IGF2 and IGF1R mRNAs Are Detectable in Human Spermatozoa

Rossella Cannarella,Rosita A. Condorelli,Sandro La Vignera,Catia Bellucci,Giovanni Luca,Riccardo Calafiore,Aldo E. Calogero 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.4

Purpose: Oligozoospermia is highly prevalent worldwide. Studies have reported a lower methylation rate in the H19 differentially methylated region at the sperm level in oligozoospermic patients than in controls. IGF2/H19 are the best-known pair of imprinted genes. However, no studies have yet evaluated whether they are transcribed in human sperm. To assess whether IGF2 and IGF1R mRNAs are present in human sperm and if their levels are correlated with sperm concentration and total sperm count. Materials and Methods: Sperm samples (n=22) underwent reverse-transcription quantitative polymerase chain reaction using specific primers to detect IGF2 and IGF1R mRNA levels. They were then correlated with patients’ conventional sperm parameters using the Spearman (τ) and Kendall (ρ) rank correlation coefficients. Results: Statistically significant positive correlations were found between IGF2 mRNA levels and sperm concentration (τ= 0.403, p<0.01; ρ=0.587, p<0.005) and total sperm count (τ=0.347, p<0.024; ρ=0.509, p<0.015). IGF1R mRNA levels were positively correlated with sperm concentration (τ=0.595, p<0.001; ρ=0.774, p<0.001) and total sperm count (τ=0.547, p< 0.001; ρ=0.701, p<0.001). Apart from IGF1R mRNA and sperm morphology (τ=0.325, p<0.05; ρ=0.461, p<0.05), no additional correlations were found between the levels of these transcripts and other conventional sperm parameters. Conclusions: IGF2 and IGF1R mRNAs were found to be present in human spermatozoa and their transcription levels were positively correlated with sperm concentration and total sperm count. Spermatozoa are the only source of IGF2 mRNA since IGF2 is a paternally-inherited gene. Further studies are needed to evaluate its role in human fertilization.

Combined Effects of the FSHR 2039 A/G and FSHR -29 G/A Polymorphisms on Male Reproductive Parameters

Cannarella Rossella,Musso Nicolò,Condorelli Rosita A.,Musmeci Marco,Stefani Stefania,La Vignera Sandro,Calogero Aldo E. 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.3

Purpose: The aim of this study was to evaluate the combined effect of FSHR 2039 A/G and FSHR -29 G/A single nucleotide polymorphisms (SNPs) on the male reproductive function in a cohort of Sicilian men. Materials and Methods: One-hundred thirty Sicilian men were enrolled and underwent blood withdrawal for hormone measurement and FSHR 2039 A/G and FSHR -29 G/A SNP genotyping, testicular volume evaluation by ultrasound scan, and semen analysis. A meta-analysis of the FSHR -29 G/A SNP, evaluated in a previous study of the Sicilian population was done. Results: No genotype of the FSHR 2039 A/G SNP correlated with serum follicle-stimulating hormone (FSH) levels, testicular volume, sperm concentration, and total sperm count. In contrast, normozoospermic men with FSHR -29 GG and FSHR -29 GA genotypes had significantly lower sperm concentrations compared to men with the FSHR -29 AA genotype. The other sperm parameters did not show any significant difference. The meta-analysis showed no significant difference in serum FSH levels, testicular volume, sperm concentration, and total sperm count between FSHR -29 GG and FSHR -29 AA in Sicilian men. No difference was found even when the two SNPs were evaluated in combination. However, this combination was present, as expected, only in a low proportion (3.8%) of the men studied. Conclusions: The SNPs FSHR 2039 A/G and FSHR -29 G/A in combination did not seem to have any effect on male reproductive function in a cohort of Sicilian men. The effect of these SNPs has only been studied in granulosa cells so far. Further studies on their role in Sertoli cells are needed.

Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Agarwal Ashok,Cannarella Rossella,Saleh Ramadan,Harraz Ahmed M.,Kandil Hussein,Salvio Gianmaria,Boitrelle Florence,Kuroda Shinnosuke,Farkouh Ala’a,Rambhatla Amarnath,Zini Armand,Colpi Giovanni,Gül Mur 대한남성과학회 2023 The World Journal of Men's Health Vol.41 No.1

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to in-vestigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Sec-ondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guide-lines. Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated con-trols, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques

Filippo Giacone,Rossella Cannarella,Laura M. Mongioì,Angela Alamo,Rosita A. Condorelli,Aldo E. Calogero,Sandro La Vignera 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.2

During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic inves-tigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

The Global Andrology Forum (GAF): A World-Wide, Innovative, Online Initiative to Bridge the Gaps in Research and Clinical Practice of Male Infertility and Sexual Health

Agarwal Ashok,Saleh Ramadan,Boitrelle Florence,Cannarella Rossella,Hamoda Taha Abo-Almagd Abdel-Meguid,Durairajanayagam Damayanthi,Durairajanayagam Damayanthi,Shah Rupin 대한남성과학회 2022 The World Journal of Men's Health Vol.40 No.4

Thyroid Prostate Axis. Does It Really Exist?

Sandro La Vignera,Rosita A. Condorelli,Rossella Cannarella,Aldo E. Calogero 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.3

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Globozoospermia: A Case Report and Systematic Review of Literature

Crafa Andrea,Condorelli Rosita Angela,Vignera Sandro La,Calogero Aldo Eugenio,Cannarella Rossella 대한남성과학회 2023 The World Journal of Men's Health Vol.41 No.1

Purpose: Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize the oocyte. In this article, we present the clinical case of a young globo-zoospermic patient with a new, not yet described mutation of the DPY19L2 gene. We also performed a systematic review of the literature on gene mutations, the outcome of assisted reproductive techniques, and the risk of transmission of abnormali-ties to the offspring in patients with globozoospermia and made recommendations to offer a more appropriate clinical man-agement of these patients. Materials and Methods: We performed a systematic search in the PubMed, Google Scholar, and Scopus databases from their inception to December 2021. The search strategy included the combination of the following Medical Subjects Headings (MeSH) terms and keywords: “globozoospermia”, “round-headed spermatozoa”, “round head spermatozoa”, “intracytoplas-mic sperm injection”, “ICSI”, “offspring”, “child health”, “assisted reproductive technique outcome”. All the eligible studies were selected following the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model. The quality of included studies was assessed by applying the “Cambridge Quality Checklists”. Results: The main genes involved in the pathogenesis of globozoospermia are DPY19L2, SPATA16, PICK1, GGN, SPACA1, ZPBP, CCDC62, and CCNB3 genes. Other genes could also play a role. These include C2CD6, C7orf61, CCIN, DNH17, DNH6, PIWIL4, and CHPT1. Globozoospermic patients should undergo ART to achieve fertility. In particular, intracytoplas-mic sperm injection with assisted oocyte activation or intracytoplasmic morphologically-selected sperm injection appears to be associated with a higher success rate. Patients with globozoospermia should also be evaluated for the high rate of sperm aneuploidy which appears to influence the success rate of ART but does not appear to be associated with an increased risk of transmission of genetic abnormalities to offspring. Conclusions: This systematic review summarizes the evidence on the gene panel to be evaluated, ICSI outcomes, and the health of the offspring in patients with globozoospermia. Evidence-based recommendations on the management of patients with globozoospermia are provided.

Coenzyme Q10, oxidative stress, and male infertility: A review

Ahmed T. Alahmar,Aldo E. Calogero,Rajender Singh,Rossella Cannarella,Pallav Sengupta,Sulagna Dutta 대한생식의학회 2021 Clinical and Experimental Reproductive Medicine Vol.48 No.2

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.