Journal of Clinical Medicine

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12 pages, 2239 KiB

Open AccessArticle

Respiratory Mitochondrial Efficiency and DNA Oxidation in Human Sperm after In Vitro Myo-Inositol Treatment

by Laura Governini, Rosetta Ponchia, Paolo Giovanni Artini, Elena Casarosa, Ilaria Marzi, Angela Capaldo, Alice Luddi and Paola Piomboni

J. Clin. Med. 2020, 9(6), 1638; https://doi.org/10.3390/jcm9061638 - 28 May 2020

Cited by 18 | Viewed by 2581

Abstract

Semen samples are known to contain abnormal amounts of reactive oxygen species (ROS) and oxygen free radicals; therefore, the identification of antioxidant molecules able to counteract the oxidative damage caused by ROS is foresight. Indeed, improving semen quality in terms of motility and [...] Read more.

Semen samples are known to contain abnormal amounts of reactive oxygen species (ROS) and oxygen free radicals; therefore, the identification of antioxidant molecules able to counteract the oxidative damage caused by ROS is foresight. Indeed, improving semen quality in terms of motility and reduction in DNA damage, can significantly improve the fertilization potential of sperm in vitro. To this regard, myo-inositol, based on its antioxidant properties, has been reported to be effective in improving sperm quality and motility in oligoasthenozoospermic patients undergoing assisted reproduction techniques when used as a dietary supplementation. Moreover, in vitro treatment demonstrated a direct relationship between myo-inositol, mitochondrial membrane potential and sperm motility. This experimental study aimed to evaluate the effects of myo-inositol (Andrositol-lab) in vitro treatment on sperm motility, capacitation, mitochondrial oxidative phosphorylation and DNA damage. Our results demonstrate that myo-inositol induces a significant increase in sperm motility and in oxygen consumption, the main index of oxidative phosphorylation efficiency and ATP production, both in basal and in in vitro capacitated samples. Moreover, we provide evidence for a significant protective role of myo-inositol against oxidative damage to DNA, thus supporting the in vitro use of myo-inositol in assisted reproductive techniques. Even if further studies are needed to clarify the mechanisms underlying the antioxidant properties of myo-inositol, the present findings significantly extend our knowledge on human male fertility and pave the way to the definition of evidence-based guidelines, aiming to improve the in vitro procedure currently used in ART laboratory for sperm selection. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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7 pages, 530 KiB

Open AccessCommunication

D-Chiro-Inositol Improves Sperm Mitochondrial Membrane Potential: In Vitro Evidence

by Rosita A. Condorelli, Federica Barbagallo, Aldo E. Calogero, Rossella Cannarella, Andrea Crafa and Sandro La Vignera

J. Clin. Med. 2020, 9(5), 1373; https://doi.org/10.3390/jcm9051373 - 07 May 2020

Cited by 13 | Viewed by 2926

Abstract

The use of inositols in endocrinological clinical practice is increasingly widespread. Most of the existing evidence concerns myoinositol (MYO), the most abundant form in nature, especially in women with polycystic ovarian syndrome. We have previously shown that MYO increases sperm motility in patients [...] Read more.

The use of inositols in endocrinological clinical practice is increasingly widespread. Most of the existing evidence concerns myoinositol (MYO), the most abundant form in nature, especially in women with polycystic ovarian syndrome. We have previously shown that MYO increases sperm motility in patients with asthenozoospermia by the increase of sperm mitochondrial membrane potential (MMP), a biofunctional sperm parameter closely associated to sperm motility. The aim of this study was to evaluate the effects of D-chiro-inositol (DCI), another biologically active isoform of inositols, on sperm MMP, as data on this matter has never been released so far. To accomplish this, semen samples from 15 patients with asthenozoospermia and 15 healthy normozoospermic men were incubated with increasing concentrations of DCI (0, 75, and 750 µg/mL) or phosphate buffer saline for 30 min. Incubation with DCI significantly improved sperm MMP at lower concentrations, and with shorter incubation length than those used in our similar MYO studies. In conclusion, these findings indicate that DCI positively impacts on sperm mitochondrial function in vitro. Studies aimed at assessing the role of DCI in the treatment of asthenozoospermia in-vivo are warranted. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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8 pages, 238 KiB

Open AccessArticle

Anthropometric Variables as Predictors of Semen Parameters and Fertility Outcomes after Varicocelectomy

by Ramy Abou Ghayda, Robert Zakhia El-Doueihi, Jun Young Lee, Muhammad Bulbul, Nassib Abou Heidar, Jad Bulbul, Samer Asmar, Sung Hwi Hong, Jae Won Yang, Andreas Kronbichler and Jae Il Shin

J. Clin. Med. 2020, 9(4), 1160; https://doi.org/10.3390/jcm9041160 - 18 Apr 2020

Cited by 6 | Viewed by 1921

Abstract

Varicocele is the most common correctable male infertility factor and varicocelectomy has been a mainstay in the management of infertility. However, the role of varicocelectomy as a treatment option has been controversial, and the scientific debate around it is still ongoing. Our study [...] Read more.

Varicocele is the most common correctable male infertility factor and varicocelectomy has been a mainstay in the management of infertility. However, the role of varicocelectomy as a treatment option has been controversial, and the scientific debate around it is still ongoing. Our study aimed to explore the role of anthropometric variables of infertile patients and their relation to sperm parameters following varicocelectomy. The outcome of 124 infertile patients who underwent open sub-inguinal varicocelectomy by a single surgeon over the last ten years was studied. Post varicocelectomy, four semen parameters (volume, total count, motility, and morphology) were analyzed and adjusted according to anthropometric variables including age, varicocele grade, and body mass index (BMI) of patients. Total count and motility were significantly improved after surgery. Varicocelectomy improved semen parameters, notably the count and the motility, especially in younger patients, lower grades of varicocele patients, and low BMI patients. In addition, BMI was positively correlated with volume in pre-varicocelectomy and post-varicocelectomy. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

10 pages, 2038 KiB

Open AccessArticle

The Tissue-Sparing Effect of Spatially Fractionated X-rays for Maintaining Spermatogenesis: A Radiobiological Approach for the Preservation of Male Fertility after Radiotherapy

by Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Ritsuko Watanabe, Takehiko Ogawa, Akinari Yokoya and Kevin M. Prise

J. Clin. Med. 2020, 9(4), 1089; https://doi.org/10.3390/jcm9041089 - 11 Apr 2020

Cited by 6 | Viewed by 2752

Abstract

Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially [...] Read more.

Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially fractionated radiation. In the present study, we used an ex vivo mouse testicular tissue culture model and a conventional X-ray irradiation device to evaluate the tissue-sparing effect (TSE) of spatially fractionated X-rays for the protection of male fertility from radiotherapy-related adverse effects. We revealed a significant TSE for maintaining spermatogenesis in the ex vivo testes model following spatially fractionated X-ray irradiation. Moreover, we experimentally propose a possible mechanism by which the migration of spermatogonial cells, from the non-irradiated areas to the irradiated ones, in irradiated testicular tissue, is essential for the TSE and maintaining spermatogenesis. Therefore, our findings demonstrate that the control of TSE following spatially fractionated X-rays in the testes has a considerable potential for clinical application. Interdisciplinary research will be essential for further expanding the applicability of this method as an approach for the preservation of male fertility during or after radiotherapy. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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15 pages, 3188 KiB

Open AccessArticle

The Glucocorticoid Receptor NR3C1 in Testicular Peritubular Cells is Developmentally Regulated and Linked to the Smooth Muscle-Like Cellular Phenotype

by Harald Welter, Carola Herrmann, Nils Dellweg, Annika Missel, Christiane Thanisch, Henryk F. Urbanski, Frank-Michael Köhn, J. Ullrich Schwarzer, Annette Müller-Taubenberger and Artur Mayerhofer

J. Clin. Med. 2020, 9(4), 961; https://doi.org/10.3390/jcm9040961 - 31 Mar 2020

Cited by 15 | Viewed by 3175

Abstract

Whether glucocorticoids (GC) can directly affect human testicular functions is not well understood. A predominant site of GC receptor (GR; NR3C1) expression in the adult testis are peritubular smooth muscle-like cells, which express smooth muscle actin (ACTA2), contract and thereby are involved [...] Read more.

Whether glucocorticoids (GC) can directly affect human testicular functions is not well understood. A predominant site of GC receptor (GR; NR3C1) expression in the adult testis are peritubular smooth muscle-like cells, which express smooth muscle actin (ACTA2), contract and thereby are involved in sperm transport. In contrast to the adult, neither GR nor ACTA2, or elastin (ELN) were detected in the peritubular compartment before puberty in non-human primate testes. In isolated human testicular peritubular cells (HTPCs), activation of GR by dexamethasone (Dex) caused the translocation of GR to the nucleus and stimulated expression of ACTA2 and ELN, without affecting the expression of collagens. Cytoskeletal ACTA2-rearrangements were observed and were associated with an increased ability to contract. Our results indicate post-pubertal testicular roles of GC in the maintenance of the contractile, smooth muscle-like phenotype of peritubular cells. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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19 pages, 11621 KiB

Open AccessArticle

Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

by Marsida Hutka, Lee B. Smith, Ellen Goossens, W. Hamish B. Wallace, Jan-Bernd Stukenborg and Rod T. Mitchell

J. Clin. Med. 2020, 9(1), 266; https://doi.org/10.3390/jcm9010266 - 18 Jan 2020

Cited by 11 | Viewed by 4747

Abstract

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. [...] Read more.

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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17 pages, 1759 KiB

Open AccessArticle

Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm

by Laura Governini, Bianca Semplici, Valentina Pavone, Laura Crifasi, Camilla Marrocco, Vincenzo De Leo, Elisabeth Arlt, Thomas Gudermann, Ingrid Boekhoff, Alice Luddi and Paola Piomboni

J. Clin. Med. 2020, 9(1), 264; https://doi.org/10.3390/jcm9010264 - 18 Jan 2020

Cited by 33 | Viewed by 5720

Abstract

Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, [...] Read more.

Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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17 pages, 2954 KiB

Open AccessArticle

Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

by Joana M. D. Portela, Laura Heckmann, Joachim Wistuba, Andrea Sansone, Ans M. M. van Pelt, Sabine Kliesch, Stefan Schlatt and Nina Neuhaus

J. Clin. Med. 2020, 9(1), 224; https://doi.org/10.3390/jcm9010224 - 14 Jan 2020

Cited by 6 | Viewed by 3030

Abstract

Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and [...] Read more.

Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients’, establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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Review

Jump to: Research

27 pages, 2331 KiB

Open AccessReview

Follicle-Stimulating Hormone (FSH) Action on Spermatogenesis: A Focus on Physiological and Therapeutic Roles

by Daniele Santi, Pascale Crépieux, Eric Reiter, Giorgia Spaggiari, Giulia Brigante, Livio Casarini, Vincenzo Rochira and Manuela Simoni

J. Clin. Med. 2020, 9(4), 1014; https://doi.org/10.3390/jcm9041014 - 03 Apr 2020

Cited by 58 | Viewed by 13403

Abstract

Background: Human reproduction is regulated by the combined action of the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) on the gonads. Although FSH is largely used in female reproduction, in particular in women attending assisted reproductive techniques to stimulate multi-follicular growth, its [...] Read more.

Background: Human reproduction is regulated by the combined action of the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) on the gonads. Although FSH is largely used in female reproduction, in particular in women attending assisted reproductive techniques to stimulate multi-follicular growth, its efficacy in men with idiopathic infertility is not clearly demonstrated. Indeed, whether FSH administration improves fertility in patients with hypogonadotropic hypogonadism, the therapeutic benefit in men presenting alterations in sperm production despite normal FSH serum levels is still unclear. In the present review, we evaluate the potential pharmacological benefits of FSH administration in clinical practice. Methods: This is a narrative review, describing the FSH physiological role in spermatogenesis and its potential therapeutic action in men. Results: The FSH role on male fertility is reviewed starting from the physiological control of spermatogenesis, throughout its mechanism of action in Sertoli cells, the genetic regulation of its action on spermatogenesis, until the therapeutic options available to improve sperm production. Conclusion: FSH administration in infertile men has potential benefits, although its action should be considered by evaluating its synergic action with testosterone, and well-controlled, powerful trials are required. Prospective studies and new compounds could be developed in the near future. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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43 pages, 2922 KiB

Open AccessReview

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

by Teresa Chioccarelli, Riccardo Pierantoni, Francesco Manfrevola, Veronica Porreca, Silvia Fasano, Rosanna Chianese and Gilda Cobellis

J. Clin. Med. 2020, 9(3), 640; https://doi.org/10.3390/jcm9030640 - 27 Feb 2020

Cited by 36 | Viewed by 6308

Abstract

Spermatozoa (SPZ) are motile cells, characterized by a cargo of epigenetic information including histone post-translational modifications (histone PTMs) and non-coding RNAs. Specific histone PTMs are present in developing germ cells, with a key role in spermatogenic events such as self-renewal and commitment of [...] Read more.

Spermatozoa (SPZ) are motile cells, characterized by a cargo of epigenetic information including histone post-translational modifications (histone PTMs) and non-coding RNAs. Specific histone PTMs are present in developing germ cells, with a key role in spermatogenic events such as self-renewal and commitment of spermatogonia (SPG), meiotic recombination, nuclear condensation in spermatids (SPT). Nuclear condensation is related to chromatin remodeling events and requires a massive histone-to-protamine exchange. After this event a small percentage of chromatin is condensed by histones and SPZ contain nucleoprotamines and a small fraction of nucleohistone chromatin carrying a landascape of histone PTMs. Circular RNAs (circRNAs), a new class of non-coding RNAs, characterized by a nonlinear back-spliced junction, able to play as microRNA (miRNA) sponges, protein scaffolds and translation templates, have been recently characterized in both human and mouse SPZ. Since their abundance in eukaryote tissues, it is challenging to deepen their biological function, especially in the field of reproduction. Here we review the critical role of histone PTMs in male germ cells and the profile of circRNAs in mouse and human SPZ. Furthermore, we discuss their suggested role as novel epigenetic biomarkers to assess sperm quality and improve artificial insemination procedure. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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18 pages, 692 KiB

Open AccessReview

Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

by Francesco Pallotti, Marianna Pelloni, Daniele Gianfrilli, Andrea Lenzi, Francesco Lombardo and Donatella Paoli

J. Clin. Med. 2020, 9(2), 471; https://doi.org/10.3390/jcm9020471 - 08 Feb 2020

Cited by 38 | Viewed by 6611

Abstract

Great attention has been paid in recent years to the harmful effects of various chemicals that interfere with our natural hormone balance, collectively known as endocrine-disrupting chemicals (EDCs) or endocrine disruptors. The effects on the reproductive system of bisphenol A (BPA) and phthalates [...] Read more.

Great attention has been paid in recent years to the harmful effects of various chemicals that interfere with our natural hormone balance, collectively known as endocrine-disrupting chemicals (EDCs) or endocrine disruptors. The effects on the reproductive system of bisphenol A (BPA) and phthalates have received particular attention: while they have a short half-life, they are so widespread that human exposure can be considered as continuous. Evidence is often limited to the animal model, disregarding the likelihood of human exposure to a mixture of contaminants. Data from animal models show that maternal exposure probably has harmful effects on the male fetus, with an increased risk of urogenital developmental abnormalities. After birth, exposure is associated with changes in the hypothalamic-pituitary-testicular axis, hindering the development and function of the male genital pathways through the mediation of inflammatory mechanisms and oxidative stress. The epidemiological and clinical evidence, while generally confirming the association between reproductive abnormalities and some phthalate esters and BPA, is more contradictory, with wildly different findings. The aim of this review is therefore to provide an update of the potential mechanisms of the damage caused by BPA and phthalates to reproductive function and a review of the clinical evidence currently available in the literature. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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12 pages, 414 KiB

Open AccessReview

Evaluation of Sperm Mitochondrial Function: A Key Organelle for Sperm Motility

by Federica Barbagallo, Sandro La Vignera, Rossella Cannarella, Antonio Aversa, Aldo E. Calogero and Rosita A. Condorelli

J. Clin. Med. 2020, 9(2), 363; https://doi.org/10.3390/jcm9020363 - 29 Jan 2020

Cited by 96 | Viewed by 5842

Abstract

Introduction: The role of nutraceuticals in the treatment of male infertility, especially in the “idiopathic form”, remains the subject of significant debate. Many antioxidants improve sperm motility but the exact mechanism by which they act is still unclear. Although several studies have shown [...] Read more.

Introduction: The role of nutraceuticals in the treatment of male infertility, especially in the “idiopathic form”, remains the subject of significant debate. Many antioxidants improve sperm motility but the exact mechanism by which they act is still unclear. Although several studies have shown a correlation between sperm motility and mitochondrial function, the effects of antioxidant therapy on mitochondrial membrane potential (MMP) are poorly studied. The first aim of this review was to evaluate the efficacy of antioxidants on mitochondrial function and, consequently, on sperm motility in male infertile patients. Material and Methods: we performed a systematic search of all randomized controlled and uncontrolled studies available in the literature that reported sperm motility and MMP at baseline and after antioxidant administration in-vivo and in-vitro in patients with idiopathic asthenozoospermia. Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases were used. Results: Unexpectedly, among 353 articles retrieved, only one study met our inclusion criteria and showed a significant effect of myoinositol on both MMP and sperm motility. We then summarized the main knowledge on anatomy and metabolism of sperm mitochondria, techniques allowing to assess sperm mitochondria function and its relationships with low sperm motility. Finally, we paid special attention to the effect of antioxidant/prokinetic molecules for the treatment of asthenozoospermia. Conclusions: This is the first systematic review that has attempted to evaluate the effects of antioxidants on MMP and sperm motility. Although results are not conclusive due to the dearth of studies, the close relationship between mitochondria and sperm motility is clear. The investigation of this correlation could provide valuable information to be exploited in clinical practice for the treatment of male infertility. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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25 pages, 1616 KiB

Open AccessReview

Male Infertility: Shining a Light on Lipids and Lipid-Modulating Enzymes in the Male Germline

by Jessica L.H. Walters, Bart M. Gadella, Jessie M. Sutherland, Brett Nixon and Elizabeth G. Bromfield

J. Clin. Med. 2020, 9(2), 327; https://doi.org/10.3390/jcm9020327 - 23 Jan 2020

Cited by 23 | Viewed by 4572

Abstract

Despite the prevalence of male factor infertility, most cases are defined as idiopathic, thus limiting treatment options and driving increased rates of recourse to assisted reproductive technologies (ARTs). Regrettably, our current armory of ARTs does not constitute therapeutic treatments for male infertility, thus [...] Read more.

Despite the prevalence of male factor infertility, most cases are defined as idiopathic, thus limiting treatment options and driving increased rates of recourse to assisted reproductive technologies (ARTs). Regrettably, our current armory of ARTs does not constitute therapeutic treatments for male infertility, thus highlighting an urgent need for novel intervention strategies. In our attempts to fill this void, we have come to appreciate that the production of pathological levels of oxygen radicals within the male germline are a defining etiology of many idiopathic infertility cases. Indeed, an imbalance of reactive oxygen species can precipitate a cascade of deleterious sequelae, beginning with the peroxidation of membrane lipids and culminating in cellular dysfunction and death. Here, we shine light on the importance of lipid homeostasis, and the impact of lipid stress in the demise of the male germ cell. We also seek to highlight the utility of emerging lipidomic technologies to enhance our understanding of the diverse roles that lipids play in sperm function, and to identify biomarkers capable of tracking infertility in patient cohorts. Such information should improve our fundamental understanding of the mechanistic causes of male infertility and find application in the development of efficacious treatment options. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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27 pages, 742 KiB

Open AccessReview

Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic

by Miriam Cerván-Martín, José A. Castilla, Rogelio J. Palomino-Morales and F. David Carmona

J. Clin. Med. 2020, 9(2), 300; https://doi.org/10.3390/jcm9020300 - 21 Jan 2020

Cited by 46 | Viewed by 5426

Abstract

Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have [...] Read more.

Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, different genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men. However, these alterations only explain around 25% of azoospermic cases, with the remaining patients showing an idiopathic origin. Recent studies clearly suggest that the so-called idiopathic NOA has a complex aetiology with a polygenic inheritance, which may alter the spermatogenic process. Although we are far from a complete understanding of the molecular mechanisms underlying NOA, the use of the new technologies for genetic analysis has enabled a considerable increase in knowledge during the last years. In this review, we will provide a comprehensive and updated overview of the genetic basis of NOA, with a special focus on the possible application of the recent insights in clinical practice. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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11 pages, 974 KiB

Open AccessReview

Tachykinins and Kisspeptins in the Regulation of Human Male Fertility

by Víctor Blasco, Francisco M. Pinto, Cristina González-Ravina, Esther Santamaría-López, Luz Candenas and Manuel Fernández-Sánchez

J. Clin. Med. 2020, 9(1), 113; https://doi.org/10.3390/jcm9010113 - 31 Dec 2019

Cited by 9 | Viewed by 4437

Abstract

Infertility is a global disease affecting one out of six couples of reproductive age in the world, with a male factor involved in half the cases. There is still much to know about the regulation of human male fertility and thus we decided [...] Read more.

Infertility is a global disease affecting one out of six couples of reproductive age in the world, with a male factor involved in half the cases. There is still much to know about the regulation of human male fertility and thus we decided to focus on two peptide families that seem to play a key role in this function: tachykinins and kisspeptins. With this aim, we conducted an exhaustive review in order to describe the role of tachykinins and kisspeptins in human fertility and their possible implications in infertility etiopathogenesis. Many advances have been made to elucidate the roles of these two families in infertility, and multiple animal species have been studied, including humans. All of this knowledge could lead to new advances in male infertility diagnosis and treatment, but further research is needed to clarify all the implications of tachykinins and kisspeptins in fertility. Full article

(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)

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