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Biology
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Pathophysiology of Testis
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Pathophysiology of Testis

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Physiology".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 5399

Special Issue Editors

Dr. María Susana Theas

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Guest Editor
Laboratorio de Regulación de la Espermatogénesis en el Testículo Normal y Patológico, Instituto de Investigaciones Biomédicas (INBIOMED), CONICET-Universidad de Buenos Aires, Ciudad de Buenos Aires C1421ABG, Argentina
Interests: spermatogenesis; germ cells; sertoli cells; sperm; inflammation; immune privilege; nanoplatforms; cell therapy; molecular biology
Dr. Mónica Beatriz Frungieri

E-Mail Website
Guest Editor
Laboratorio de Neuro-Inmuno-Endocrinología Testicular, Instituto de Biología y Medicina Experimental (IBYME), Fundación IBYME, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad de Buenos Aires C1428ADM, Argentina
Interests: testis; male infertility; inflammation; aging; oxidative stress; melatonin; prostaglandins
Dr. María Noel Galardo

E-Mail Website
Guest Editor
Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires C1425EFD, Argentina
Interests: sertoli cells; germ cells; testis; proliferation; cell metabolism; metabolomics; cell biology; molecular biology

Special Issue Information

Dear Colleagues,

The male gonad has both endocrine and reproductive functions. Testicular development and spermatogenesis are under multiple levels of regulation. A complex network of intercellular communication exists between germ cells, Sertoli cells, peritubular myoid cells, Leydig cells, endothelial cells, and macrophages, which is regulated either by direct cell-to-cell contacts, cell-secreted factors—acting in a paracrine, autocrine or intracrine manner—the intercellular transfer of extracellular vesicles, and the phase-specific expression of microRNAs.

Disturbance at any level might alter steroidogenesis, cell energetic metabolism, cell proliferation, and/or sperm production and lead to infertility or subfertility.

This Special Issue aims to explore the molecular and cellular events that govern normal testicular development, testicular cell proliferation, the maintenance of energy balance and ageing, as well as testicular pathology of an immunological, inflammatory, genetic/epigenetic, or unknown etiology. Multi-omic approaches, including single-cell RNA sequencing analysis, metabolomics, and proteomics, contribute to a better understanding of testicular pathophysiology.

Male infertility due to testicular failure has traditionally been regarded as an unchangeable condition due to the lack of effective pharmacological therapies. We encourage research into approaches for the diagnosis and treatment of testicular pathology, which will improve the ability to employ evidence-based medicine in the treatment of 'idiopathic' male infertility.

Dr. María Susana Theas
Dr. Mónica Beatriz Frungieri
Dr. María Noel Galardo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • testis
  • infertility
  • aging
  • inflammation
  • spermatogenesis
  • steroidogenesis
  • energy balance

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Published Papers (2 papers)

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Research

20 pages, 8454 KB  
Article
Effects of Preventive Exposure to High Doses of Alpha-Lipoic Acid (ALA) on Testicular and Sperm Alterations Caused by Scrotal Heat Shock in Mice
by Luciano Cardoso Santos, Maíra Guimarães Kersul, William Morais Machado, Jeane Martinha dos Anjos Cordeiro, Bianca Reis Santos, Cibele Luz Oliveira, Cleisla Souza Oliveira, Larissa Rodrigues Santana, Juneo Freitas Silva and Paola Pereira das Neves Snoeck
Biology 2025, 14(12), 1708; https://doi.org/10.3390/biology14121708 - 30 Nov 2025
Viewed by 1166
Abstract
Alpha-lipoic acid (ALA) is well-known for its antioxidant and anti-inflammatory functions in various disease models. Here, we tested whether pre-exposure to ALA can protect the testes from cellular damage caused by scrotal heat shock (HS) in mice. Methods: Thirty-six Swiss albino mice were [...] Read more.
Alpha-lipoic acid (ALA) is well-known for its antioxidant and anti-inflammatory functions in various disease models. Here, we tested whether pre-exposure to ALA can protect the testes from cellular damage caused by scrotal heat shock (HS) in mice. Methods: Thirty-six Swiss albino mice were divided into control (CTRL, n = 6), HS (n = 10), and two ALA dose (HS + ALA 200 mg/kg, n = 10; and HS + ALA 400 mg/kg, n = 10) groups. ALA supplementation was administered orally for 30 days. Subsequently, the animals, except the controls, were subjected to an HS water bath at 43 °C for 20 min. Two days later, they were euthanized, and biometric data from gonads and accessory sexual glands, testicular samples for histomorphometric and immunohistochemical analyses, and sperm from the epididymis cauda were obtained for evaluation. Results: Animals submitted to HS had a lower body weight, decreased relative mass of testes and prostate, reduced seminiferous epithelium height and tubular diameter, and increased degeneration in seminiferous tubules. Additionally, sperm analysis showed a reduced linear progressive velocity (VSL) and straightness (STR), increased midpiece defects, and fewer sperm with functional membranes. Immunohistochemical evaluation revealed a reduced superoxide dismutase (SOD1) staining intensity in the testes. Preventive exposure to ALA at 200 mg/kg did not normalize the relative testicular mass, but it reduced the number of giant cells, decreased midpiece defects, normalized the number of sperm with functional membranes, and partially preserved SOD1 expression. Although animals treated with ALA 400 mg/kg showed an improvement in relative testicular mass, this dose was less efficient in other parameters. Conclusions: This study showed that while 30 days of oral ingestion of ALA before the induction of acute degenerative injury did not fully protect male mouse gonads at the tissue level, some parameters related to testicular function and sperm quality showed a partial improvement. Full article
(This article belongs to the Special Issue Pathophysiology of Testis)
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22 pages, 5732 KB  
Article
Impaired Spermatogenesis in Infertile Patients with Orchitis and Experimental Autoimmune Orchitis in Rats
by María Sofía Amarilla, Leilane Glienke, Thaisy Munduruca Pires, Cristian Marcelo Sobarzo, Hernán Gustavo Oxilia, María Florencia Fulco, Marcelo Rodríguez Peña, María Belén Maio, Denisse Ferrer Viñals, Livia Lustig, Patricia Verónica Jacobo and María Susana Theas
Biology 2024, 13(4), 278; https://doi.org/10.3390/biology13040278 - 19 Apr 2024
Cited by 2 | Viewed by 3370
Abstract
Experimental autoimmune orchitis (EAO) is a well-established rodent model of organ-specific autoimmunity associated with infertility in which the testis immunohistopathology has been extensively studied. In contrast, analysis of testis biopsies from infertile patients associated with inflammation has been more limited. In this work, [...] Read more.
Experimental autoimmune orchitis (EAO) is a well-established rodent model of organ-specific autoimmunity associated with infertility in which the testis immunohistopathology has been extensively studied. In contrast, analysis of testis biopsies from infertile patients associated with inflammation has been more limited. In this work, testicular biopsies from patients with idiopathic non-obstructive azoospermia diagnosed with hypospermatogenesis (HypoSp) [mild: n = 9, and severe: n = 11], with obstructive azoospermia and complete Sp (spermatogenesis) (control group, C, n = 9), and from Sertoli cell-only syndrome (SCOS, n = 9) were analyzed for the presence of immune cells, spermatogonia and Sertoli cell (SCs) alterations, and reproductive hormones levels. These parameters were compared with those obtained in rats with EAO. The presence of increased CD45+ cells in the seminiferous tubules (STs) wall and lumen in severe HypoSp is associated with increased numbers of apoptotic meiotic germ cells and decreased populations of undifferentiated and differentiated spermatogonia. The SCs showed an immature profile with the highest expression of AMH in patients with SCOS and severe HypoSp. In SCOS patients, the amount of SCs/ST and Ki67+ SCs/ST increased and correlated with high serum FSH levels and CD45+ cells. In the severe phase of EAO, immune cell infiltration and apoptosis of meiotic germ cells increased and the number of undifferentiated and differentiated spermatogonia was lowest, as previously reported. Here, we found that orchitis leads to reduced sperm number, viability, and motility. SCs were mature (AMH-) but increased in number, with Ki67+ observed in severely damaged STs and associated with the highest levels of FSH and inflammatory cells. Our findings demonstrate that in a scenario where a chronic inflammatory process is underway, FSH levels, immune cell infiltration, and immature phenotypes of SCs are associated with severe changes in spermatogenesis, leading to azoospermia. Furthermore, AMH and Ki67 expression in SCs is a distinctive marker of severe alterations of STs in human orchitis. Full article
(This article belongs to the Special Issue Pathophysiology of Testis)
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