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Male Reproductive Health and Infertility: A Look towards the Future...
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Male Reproductive Health and Infertility: A Look towards the Future II

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 7119

Special Issue Editors

Dr. Alice Luddi

E-Mail Website
Guest Editor
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
Interests: male infertility; spermatogenesis; female infertility; endometrial receptivity; gene expression
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Paola Piomboni

E-Mail Website
Guest Editor
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
Interests: male infertility; spermatogenesis; female infertility; endometrial receptivity; gene expression
Special Issues, Collections and Topics in MDPI journals
Dr. Rosanna Chianese

E-Mail Website
Guest Editor
Department of Experimental Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy
Interests: male infertility; spermatogenesis; sperm quality; epigenetics; non-coding RNAs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The success of the first edition of this Special Issue encouraged us to launch a second edition. 

The testicular milieu harboring germ cell progression is coordinated by gonadotropins, steroid hormones, and a complex network of autocrine and paracrine factors. The final goal of spermatogenesis is the production of highly specialized cells, the spermatozoa, essential for species continuation. Furthermore, morphological, molecular, and epigenetic quality of sperm cells is a crucial aspect to guarantee successful fertilization and a regular embryo development. Nuclear remodeling during spermatogenesis is also critical for sperm quality, since it influences acrosome biogenesis, flagellum formation, and chromosome distribution.

Paternal health at the time of conception is increasingly considered a key factor affecting offspring health. Meanwhile, paternal lifestyle, including exposure to endocrine disruptors and nutrition, can alter the phenotype of future generations, especially by remodeling the epigenetic blueprint of sperm. Following the substantial decline of sperm quality in recent decades and the strong correlation between male infertility and comorbidities such as oncologic, metabolic, cardiovascular, and autoimmune diseases, the need is clear to adequately study this alarming global health issue.

The purpose of this Special Issue is to provide a global overview of male fertility ranging from the molecular mechanisms driving a normal spermatogenesis to the molecular remodeling of sperm during epididymal transit, with a special focus on cell communication mediated by free or exosome-embedded molecules. This Special Issue focuses on innovative technological strategies, including testicular organ culture systems and emerging pluripotent stem cell technology that are expected to provide in vitro spermatogenesis in the future.

Moreover, this Issue will also cover the molecular, genetic/epigenetic, and endocrine aspects that may provide new, interesting clues in male infertility. Another important aspect will be the identification of new effective biomarkers for an early and reliable diagnosis of male infertility that may make possible the specific pharmacological management of patients.

Dr. Alice Luddi
Prof. Dr. Paola Piomboni
Dr. Rosanna Chianese
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cells 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

  • sperm
  • male infertility
  • spermatogenesis
  • epigenetics
  • fertilization
  • exosomes
  • cell communication
  • oxidative stress
  • biomarkers

Published Papers (5 papers)

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Research

20 pages, 9968 KiB  
Article
Inhibition of miR-143-3p Restores Blood–Testis Barrier Function and Ameliorates Sertoli Cell Senescence
by Ziyan Xiao, Jinlian Liang, Rufei Huang, Derong Chen, Jiaxin Mei, Jingxian Deng, Zhaoyang Wang, Lu Li, Ziyi Li, Huan Xia, Yan Yang and Yadong Huang
Cells 2024, 13(4), 313; https://doi.org/10.3390/cells13040313 - 08 Feb 2024
Viewed by 797
Abstract
Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli [...] Read more.
Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli cell aging is still unclear. In this study, senescent Sertoli cells showed a substantial upregulation of miR-143-3p expression. miR-143-3p was found to limit Sertoli cell proliferation, promote cellular senescence, and cause blood–testis barrier (BTB) dysfunction by targeting ubiquitin-conjugating enzyme E2 E3 (UBE2E3). Additionally, the TGF-β receptor inhibitor SB431542 showed potential in alleviating age-related BTB dysfunction, rescuing testicular atrophy, and reversing the reduction in germ cell numbers by negatively regulating miR-143-3p. These findings clarified the regulatory pathways underlying Sertoli cell senescence and suggested a promising therapeutic approach to restore BTB function, alleviate Sertoli cell senescence, and improve reproductive outcomes for individuals facing fertility challenges. Full article
(This article belongs to the Special Issue Male Reproductive Health and Infertility: A Look towards the Future II)
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12 pages, 1831 KiB  
Article
Exposure to Cumulus Cell Secretome Improves Sperm Function: New Perspectives for Sperm Selection In Vitro
by Francesca Paola Luongo, Silvia Perez Casasus, Alesandro Haxhiu, Fabio Barbarulo, Marta Scarcella, Laura Governini, Paola Piomboni, Catello Scarica and Alice Luddi
Cells 2023, 12(19), 2349; https://doi.org/10.3390/cells12192349 - 25 Sep 2023
Cited by 1 | Viewed by 1209
Abstract
In the literature, there is a well-known correlation between poor semen quality and DNA sperm integrity, which can turn into negative outcomes in terms of embryo development and clinical pregnancy. Sperm selection plays a pivotal role in clinical practice, and the most widely [...] Read more.
In the literature, there is a well-known correlation between poor semen quality and DNA sperm integrity, which can turn into negative outcomes in terms of embryo development and clinical pregnancy. Sperm selection plays a pivotal role in clinical practice, and the most widely used methods are mainly based on sperm motility and morphology. The cumulus oophorus complex (COC) during natural fertilization represents a barrier that spermatozoa must overcome to reach the zona pellucida and fertilize the oocyte. Spermatozoa that can pass through the COC have better structural and metabolic characteristics as well as enhanced acrosome reaction (AR). The present study aimed to evaluate the exposure of sperm to cumulus cell secretome during swim-up treatment (SUC) compared with the routinely used swim-up method (SU). To determine the effectiveness of this method, biological factors critical for the ability of sperm to fertilize an oocyte, including capacitation, AR, tyrosine phosphorylation signature, DNA integrity, and mitochondrial functionality, were assessed. The SUC selection assures recovery of high-quality spermatozoa, with enhanced mitochondrial functionality and motility compared with both SU-selected and unselected (U) sperm. Furthermore, using this modified swim-up procedure, significantly reduced sperm DNA damage (p < 0.05) was detected. In conclusion, the SUC approach is a more physiological and integrated method for sperm selection that deserves further investigation for its translation into clinical practice. Full article
(This article belongs to the Special Issue Male Reproductive Health and Infertility: A Look towards the Future II)
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21 pages, 16903 KiB  
Article
Effects of Growth Factors on In Vitro Culture of Neonatal Piglet Testicular Tissue Fragments
by Fahar Ibtisham, Tat-Chuan Cham, Mohammad Amin Fayaz and Ali Honaramooz
Cells 2023, 12(18), 2234; https://doi.org/10.3390/cells12182234 - 08 Sep 2023
Viewed by 1194
Abstract
In vitro spermatogenesis (IVS) has important applications including fertility preservation of prepubertal cancer patients; however, thus far, IVS has only been achieved using mouse models. To study the effects of growth factors on the maintenance of testicular tissue integrity, germ cell numbers, and [...] Read more.
In vitro spermatogenesis (IVS) has important applications including fertility preservation of prepubertal cancer patients; however, thus far, IVS has only been achieved using mouse models. To study the effects of growth factors on the maintenance of testicular tissue integrity, germ cell numbers, and potential induction of IVS using a porcine model, we cultured small testicular fragments (~2 mg) from 1-wk-old piglets under six different media conditions (DMEM + 10%KSR alone or supplemented with GDNF, bFGF, SCF, EGF, or a combination of all) for 8 weeks. Overall, tissues supplemented with GDNF and bFGF had the greatest seminiferous tubule integrity and least number of apoptotic cells. GDNF-supplemented tissues had the greatest number of gonocytes per tubule, followed by bFGF-supplemented tissues. There was evidence of gradual Sertoli cell maturation in all groups. Moreover, histological examination and the expression of c-KIT (a marker of differentiating spermatogonia and spermatocytes) and STRA8 (a marker of the pre/meiotic stage germ cells) confirmed the induction of IVS in all groups. However, GDNF- and bFGF-supplemented tissue cultures had greater numbers of seminiferous tubules with spermatocytes compared to other groups. In conclusion, overall, GDNF and bFGF supplementation better maintained the tissue integrity and gonocyte numbers and induced IVS in cultured testicular tissues. Full article
(This article belongs to the Special Issue Male Reproductive Health and Infertility: A Look towards the Future II)
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27 pages, 5318 KiB  
Article
Dysregulation of Immature Sertoli Cell Functions by Exposure to Acetaminophen and Genistein in Rodent Cell Models
by Maia Corpuz-Hilsabeck, Nicole Mohajer and Martine Culty
Cells 2023, 12(13), 1804; https://doi.org/10.3390/cells12131804 - 07 Jul 2023
Cited by 1 | Viewed by 1573
Abstract
Sertoli cells are essential for germ cell development and function. Their disruption by endocrine disrupting chemicals (EDCs) or drugs could jeopardize spermatogenesis, contributing to male infertility. Perinatal exposure to EDCs and acetaminophen (APAP) disrupts male reproductive functions in animals and humans. Infants can [...] Read more.
Sertoli cells are essential for germ cell development and function. Their disruption by endocrine disrupting chemicals (EDCs) or drugs could jeopardize spermatogenesis, contributing to male infertility. Perinatal exposure to EDCs and acetaminophen (APAP) disrupts male reproductive functions in animals and humans. Infants can be exposed simultaneously to the dietary soy phytoestrogen genistein (GEN) and APAP used for fever or pain relief. Our goal was to determine the effects of 10–100 µM APAP and GEN, alone or mixed, on immature Sertoli cells using mouse TM4 Sertoli cell line and postnatal-day 8 rat Sertoli cells, by measuring cell viability, proliferation, prostaglandins, genes and protein expression, and functional pathways. A value of 50 µM APAP decreased the viability, while 100 µM APAP and GEN decreased the proliferation. Sertoli cell and eicosanoid pathway genes were affected by GEN and mixtures, with downregulation of Sox9, Cox1, Cox2, and genes relevant for Sertoli cell function, while genes involved in inflammation were increased. RNA-seq analysis identified p53 and TNF signaling pathways as common targets of GEN and GEN mixture in both cell types. These results suggest that APAP and GEN dysregulate immature Sertoli cell function and may aid in elucidating novel EDC and drug targets contributing to the etiology of male infertility. Full article
(This article belongs to the Special Issue Male Reproductive Health and Infertility: A Look towards the Future II)
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21 pages, 4452 KiB  
Article
Sperm Motility Annotated Genes: Are They Associated with Impaired Fecundity?
by Masood Abu-Halima, Lea Simone Becker, Mohammad A. Al Smadi, Hashim Abdul-Khaliq, Markus Raeschle and Eckart Meese
Cells 2023, 12(9), 1239; https://doi.org/10.3390/cells12091239 - 25 Apr 2023
Cited by 1 | Viewed by 1653
Abstract
Sperm motility is a prerequisite for achieving pregnancy, and alterations in sperm motility, along with sperm count and morphology, are commonly observed in subfertile men. The aim of the study was to determine whether the expression level of genes annotated with the Gene [...] Read more.
Sperm motility is a prerequisite for achieving pregnancy, and alterations in sperm motility, along with sperm count and morphology, are commonly observed in subfertile men. The aim of the study was to determine whether the expression level of genes annotated with the Gene Ontology (GO) term ‘sperm motility’ differed in sperm collected from healthy men and men diagnosed with oligoasthenozoospermia. Reverse transcription quantitative real-time PCR (RT-qPCR), quantitative mass spectrometry (LC-MS/MS), and enrichment analyses were used to validate a set of 132 genes in 198 men present at an infertility clinic. Out of the 132 studied sperm-motility-associated genes, 114 showed differentially expressed levels in oligoasthenozoospermic men compared to those of normozoospermic controls using an RT-qPCR analysis. Of these, 94 genes showed a significantly lower expression level, and 20 genes showed a significantly higher expression level. An MS analysis of sperm from an independent cohort of healthy and subfertile men identified 692 differentially expressed proteins, of which 512 were significantly lower and 180 were significantly higher in oligoasthenozoospermic men compared to those of the normozoospermic controls. Of the 58 gene products quantified with both techniques, 48 (82.75%) showed concordant regulation. Besides the sperm-motility-associated proteins, the unbiased proteomics approach uncovered several novel proteins whose expression levels were specifically altered in abnormal sperm samples. Among these deregulated proteins, there was a clear overrepresentation of annotation terms related to sperm integrity, the cytoskeleton, and energy-related metabolism, as well as human phenotypes related to spermatogenesis and sperm-related abnormalities. These findings suggest that many of these proteins may serve as diagnostic markers of male infertility. Our study reveals an extended number of sperm-motility-associated genes with altered expression levels in the sperm of men with oligoasthenozoospermia. These genes and/or proteins can be used in the future for better assessments of male factor infertility. Full article
(This article belongs to the Special Issue Male Reproductive Health and Infertility: A Look towards the Future II)
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