Male Reproduction: Regulation, Differentiation and Epigenetics

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Epigenomics".

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 42074

Special Issue Editors


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Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate, Università degli Studi della Campania ‘Luigi Vanvitelli’, Via Santa Maria di Costantinopoli, 16-80138 Napoli, Italy
Interests: reproduction; spermatogenesis; reproductive toxicology; apoptosis; testicular cytoskeleton; gene expression; fertility
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Guest Editor
Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate, Università degli Studi della Campania ‘Luigi Vanvitelli’, Via Santa Maria di Costantinopoli, 16-80138 Napoli, Italy
Interests: reproduction; spermatogenesis; reproductive toxicology; apoptosis; testicular cytoskeleton; blood-testis barrier; fertility
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infertility is a global problem affecting 15%–20% of couples. This condition, equally distributed between males and females, can have several causes, including genetic or epigenetic defects, hypogonadism, as well as environmental and pathological issues. In particular, good-quality spermatozoa with normal morphology and motility are essential for male fertility. Sperm production occurs in the testis and involves the gradual differentiation of germ cells, which changes their size, structural organization, and composition into mature spermatozoa within the extensive seminiferous epithelium. The whole process is harmonized not only by a cell type- and stage-specific induction or repression of the expression of specific genes, but it is also regulated by gonadotropins, steroid hormones, and a complex network of autocrine and paracrine factors. All of the phases leading to the production of mature spermatozoa (spermatogenesis, spermiohistogenesis, and their hormonal control) can be affected by environmental pollutants such as endocrine disruptors, drugs, and micro- and nanoplastics. It must be highlighted that all these factors may contribute not only to affect the sperm quality, but also to produce epigenetic changes that are hereditable and may influence the development and health of offspring. This Special Issue, in addition to expanding the current knowledge on this topic, may be a useful guide for the researchers interested in the field of male infertility.

New research, in vitro and/or in vivo studies in vertebrates, as well as review and clinical studies are all welcome for consideration.

Prof. Sergio Minucci
Dr. Massimo Venditti
Guest Editors

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Keywords

  • Male fertility
  • HPG axis
  • Spermatogenesis
  • Steroidogenesis
  • Blood–testis barrier
  • Endocrine Disrupters
  • Epigenetics
  • Gonadotoxicity
  • Environmental factors
  • Male germ cell development
  • Male germ cell differentiation

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Published Papers (8 papers)

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Editorial

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3 pages, 182 KiB  
Editorial
Male Reproduction: Regulation, Differentiation and Epigenetics
by Massimo Venditti and Sergio Minucci
Genes 2022, 13(6), 1001; https://doi.org/10.3390/genes13061001 - 2 Jun 2022
Viewed by 1768
Abstract
The production of good-quality spermatozoa (SPZ) is one of the most intricate and far from being completely understood developmental processes during postnatal life [...] Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)

Research

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15 pages, 6642 KiB  
Article
Differential Expression of Kisspeptin System and Kisspeptin Receptor Trafficking during Spermatozoa Transit in the Epididymis
by Elena Mele, Raffaella D’Auria, Marika Scafuro, Marianna Marino, Silvia Fasano, Andrea Viggiano, Riccardo Pierantoni, Antonietta Santoro and Rosaria Meccariello
Genes 2022, 13(2), 295; https://doi.org/10.3390/genes13020295 - 2 Feb 2022
Cited by 14 | Viewed by 2817
Abstract
The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to [...] Read more.
The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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16 pages, 3812 KiB  
Article
Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis
by Massimo Venditti, Mariem Ben Rhouma, Maria Zelinda Romano, Imed Messaoudi, Russel J. Reiter and Sergio Minucci
Genes 2021, 12(7), 1016; https://doi.org/10.3390/genes12071016 - 30 Jun 2021
Cited by 30 | Viewed by 4226
Abstract
Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues, including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells and provoked testicular injury, as documented by biomolecular [...] Read more.
Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues, including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells and provoked testicular injury, as documented by biomolecular and histological alterations, i.e., CAT and SOD activity, the protein level of steroidogenic enzymes (StAR and 3β-HSD), and morphometric parameters. Additionally, it further documents the melatonin (MLT) coadministration produces affects in mitigating Cd-induced toxicity on adult rat testis, as demonstrated by the reduction of oxidative stress and apoptosis, with reversal of the observed histological changes; moreover, a role of MLT in partially restoring steroidogenic enzymes expression was evidenced. Importantly, the cytoarchitecture of testicular cells was perturbed by Cd exposure, as highlighted by impairment of the expression and localization of two cytoskeleton-associated proteins DAAM1 and PREP, which are involved in the germ cells’ differentiation into spermatozoa, altering the normal spermatogenesis. Here, for the first time, we found that the co-treatment with MLT attenuated the Cd-induced toxicity on the testicular DAAM1 and PREP expression. The combined findings provide additional clues about a protective effect of MLT against Cd-induced testicular toxicity by acting on DAAM1 and PREP expression, encouraging further studies to prove its effectiveness in human health. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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10 pages, 1434 KiB  
Article
Evolution of Reproductive Life History in Mammals and the Associated Change of Functional Constraints
by Jiaqi Wu, Takahiro Yonezawa and Hirohisa Kishino
Genes 2021, 12(5), 740; https://doi.org/10.3390/genes12050740 - 14 May 2021
Cited by 10 | Viewed by 3818
Abstract
Phylogenetic trees based on multiple genomic loci enable us to estimate the evolution of functional constraints that operate on genes based on lineage-specific fluctuation of the evolutionary rate at particular gene loci, “gene–branch interactions”. Using this information as predictors, our previous work inferred [...] Read more.
Phylogenetic trees based on multiple genomic loci enable us to estimate the evolution of functional constraints that operate on genes based on lineage-specific fluctuation of the evolutionary rate at particular gene loci, “gene–branch interactions”. Using this information as predictors, our previous work inferred that the common ancestor of placental mammals was nocturnal, insectivorous, solitary, and bred seasonally. Here, we added seven new continuous traits including lifespan, bodyweight, and five reproduction-related traits and inferred the coevolution network of 14 core life history traits for 89 mammals. In this network, bodyweight and lifespan are not directly connected to each other; instead, their correlation is due to both of them coevolving with gestation period. Diurnal mammals are more likely to be monogamous than nocturnal mammals, while arboreal mammals tend to have a smaller litter size than terrestrial mammals. Coevolution between diet and the seasonal breeding behavior test shows that year-round breeding preceded the dietary change to omnivory, while seasonal breeding preceded the dietary change to carnivory. We also discuss the evolution of reproductive strategy of mammals. Genes selected as predictors were identified as well; for example, genes function as tumor suppressor were selected as predictors of weaning age. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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Review

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11 pages, 282 KiB  
Review
Fertility of Cryptorchid Testis—An Unsolved Mistery
by Carmen Iulia Ciongradi, Ioan Sârbu, Codruța Olimpiada Iliescu Halițchi, Diana Benchia and Klara Sârbu
Genes 2021, 12(12), 1894; https://doi.org/10.3390/genes12121894 - 26 Nov 2021
Cited by 14 | Viewed by 10866
Abstract
Cryptorchidism (undescended testis) is one of the most common diagnoses in the pediatric urologist office. Even in the modern era, there still are a lot of debates regarding the optimal time for surgery related to the expected results in relation with the testicular [...] Read more.
Cryptorchidism (undescended testis) is one of the most common diagnoses in the pediatric urologist office. Even in the modern era, there still are a lot of debates regarding the optimal time for surgery related to the expected results in relation with the testicular function, including fertility. The review below intends to clarify issues regarding the impact of cryptorchidism on testicular histology and function, semen analysis, the relation between hormonal and surgical treatment, future fertility, and paternity rate. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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16 pages, 1411 KiB  
Review
Prospects in Connecting Genetic Variation to Variation in Fertility in Male Bees
by Garett P. Slater, Nicholas M. A. Smith and Brock A. Harpur
Genes 2021, 12(8), 1251; https://doi.org/10.3390/genes12081251 - 16 Aug 2021
Cited by 7 | Viewed by 8850
Abstract
Bees are economically and ecologically important pollinating species. Managed and native bee species face increasing pressures from human-created stressors such as habitat loss, pesticide use, and introduced pathogens. There has been increasing attention towards how each of these factors impacts fertility, especially sperm [...] Read more.
Bees are economically and ecologically important pollinating species. Managed and native bee species face increasing pressures from human-created stressors such as habitat loss, pesticide use, and introduced pathogens. There has been increasing attention towards how each of these factors impacts fertility, especially sperm production and maintenance in males. Here, we turn our attention towards another important factor impacting phenotypic variation: genetics. Using honey bees as a model, we explore the current understanding of how genetic variation within and between populations contributes to variation in sperm production, sperm maintenance, and insemination success among males. We conclude with perspectives and future directions in the study of male fertility in honey bees and non-Apis pollinators more broadly, which still remain largely understudied. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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20 pages, 374 KiB  
Review
Pediatric and Adolescent Oncofertility in Male Patients—From Alpha to Omega
by Ovidiu Bîcă, Ioan Sârbu and Carmen Iulia Ciongradi
Genes 2021, 12(5), 701; https://doi.org/10.3390/genes12050701 - 8 May 2021
Cited by 11 | Viewed by 3890
Abstract
This article reviews the latest information about preserving reproductive potential that can offer enhanced prospects for future conception in the pediatric male population with cancer, whose fertility is threatened because of the gonadotoxic effects of chemotherapy and radiation. An estimated 400,000 children and [...] Read more.
This article reviews the latest information about preserving reproductive potential that can offer enhanced prospects for future conception in the pediatric male population with cancer, whose fertility is threatened because of the gonadotoxic effects of chemotherapy and radiation. An estimated 400,000 children and adolescents aged 0–19 years will be diagnosed with cancer each year. Fertility is compromised in one-third of adult male survivors of childhood cancer. We present the latest approaches and techniques for fertility preservation, starting with fertility preservation counselling, a clinical practice guideline used around the world and finishing with recent advances in basic science and translational research. Improving strategies for the maturation of germ cells in vitro combined with new molecular techniques for gene editing could be the next scientific keystone to eradicate genetic diseases such as cancer related mutations in the offspring of cancer survivors. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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16 pages, 1238 KiB  
Review
LINCking the Nuclear Envelope to Sperm Architecture
by Francesco Manfrevola, Florian Guillou, Silvia Fasano, Riccardo Pierantoni and Rosanna Chianese
Genes 2021, 12(5), 658; https://doi.org/10.3390/genes12050658 - 27 Apr 2021
Cited by 15 | Viewed by 4487
Abstract
Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette [...] Read more.
Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility. Full article
(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)
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