Male Infertility: New Developments, Current Challenges, and Future Directions

Gül, Murat; Russo, Giorgio Ivan; Kandil, Hussein; Boitrelle, Florence; Saleh, Ramadan; Chung, Eric; Kavoussi, Parviz; Mostafa, Taymour; Shah, Rupin; Agarwal, Ashok

doi:10.5534/wjmh.230232

Cited by 5 publications

(1 citation statement)

References 158 publications

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“…Disorders in gametogenesis can lead to subfertility/infertility, which is a condition that affects a significant portion of the global population. Male infertility accounts for approximately 50% of the cases ( 2 , 3 ), and it is mainly manifested with poor-quality sperm in terms of quantity (oligozoospermia), morphology (globozoospermia), and motility (asthenozoospermia) ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Type 1 diabetes impairs the activity of rat testicular somatic and germ cells through NRF2/NLRP3 pathway-mediated oxidative stress

Venditti,

Romano,

Boccella

et al. 2024

Front. Endocrinol.

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BackgroundIt is well known that metabolic disorders, including type 1 diabetes (T1D), are often associated with reduced male fertility, mainly increasing oxidative stress and impairing the hypothalamus–pituitary–testis (HPT) axis, with consequently altered spermatogenesis and reduced sperm parameters. Herein, using a rat model of T1D obtained by treatment with streptozotocin (STZ), we analyzed several parameters of testicular activity.MethodsA total of 10 adult male Wistar rats were divided into two groups of five: control and T1D, obtained with a single intraperitoneal injection of STZ. After 3 months, the rats were anesthetized and sacrificed; one testis was stored at -80°C for biochemical analysis, and the other was fixed for histological and immunofluorescence analysis.ResultsThe data confirmed that T1D induced oxidative stress and, consequently, alterations in both testicular somatic and germ cells. This aspect was highlighted by enhanced apoptosis, altered steroidogenesis and Leydig cell maturity, and impaired spermatogenesis. In addition, the blood–testis barrier integrity was compromised, as shown by the reduced levels of structural proteins (N-cadherin, ZO-1, occludin, connexin 43, and VANGL2) and the phosphorylation status of regulative kinases (Src and FAK). Mechanistically, the dysregulation of the SIRT1/NRF2/MAPKs signaling pathways was proven, particularly the reduced nuclear translocation of NRF2, affecting its ability to induce the transcription of genes encoding for antioxidant enzymes. Finally, the stimulation of testicular inflammation and pyroptosis was also confirmed, as highlighted by the increased levels of some markers, such as NF-κB and NLRP3.ConclusionThe combined data allowed us to confirm that T1D has detrimental effects on rat testicular activity. Moreover, a better comprehension of the molecular mechanisms underlying the association between metabolic disorders and male fertility could help to identify novel targets to prevent and treat fertility disorders related to T1D.

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Section: Introductionmentioning

confidence: 99%

Type 1 diabetes impairs the activity of rat testicular somatic and germ cells through NRF2/NLRP3 pathway-mediated oxidative stress

Venditti,

Romano,

Boccella

et al. 2024

Front. Endocrinol.

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Potential for artificial intelligence in medicine and its application to male infertility

Kobayashi

2024

Reprod Medicine & Biology

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BackgroundThe third AI boom, which began in 2010, has been characterized by the rapid evolution and diversification of AI and marked by the development of key technologies such as machine learning and deep learning. AI is revolutionizing the medical field, enhancing diagnostic accuracy, surgical outcomes, and drug production.MethodsThis review includes explanations of digital transformation (DX), the history of AI, the difference between machine learning and deep learning, recent AI topics, medical AI, and AI research in male infertility.Main Findings (Results)In research on male infertility, I established an AI‐based prediction model for Johnsen scores and an AI predictive model for sperm retrieval in non‐obstructive azoospermia, both by no‐code AI.ConclusionsAI is making constant progress. It would be ideal for physicians to acquire a knowledge of AI and even create AI models. No‐code AI tools have revolutionized model creation, allowing individuals to independently handle data preparation and model development. Previously a team effort, this shift empowers users to craft customized AI models solo, offering greater flexibility and control in the model creation process.

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Oxidative stress affects sperm health and fertility—Time to apply facts learned at the bench to help the patient: Lessons for busy clinicians

Sengupta,

Pinggera,

Calogero

et al. 2024

Reprod Medicine & Biology

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BackgroundIncreased oxidative stress (OS), resulting from the delicate balance between reactive oxygen species (ROS) production and antioxidant defense, is closely linked to sperm abnormalities and male subfertility. Elevated ROS levels particularly affect sperm quality. The vulnerability of spermatozoa to ROS is due to the absence of DNA repair mechanisms and the high presence of polyunsaturated fatty acids in their membranes.MethodsThis article updates and advances our understanding of the molecular damage caused by OS in spermatozoa, including lipid peroxidation, DNA damage, motility, and functionality. Additionally, the review discusses the challenges in diagnosing OS in semen and recommends accurate and sensitive testing methods. Case studies are utilized to demonstrate the effective management of male infertility caused by OS.Main findingsHighlighting the need to bridge the gap between research and clinical practice, this review suggests strategies for clinicians, such as lifestyle and dietary changes and antioxidant therapies. The review emphasizes lifestyle modifications and personalized care as effective strategies in managing male infertility caused by OS.ConclusionThis review calls for early detection and intervention and interdisciplinary collaboration to improve patient care in male infertility cases related to increased OS.

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Male Infertility: New Developments, Current Challenges, and Future Directions

Cited by 5 publications

References 158 publications

Type 1 diabetes impairs the activity of rat testicular somatic and germ cells through NRF2/NLRP3 pathway-mediated oxidative stress

Type 1 diabetes impairs the activity of rat testicular somatic and germ cells through NRF2/NLRP3 pathway-mediated oxidative stress

Potential for artificial intelligence in medicine and its application to male infertility

Oxidative stress affects sperm health and fertility—Time to apply facts learned at the bench to help the patient: Lessons for busy clinicians

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