; 2010) criteria by means of the Mann-Whitney test. The US population demonstrated lower sperm concentration, total count, and total and progressive sperm motility with a higher seminal total antioxidant capacity (TAC) as compared to the Iraqi population. This report encourages further investigations concerning the confounding factors leading to such alterations in semen qualities between these two geographic areas.

Matched MeSH terms: Sperm Motility/physiology
Fulltext Multistage Optimization Using a Modified Gaussian Mixture Model in Sperm Motility Tracking

Alameri M, Hasikin K, Kadri NA, Nasir NFM, Mohandas P, Anni JS, et al.

Comput Math Methods Med, 2021;2021:6953593.
PMID: 34497665 DOI: 10.1155/2021/6953593

Infertility is a condition whereby pregnancy does not occur despite having unprotected sexual intercourse for at least one year. The main reason could originate from either the male or the female, and sometimes, both contribute to the fertility disorder. For the male, sperm disorder was found to be the most common reason for infertility. In this paper, we proposed male infertility analysis based on automated sperm motility tracking. The proposed method worked in multistages, where the first stage focused on the sperm detection process using an improved Gaussian Mixture Model. A new optimization protocol was proposed to accurately detect the motile sperms prior to the sperm tracking process. Since the optimization protocol was imposed in the proposed system, the sperm tracking and velocity estimation processes are improved. The proposed method attained the highest average accuracy, sensitivity, and specificity of 92.3%, 96.3%, and 72.4%, respectively, when tested on 10 different samples. Our proposed method depicted better sperm detection quality when qualitatively observed as compared to other state-of-the-art techniques.

Matched MeSH terms: Sperm Motility/physiology*
Sperm parameters quality and reproductive effects of methanolic extract of Alchornea cordifolia leaves on senescent male rats

Ngaha Njila MI, Massoma Lembè D, Koloko BL, Yong Meng G, Ebrahimi M, Awad EA, et al.

Andrologia, 2019 Oct;51(9):e13359.
PMID: 31353623 DOI: 10.1111/and.13359

The effect of the methanolic extract of Alchornea cordifolia leaves on the fertility of senescent male rats was assessed in this study. 40 rats received daily distilled water, testosterone, 200 and 400 mg/kg of extract of Alchornea cordifolia. The reproductive organs weight, the gonadotropins, testosterone and cholesterol level, the sperm parameters, histology of the testes and epididymis were assessed. The weight of testes and prostate (400 mg/kg) significantly increased (p sperm count and morphology significantly increased at both doses of 200 mg/kg (p sperm motion (PROG, VAP, VSL, VCL) (p

Matched MeSH terms: Sperm Motility/physiology
Fulltext Down-regulation of steroidogenesis-related genes and its accompanying fertility decline in streptozotocin-induced diabetic male rats: ameliorative effect of metformin

Nna VU, Bakar ABA, Ahmad A, Mohamed M

Andrology, 2019 01;7(1):110-123.
PMID: 30515996 DOI: 10.1111/andr.12567

BACKGROUND: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged.
OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.
MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.
RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.
DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.

Matched MeSH terms: Sperm Motility/physiology