Life | Topical Collection : Male Infertility: Current Knowledge and Future Perspectives

2023

Jump to: 2022, 2021

13 pages, 2714 KiB

Open AccessArticle

Successful Production of Offspring Derived from Phospholipase C Zeta-Deficient Sperm by Additional Artificial Activation

by Naoki Hirose, Yasuyuki Kikuchi, Atsuko Kageyama, Hibiki Sugita, Miu Sakurai, Yui Kawata, Jumpei Terakawa, Teruhiko Wakayama, Junya Ito and Naomi Kashiwazaki

Life 2023, 13(4), 980; https://doi.org/10.3390/life13040980 - 10 Apr 2023

Cited by 4 | Viewed by 2392

Abstract

During mammalian fertilization, repetitive rises of intracellular calcium called calcium oscillations are required for full activation of oocytes. Therefore, oocytes such as round spermatid injected or somatic cell nuclear transferred require additional artificial activation which mimics the calcium oscillations. It is well recognized [...] Read more.

During mammalian fertilization, repetitive rises of intracellular calcium called calcium oscillations are required for full activation of oocytes. Therefore, oocytes such as round spermatid injected or somatic cell nuclear transferred require additional artificial activation which mimics the calcium oscillations. It is well recognized that sperm specific phospholipase C (PLCζ) is a strong candidate as the sperm factor which can induce calcium oscillations and, at least in mammals, the genetic mutation of PLCζ in human causes male infertility due to the lack of calcium oscillations in the oocytes. Recent studies showed that the sperm lacking PLCζ (Plcz1^−/−) still could induce rise(s) of intracellular calcium in the oocytes after IVF but not intracytoplasmic sperm injection (ICSI). In the ICSI oocytes, no pronuclear formation or development to the two-cell stage was observed. However, it is still unclear whether additional activation treatment can rescue the low developmental ability of Plcz1^−/−-sperm-derived oocytes after ICSI. In this study, we examined whether oocytes injected with a Plcz1^−/− sperm can develop to term by additional artificial activation. In oocytes injected a Plcz1^−/− sperm and Plcz1^−/− and eCS (another candidate of the sperm factor) double knockout sperm (Plcz1^−/−eCS^−/−), the rates of pronuclear formation were very low (2.0 ± 2.3% and 6.1 ± 3.7%, respectively) compared to control (92.1 ± 2.6%). However, these rates were dramatically improved by additional procedures of PLCζ-mRNA injection or SrCl₂ treatment (Plcz1^−/− sperm + PLCζ mRNA, Plcz1^−/− sperm + SrCl₂ and Plcz1^−/−eCS^−/− sperm + PLCζ mRNA; 64.2 ± 10.8%, 89.2 ± 2.4% and 72.6 ± 5.4%, respectively). Most of the oocytes were developed to the two-cell stage. After embryo transfer, healthy pups were obtained in all these groups (Plcz1^−/− sperm + PLCζ mRNA:10.0 ± 2.8%, Plcz1^−/− sperm + SrCl₂:4.0 ± 4.3% and Plcz1^−/−eCS^−/− sperm + PLCζ mRNA: 10.0 ± 5.7%). The rate in Plcz1^−/− sperm + SrCl₂ group was significantly lower than that in control (26.0 ± 2.4%). Taken together, our present results show that additional activation treatment such as SrCl₂ and PLCζ mRNA can fully support to develop to term even in oocyte injected Plcz1^−/− sperm. In addition, PLCζ-induced oocyte activation is more suitable for successful development to term compared to that such as phenomenon induced by SrCl₂. These findings will contribute to improvement for male-dependent human infertility and reproductive technologies in other mammalian species. Full article

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25 pages, 3293 KiB

Open AccessSystematic Review

Analytical Determination of Heavy Metals in Human Seminal Plasma—A Systematic Review

by Andrea López-Botella, Raquel Sánchez, Raiza Paul, Jon Aizpurua, María José Gómez-Torres and José-Luis Todolí-Torró

Life 2023, 13(4), 925; https://doi.org/10.3390/life13040925 - 31 Mar 2023

Cited by 7 | Viewed by 2350

Abstract

Infertility is a growing concerning health problem affecting around 15% of couples worldwide. Conventional semen parameters have limited accuracy for male infertility potential determination. Current advances in the understanding of male infertility indicate that environmental and occupational exposure to chemical contaminants are important [...] Read more.

Infertility is a growing concerning health problem affecting around 15% of couples worldwide. Conventional semen parameters have limited accuracy for male infertility potential determination. Current advances in the understanding of male infertility indicate that environmental and occupational exposure to chemical contaminants are important etiological factors leading to infertility problems. In this context, some heavy metals (HMs) can be considered as endocrine-disrupting compounds (EDCs), thus altering the seminal quality. This systematic review aims to summarize the key points to detect and quantify HMs in human seminal plasma (SP) and the involved analytical tools. Our results showed that that for HM quantification, atomic absorption spectroscopy (AAS) and inductively coupled plasma (ICP) were the most employed techniques while Zn, Cd, Pb, and Cr were the analytes most often detected. Fast, reliable, and sensitive quantification of EDCs in SP could be important for the development of accurate diagnostic and preventive strategies to address male infertility towards providing personalized therapy. Full article

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2022

Jump to: 2023, 2021

13 pages, 761 KiB

Open AccessArticle

Human Papillomavirus (HPV) Infection and Its Impact on Male Infertility

by Giuseppina Capra, Tiziana Notari, Michela Buttà, Nicola Serra, Giovanni Rizzo and Liana Bosco

Life 2022, 12(11), 1919; https://doi.org/10.3390/life12111919 - 18 Nov 2022

Cited by 16 | Viewed by 4469

Abstract

Nowadays, the striking numbers of infertile couples that turn to assisted reproductive technologies (ART) drive the research toward a more comprehensive understanding of the underlying causes. Male factors contribute to the inability to conceive in half of the cases, and it has been [...] Read more.

Nowadays, the striking numbers of infertile couples that turn to assisted reproductive technologies (ART) drive the research toward a more comprehensive understanding of the underlying causes. Male factors contribute to the inability to conceive in half of the cases, and it has been suggested that sexually transmitted infections could have a role in the onset of spermatozoa impairments. Since the impact of HPV infection on sperm quality and sperm DNA integrity is debated, we wanted to analyze its impact on conventional seminal parameters and the sperm DNA fragmentation index (DFI). Therefore, 117 semen samples of patients undergoing IVF were evaluated for the following characteristics: HPV DNA detection and sperm DNA fragmentation, concentration, motility, and morphology. The results showed a higher rate of HPV-negative patients (59.8% vs. 40.2%) and no HPV-related effect on DFI, sperm concentration, total sperm number, and total motility. Only progressive motility and morphology were found as significantly influenced by HPV positivity. Moreover, we observed a statistically significant difference in DFI when comparing high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Our data suggest that the presence of any HPV type, whatever the exact localization of the virions, can impair some sperm parameters, while HR-HPVs specifically affect the integrity of spermatozoa DNA. Full article

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11 pages, 1963 KiB

Open AccessArticle

Correlation between Cytogenetic Findings and Spermatogenic Failure in Bulgarian Infertile Men

by Svetlana Yovinska, Kalina Belemezova, Mariela Hristova-Savova, Tanya Milachich, Petya Andreeva, Lachezara Veleva, Yuri Buchvarov, Maria Yunakova, Tanya Timeva, Atanas Shterev and Ivanka Dimova

Life 2022, 12(11), 1840; https://doi.org/10.3390/life12111840 - 9 Nov 2022

Cited by 1 | Viewed by 1815

Abstract

The aim of our study was to determine the type and frequency of chromosomal aberrations and polymorphisms in men with different degrees of spermatogenic failure in comparison to men with normozoospermia, in order to find correlations between cytogenetic findings and the abnormal results [...] Read more.

The aim of our study was to determine the type and frequency of chromosomal aberrations and polymorphisms in men with different degrees of spermatogenic failure in comparison to men with normozoospermia, in order to find correlations between cytogenetic findings and the abnormal results of semen analysis. In our study, we performed cytogenetic analysis in 901 infertile men, divided into five groups according to semen analysis—normozoospermia (86), asthenozoospermia (394), oligoasthenozoospermia (182), severe male factor (100), and azoospermia (139). The frequency of polymorphisms was similar in all groups (11–16%, without significant differences). The frequency of numerical and structural aberrations increases with the degree of the spermatogenic failure (3.5% in normozoospermia, 5.6% in asthenozoospermia, 9.8% in oligoasthenozoospermia, 9% in severe male factor, and 13.5% in azoospermia). We found a significantly higher incidence of numerical chromosomal aberrations in severe male factor (7%) and azoospermia (9.3%). Oligoasthenozoospermia occured in 45% of cases with translocation, compared to 20% in the group with a normal karyotype. We revealed that chromosomal translocations are tightly associated with oligoasthenozoospermia, whereas numerical chromosomal aberrations—with severe male factor and azoospermia. The impact of chromosome polymorphisms on male infertility should be studied in greater detail. Full article

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2 pages, 166 KiB

Open AccessReply

Reply to Pallotti et al. Comment on “Boitrelle et al. The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis. Life 2021, 11, 1368”

by Florence Boitrelle, Rupin Shah, Ramadan Saleh, Ralf Henkel, Hussein Kandil, Eric Chung, Paraskevi Vogiatzi, Armand Zini, Mohamed Arafa and Ashok Agarwal

Life 2022, 12(7), 1046; https://doi.org/10.3390/life12071046 - 13 Jul 2022

Cited by 2 | Viewed by 1436

Abstract

We would like to thank F. Pallotti and his colleagues for their positive comments [...] Full article

2 pages, 169 KiB

Open AccessComment

Comment on Boitrelle et al. The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis. Life 2021, 11, 1368

by Francesco Pallotti, Francesco Lombardo and Donatella Paoli

Life 2022, 12(7), 1044; https://doi.org/10.3390/life12071044 - 13 Jul 2022

Cited by 2 | Viewed by 1398

Abstract

We wish to congratulate Boitrelle and colleagues for their comprehensive critical review on the Sixth Edition of the WHO Laboratory Manual for Human semen examination [...] Full article

12 pages, 2770 KiB

Open AccessArticle

Effect of Malignancy on Semen Parameters

by Guy Shrem, Liat Azani, Ido Feferkorn, Tamar Listovsky, Sofia Hussaini, Benjamin Farber, Michael H. Dahan and Mali Salmon-Divon

Life 2022, 12(6), 922; https://doi.org/10.3390/life12060922 - 20 Jun 2022

Cited by 2 | Viewed by 2029

Abstract

Purpose: We aimed to examine how various types of cancer, classified histologically, affect semen quality. Methods: The study group included 313 patients who were diagnosed with cancer and reached for a sperm cryopreservation before a gonadotoxic treatment (PG-Tx group). Their semen parameters were [...] Read more.

Purpose: We aimed to examine how various types of cancer, classified histologically, affect semen quality. Methods: The study group included 313 patients who were diagnosed with cancer and reached for a sperm cryopreservation before a gonadotoxic treatment (PG-Tx group). Their semen parameters were compared to those of two control groups: (a) individuals who attended a fertility investigation and were found to be above the limit of the lower reference value of the WHO 2010 manual (ARL group), and (b) fertile men, whose semen parameters were obtained from the dataset of the WHO 2020 manual. Results: Semen quality was significantly poorer in the PG-Tx group than in the ARL group. Differences included a 65.6% decrease in concentration, a 12.1% decrease in volume, a 72.7% decrease in total count, and a 33.0%, 22.2%, and 24.7% decrease in total motility, rapid motility, and progressive motility, respectively. Linear regression models comparing the PG-Tx and ARL groups revealed that the maximum reduction in total motility and concentration was in men with germ-cell tumors, whereas the minimum reduction was in hematological tumors. Similarly, all sperm quality parameters were significantly lower in the PG-Tx group than in the fertile-men group (p < 0.0001). Conclusions: While the effect of malignancy on semen parameters is debatable, we found that all examined types of cancer significantly impaired sperm quality parameters. Although the median of most semen parameters of patients with cancer were still in the normal WHO range, their fifth percentile, represents men with a delayed time to pregnancy. Full article

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19 pages, 3409 KiB

Open AccessArticle

Concerns with Male Infertility Induced by Exposure to Titanium Nanoparticles and the Supporting Impact of Pelargonium graveolens Essential Oil: Morphometric Records in Male-Wistar Rats

by Ahmed Abdou Said, Yasmin Nasr, Azza A. A. Galal, Ahmed E. Abdelhamid, Haiam A. Mohamed, Mohamed M. M. Metwally, Mahmoud A. Said, Mohamed A. Nassan, Naief Dahran and Amany Abdel-Rahman Mohamed

Life 2022, 12(5), 639; https://doi.org/10.3390/life12050639 - 26 Apr 2022

Cited by 10 | Viewed by 4299

Abstract

Background: Due to the increased use of titanium dioxide nanoparticles (TiO₂ NPs), the risks of their reprotoxic effect arise. This study anticipated examining the potential protective effects of GEO (geranium essential oil) components screened via GC/MS analysis against the reprotoxic impacts [...] Read more.

Background: Due to the increased use of titanium dioxide nanoparticles (TiO₂ NPs), the risks of their reprotoxic effect arise. This study anticipated examining the potential protective effects of GEO (geranium essential oil) components screened via GC/MS analysis against the reprotoxic impacts of TiO₂ NPs on male rats. Methods: Thirty-two adult male rats were randomly assigned to four groups: control, GEO (75 mg/kg bwt/orally/day/60 days), TiO₂ NPs (100 ppm/rat/IP/day/60 days), and TiO₂ NPs + GEO. After 60 days, hormonal assay, semen appraisal, lipid peroxidation, antioxidant enzymes, testis and prostate morphometry, and the steroidogenesis-related genes’ mRNA expressions were assessed. Results: The TEM and DLS results demonstrated that synthesized TiO₂ NPs are spherical with minimal aggregations polydispersed and varying in size from 50 to 100 nm. TiO₂ NPs IP injection-induced sperm abnormalities decreased the percent of motile sperms in the sperm count, reduced sex hormone levels, altered the testicular oxidant/antioxidant status and mRNA expression of steroid-related genes, and induced architectural alterations in testicular, epididymal, and prostate gland tissues. GEO significantly rescued the TiO₂ NPs-altered spermiogram, sex hormones, and antioxidant capacity, restored the tissue architectures, and enhanced steroidogenesis-related gene mRNA expression. Conclusions: These findings may significantly contribute to developing combinatorial treatments for infertility associated with various environmental and industrial xenobiotic exposures. Full article

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29 pages, 2013 KiB

Open AccessReview

The Fate of Leydig Cells in Men with Spermatogenic Failure

by Daria Adamczewska, Jolanta Słowikowska-Hilczer and Renata Walczak-Jędrzejowska

Life 2022, 12(4), 570; https://doi.org/10.3390/life12040570 - 12 Apr 2022

Cited by 20 | Viewed by 9586

Abstract

The steroidogenic cells in the testicle, Leydig cells, located in the interstitial compartment, play a vital role in male reproductive tract development, maintenance of proper spermatogenesis, and overall male reproductive function. Therefore, their dysfunction can lead to all sorts of testicular pathologies. Spermatogenesis [...] Read more.

The steroidogenic cells in the testicle, Leydig cells, located in the interstitial compartment, play a vital role in male reproductive tract development, maintenance of proper spermatogenesis, and overall male reproductive function. Therefore, their dysfunction can lead to all sorts of testicular pathologies. Spermatogenesis failure, manifested as azoospermia, is often associated with defective Leydig cell activity. Spermatogenic failure is the most severe form of male infertility, caused by disorders of the testicular parenchyma or testicular hormone imbalance. This review covers current progress in knowledge on Leydig cells origin, structure, and function, and focuses on recent advances in understanding how Leydig cells contribute to the impairment of spermatogenesis. Full article

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12 pages, 1550 KiB

Open AccessArticle

Inhibin-B and FSH Are Good Indicators of Spermatogenesis but Not the Best Indicators of Fertility

by Katarzyna Jankowska, Natalia Suszczewicz, Michał Rabijewski, Piotr Dudek, Wojciech Zgliczyński and Radosław B. Maksym

Life 2022, 12(4), 511; https://doi.org/10.3390/life12040511 - 30 Mar 2022

Cited by 9 | Viewed by 7474

Abstract

Biochemical markers of spermatogenesis and fertility assessment are important in the practical management of infertile males and the determination of an individual’s prognosis. We performed an analysis on 100 males with a male infertility factor. The following study inclusion parameters were analyzed: seminogram, [...] Read more.

Biochemical markers of spermatogenesis and fertility assessment are important in the practical management of infertile males and the determination of an individual’s prognosis. We performed an analysis on 100 males with a male infertility factor. The following study inclusion parameters were analyzed: seminogram, FSH, LH, testosterone, estradiol, prolactin, TSH, and inhibin B concentrations. The patients were subsequently treated by reproductive endocrinologists in accordance with AUA/ASRM and EAU guidelines. The reproductive status was evaluated over a period of 3 years. We found a strong correlation of sperm count with inhibin B (r = 0.74, p < 0.001) and FSH concentration levels (r = −0.46, p < 0.001). Among 95 patients at follow-up, pregnancies occurred for 59 of their partners (48 spontaneous, 5 after IVF–ET, and 6 after IUI). Thirty-six patients remained childless despite the therapy. Sperm count and inhibin B level were the best predictors of natural fertilization (ROC AUC: 0.86 and 0.84; cut-off: 2.7 mln/mL and 45 pg/mL). Although inhibin B and FSH can be used to evaluate spermatogenesis and fertility, the initial sperm concentration appeared to be the best predictor of success. Pregnancy was achieved in a surprisingly large proportion of patients with a very low concentration of inhibin B and a low initial sperm count. It is noteworthy that 81% of the pregnancies were achieved without medically assisted reproduction. Full article

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21 pages, 1289 KiB

Open AccessReview

Omics and Male Infertility: Highlighting the Application of Transcriptomic Data

by Temidayo S. Omolaoye, Victor A. Omolaoye, Richard K. Kandasamy, Mahmood Yaseen Hachim and Stefan S. Du Plessis

Life 2022, 12(2), 280; https://doi.org/10.3390/life12020280 - 14 Feb 2022

Cited by 23 | Viewed by 5021

Abstract

Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples. Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because [...] Read more.

Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples. Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques. Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the “omics” perspective. Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated. After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis. These datasets were classified into groups according to the disease or cause of male infertility. The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion. Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups. Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3). These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes. Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility. Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases. Full article

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19 pages, 7658 KiB

Open AccessArticle

Accurate Quantitative Histomorphometric-Mathematical Image Analysis Methodology of Rodent Testicular Tissue and Its Possible Future Research Perspectives in Andrology and Reproductive Medicine

by Réka Eszter Sziva, Júlia Ács, Anna-Mária Tőkés, Ágnes Korsós-Novák, György L. Nádasy, Nándor Ács, Péter Gábor Horváth, Anett Szabó, Haoran Ke, Eszter Mária Horváth, Zsolt Kopa and Szabolcs Várbíró

Life 2022, 12(2), 189; https://doi.org/10.3390/life12020189 - 27 Jan 2022

Cited by 11 | Viewed by 8263

Abstract

Infertility is increasing worldwide; male factors can be identified in nearly half of all infertile couples. Histopathologic evaluation of testicular tissue can provide valuable information about infertility; however, several different evaluation methods and semi-quantitative score systems exist. Our goal was to describe a [...] Read more.

Infertility is increasing worldwide; male factors can be identified in nearly half of all infertile couples. Histopathologic evaluation of testicular tissue can provide valuable information about infertility; however, several different evaluation methods and semi-quantitative score systems exist. Our goal was to describe a new, accurate and easy-to-use quantitative computer-based histomorphometric-mathematical image analysis methodology for the analysis of testicular tissue. On digitized, original hematoxylin-eosin (HE)-stained slides (scanned by slide-scanner), quantitatively describable characteristics such as area, perimeter and diameter of testis cross-sections and of individual tubules were measured with the help of continuous magnification. Immunohistochemically (IHC)-stained slides were digitized with a microscope-coupled camera, and IHC-staining intensity measurements on digitized images were also taken. Suggested methods are presented with mathematical equations, step-by-step detailed characterization and representative images are given. Our novel quantitative histomorphometric-mathematical image analysis method can improve the reproducibility, objectivity, quality and comparability of andrological-reproductive medicine research by recognizing even the mild impairments of the testicular structure expressed numerically, which might not be detected with the present semi-quantitative score systems. The technique is apt to be subjected to further automation with machine learning and artificial intelligence and can be named ‘Computer-Assisted or -Aided Testis Histology’ (CATHI). Full article

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2021

Jump to: 2023, 2022

23 pages, 817 KiB

Open AccessReview

Endocrinopathies and Male Infertility

by Pallav Sengupta, Sulagna Dutta, Ivan Rolland Karkada and Suresh V. Chinni

Life 2022, 12(1), 10; https://doi.org/10.3390/life12010010 - 22 Dec 2021

Cited by 31 | Viewed by 10596

Abstract

Male infertility is approaching a concerning prevalence worldwide, and inflicts various impacts on the affected couple. The hormonal assessment is a vital component of male fertility evaluation as endocrine disorders are markedly reversible causatives of male infertility. Precise hormonal regulations are prerequisites to [...] Read more.

Male infertility is approaching a concerning prevalence worldwide, and inflicts various impacts on the affected couple. The hormonal assessment is a vital component of male fertility evaluation as endocrine disorders are markedly reversible causatives of male infertility. Precise hormonal regulations are prerequisites to maintain normal male fertility parameters. The core male reproductive event, spermatogenesis, entails adequate testosterone concentration, which is produced via steroidogenesis in the Leydig cells. Physiological levels of both the gonadotropins are needed to achieve normal testicular functions. The hypothalamus-derived gonadotropin-releasing hormone (GnRH) is considered the supreme inducer of the gonadotropins and thereby the subsequent endocrine reproductive events. This hypothalamic–pituitary–gonadal (HPG) axis may be modulated by the thyroidal or adrenal axis and numerous other reproductive and nonreproductive hormones. Disruption of this fine hormonal balance and their crosstalk leads to a spectrum of endocrinopathies, inducing subfertility or infertility in men. This review article will discuss the most essential endocrinopathies associated with male factor infertility to aid precise understanding of the endocrine disruptions-mediated male infertility to encourage further research to reveal the detailed etiology of male infertility and perhaps to develop more customized therapies for endocrinopathy-induced male infertility. Full article

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13 pages, 968 KiB

Open AccessReview

The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis

by Florence Boitrelle, Rupin Shah, Ramadan Saleh, Ralf Henkel, Hussein Kandil, Eric Chung, Paraskevi Vogiatzi, Armand Zini, Mohamed Arafa and Ashok Agarwal

Life 2021, 11(12), 1368; https://doi.org/10.3390/life11121368 - 9 Dec 2021

Cited by 112 | Viewed by 17112

Abstract

Semen analysis is the cornerstone of male fertility evaluation with WHO guidelines providing the basis for procedural standardization and reference values worldwide. The first WHO manual was published in 1980, and five editions have been subsequently released over the last four decades. The [...] Read more.

Semen analysis is the cornerstone of male fertility evaluation with WHO guidelines providing the basis for procedural standardization and reference values worldwide. The first WHO manual was published in 1980, and five editions have been subsequently released over the last four decades. The 6th Edition was published in July 2021. In this review, we identify the key changes of this 6th Edition. Additionally, we evaluate the utility of this 6th Edition in clinical practice using SWOT (strengths, weaknesses, opportunities, and threats) analysis. This new Edition has made the analysis of basic semen parameters more robust, taking into account the criticisms and grey areas of the previous editions. The tests assessing sperm DNA fragmentation and seminal oxidative stress are well-described. The main novelty is that this latest edition abandons the notion of reference thresholds, suggesting instead to replace them with “decision limits”. While this seems attractive, no decision limits are proposed for either basic semen parameters, or for extended or advanced parameters. This critical review of the 6th Edition of the WHO laboratory manual combined with a SWOT analysis summarizes the changes and novelties present in this new Edition and provides an in-depth analysis that could help its global use in the coming years. Full article

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17 pages, 9616 KiB

Open AccessArticle

Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?

by Dinko Hauptman, Marta Himelreich Perić, Tihana Marić, Ana Katušić Bojanac, Nino Sinčić, Zoran Zimak, Željko Kaštelan and Davor Ježek

Life 2021, 11(11), 1266; https://doi.org/10.3390/life11111266 - 19 Nov 2021

Cited by 8 | Viewed by 3293

Abstract

Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 [...] Read more.

Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells. Full article

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29 pages, 5190 KiB

Open AccessArticle

Progesterone, Myo-Inositol, Dopamine and Prolactin Present in Follicular Fluid Have Differential Effects on Sperm Motility Subpopulations

by Shannen Keyser, Gerhard van der Horst and Liana Maree

Life 2021, 11(11), 1250; https://doi.org/10.3390/life11111250 - 17 Nov 2021

Cited by 9 | Viewed by 4244

Abstract

Considering the challenges surrounding causative factors in male infertility, rather than relying on standard semen analysis, the assessment of sperm subpopulations and functional characteristics essential for fertilization is paramount. Furthermore, the diagnostic value of sperm interactions with biological components in the female reproductive [...] Read more.

Considering the challenges surrounding causative factors in male infertility, rather than relying on standard semen analysis, the assessment of sperm subpopulations and functional characteristics essential for fertilization is paramount. Furthermore, the diagnostic value of sperm interactions with biological components in the female reproductive tract may improve our understanding of subfertility and provide applications in assisted reproductive techniques. We investigated the response of two sperm motility subpopulations (mimicking the functionality of potentially fertile and sub-fertile semen samples) to biological substances present in the female reproductive tract. Donor semen was separated via double density gradient centrifugation, isolated into high (HM) and low motile (LM) sperm subpopulations and incubated in human tubal fluid (HTF), capacitating HTF, HD-C medium, progesterone, myo-inositol, dopamine and prolactin. Treated subpopulations were evaluated for vitality, motility percentages and kinematic parameters, hyperactivation, positive reactive oxygen species (ROS), intact mitochondrial membrane potential (MMP) and acrosome reaction (AR). While all media had a significantly positive effect on the LM subpopulation, dopamine appeared to significantly improve both subpopulations’ functional characteristics. HD-C, progesterone and myo-inositol resulted in increased motility, kinematic and hyperactivation parameters, whereas prolactin and myo-inositol improved the LM subpopulations’ MMP intactness and reduced ROS. Furthermore, progesterone, myo-inositol and dopamine improved the HM subpopulations’ motility parameters and AR. Our results suggest that treatment of sub-fertile semen samples with biological substances present in follicular fluid might assist the development of new strategies for IVF treatment. Full article

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9 pages, 714 KiB

Open AccessArticle

Sperm Selection and Embryo Development: A Comparison of the Density Gradient Centrifugation and Microfluidic Chip Sperm Preparation Methods in Patients with Astheno-Teratozoospermia

by Cagla Guler, Sureyya Melil, Umit Ozekici, Yaprak Donmez Cakil, Belgin Selam and Mehmet Cincik

Life 2021, 11(9), 933; https://doi.org/10.3390/life11090933 - 7 Sep 2021

Cited by 10 | Viewed by 4955

Abstract

In recent years, microfluidic chip-based sperm sorting has emerged as an alternative tool to centrifugation-based conventional techniques for in vitro fertilization. This prospective study aims to compare the effects of density gradient centrifugation and microfluidic chip sperm preparation methods on embryo development in [...] Read more.

In recent years, microfluidic chip-based sperm sorting has emerged as an alternative tool to centrifugation-based conventional techniques for in vitro fertilization. This prospective study aims to compare the effects of density gradient centrifugation and microfluidic chip sperm preparation methods on embryo development in patient populations with astheno-teratozoospermia. In the study, the semen samples of the patients were divided into two groups for preparation with either the microfluidic or density gradient methods. Selected spermatozoa were then used to fertilize mature sibling oocytes and the semen parameters and embryo development on days 3 and 5 were assessed. While the density gradient group was associated with a higher sperm concentration, motility (progressive and total) was significantly higher in the microfluidic chip group. No significant differences were observed in the fertilization rates or grade 1 (G1) and grade 2 (G2) proportions of the third-day embryos. Furthermore, while the proportions of the poor, fair and good blastocysts on day 5 did not differ significantly, excellent blastocysts (indicating high-quality embryos) were observed in a significantly higher proportion of the microfluidic chip group. When compared to the classical density gradient method, the microfluidic chip sperm preparation yielded sperm with higher motility and higher quality blastocysts at day 5; in patients with astheno-teratozoospermia. Full article

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16 pages, 950 KiB

Open AccessArticle

Molecular Analysis of DPY19L2, PICK1 and SPATA16 in Italian Unrelated Globozoospermic Men

by Fabiana Faja, Francesco Pallotti, Francesco Cargnelutti, Giulia Senofonte, Tania Carlini, Andrea Lenzi, Francesco Lombardo and Donatella Paoli

Life 2021, 11(7), 641; https://doi.org/10.3390/life11070641 - 30 Jun 2021

Cited by 8 | Viewed by 2812

Abstract

This study aims to evaluate genetic contribution and sperm DNA fragmentation (SDF) in a cohort of 18 unrelated globozoospermic Italian men (Group G). Semen samples were assessed according to the WHO 2010 Laboratory Manual and compared with 31 fertile controls. We focused our [...] Read more.

This study aims to evaluate genetic contribution and sperm DNA fragmentation (SDF) in a cohort of 18 unrelated globozoospermic Italian men (Group G). Semen samples were assessed according to the WHO 2010 Laboratory Manual and compared with 31 fertile controls. We focused our genetic analysis on the exons of the main globozoospermia-associated genes, performing qualitative PCR to assess deletion of DPY19L2 and sequencing to detect mutations of SPATA16 and PICK1. SDF was evaluated using the TUNEL assay. In Group G, 10 patients had a complete form of globozoospermia, whereas 8 patients had a partial form. Molecular analysis revealed deletion of DPY19L2 in six of the patients, all of them with complete globozoospermia, while no mutations were found in the examined exons of PICK1 and SPATA16. TUNEL analysis showed a higher SDF% in Group G. Our findings confirm DPY19L2 defects as the most frequent genetic alteration in Italian patients contributing to globozoospermic phenotypes. Furthermore, spermatozoa with acrosomal defects could also display high levels of SDF as a possible consequence of abnormally remodeled chromatin. The possible effect on offspring of chromatin structure abnormalities and altered DNA integrity should be carefully evaluated by clinicians, especially regarding the feasibility and safety of artificial reproductive techniques, which represent the only treatment that allows these patients to conceive. Full article

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13 pages, 642 KiB

Open AccessReview

Idiopathic Infertility as a Feature of Genome Instability

by Agrita Puzuka, Baiba Alksere, Linda Gailite and Juris Erenpreiss

Life 2021, 11(7), 628; https://doi.org/10.3390/life11070628 - 29 Jun 2021

Cited by 13 | Viewed by 4093

Abstract

Genome instability may play a role in severe cases of male infertility, with disrupted spermatogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, [...] Read more.

Genome instability may play a role in severe cases of male infertility, with disrupted spermatogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, the causes and consequences, and the methods for assessment of genome instability. Male infertility research has provided evidence that spermatogenic defects are often not limited to testicular dysfunction. An increased incidence of urogenital disorders and several types of cancer, as well as overall reduced health (manifested by decreased life expectancy and increased morbidity) have been reported in infertile men. The pathophysiological link between decreased life expectancy and male infertility supports the notion of male infertility being a systemic rather than an isolated condition. It is driven by the accumulation of DNA strand breaks and premature cellular senescence. We have presented extensive data supporting the notion that genome instability can lead to severe male infertility termed “idiopathic oligo-astheno-teratozoospermia.” We have detailed that genome instability in men with oligo-astheno-teratozoospermia (OAT) might depend on several genetic and epigenetic factors such as chromosomal heterogeneity, aneuploidy, micronucleation, dynamic mutations, RT, PIWI/piRNA regulatory pathway, pathogenic allelic variants in repair system genes, DNA methylation, environmental aspects, and lifestyle factors. Full article

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Male Infertility: Current Knowledge and Future Perspectives

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