Non-obstructive azoospermia: current and future perspectives

Tharakan, Tharu; Luo, Ronnier; Jayasena, Channa N.; Minhas, Suks

doi:10.12703/r/10-7

Cited by 41 publications

(27 citation statements)

References 32 publications

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“…The basic common function of all WD40-repeat proteins is to coordinate the assembly of multi-protein complex, where the repeating units act as a rigid scaffolds for protein interactions 22 . The complex structure of sperm flagella contained a series of WD40-domain-containing proteins 1 , 23 . These proteins including CFAP43 (also known as WDR96 , MIM: 617558), CFAP44 (also known as WDR52 , MIM: 617559) and WDR66 (MIM: 618146) are associated with MMAF and their bi-allelic variants can reduce sperm motility and cause male infertility 24 – 26 .…”

Section: Discussionmentioning

confidence: 99%

Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly

Lü

et al. 2021

Cell Discov

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Inner dynein arm (IDA), composed of a series of protein complex, is necessary to cilia and flagella bend formation and beating. Previous studies indicated that defects of IDA protein complex result in multiple morphological abnormalities of the sperm flagellum (MMAF) and male infertility. However, the genetic causes and molecular mechanisms in the IDAs need further exploration. Here we identified two loss-of-function variants of WDR63 in both MMAF and non-obstructive azoospermia (NOA) affected cohorts. WDR63 encodes an IDA-associated protein that is dominantly expressed in testis. We next generated Wdr63-knockout (Wdr63-KO) mice through the CRISPR-Cas9 technology. Remarkably, Wdr63-KO induced decreased sperm number, abnormal flagellar morphology and male infertility. In addition, transmission electron microscopy assay showed severely disorganized “9 + 2” axoneme and absent inner dynein arms in the spermatozoa from Wdr63-KO male mice. Mechanistically, we found that WDR63 interacted with WDR78 mainly via WD40-repeat domain and is necessary for IDA assembly. Furthermore, WDR63-associated male infertility in human and mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. In conclusion, the present study demonstrates that bi-allelic variants of WDR63 cause male infertility via abnormal inner dynein arms assembly and flagella formation and can be used as a genetic diagnostic indicator for infertility males.

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Section: Discussionmentioning

confidence: 99%

Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly

Lü

et al. 2021

Cell Discov

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“…However, the reason for the lack of a statistically signi cant difference in T/E2 between successful and unsuccessful sperm retrieval by micro TESE is unknown. So far, various clinical and hormone parameters have been investigated as potential predictors of successful sperm retrieval but the evidence for clinical and biochemical markers is con icting 19 . One study found that a decreased seminal testosterone/estradiol ratio could be a good indicator for identifying absence of sperm production in NOA patients 27 .…”

Section: Discussionmentioning

confidence: 99%

AI model developed using machine learning for predicting sperm retrieval in micro TESE for non-obstructive azoospermia patients

Kobayashi

Uetani

Yamabe

et al. 2022

Preprint

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Azoospermia is a severe problem that prevents couples from having their own children through natural pregnancy. To obtain sperm from patients with azoospermia testicular sperm extraction (TESE) is required. In non-obstructive azoospermia (NOA), a particularly severe type of male infertility, patients need to undergo microdissection testicular sperm extraction (micro TESE) to collect sperm and, at 40 to 60%, the sperm retrieval success rate is not very high. Therefore, our objective in the present study was to make a model for predicting the possibility of sperm retrieval in patients with NOA before performing micro TESE, using machine learning. We retrospectively obtained data from the medical records of 430 patients who underwent micro TESE from 2011 to 2020, and used Prediction One, which does not require coding, to create the model. We successfully achieved our objective. The AUC for the AI model was 0.7246, which is acceptable. In addition, among the variables, we found that T/E2 ratios contributed most to predicting whether sperm retrieval was possible or not. T/E2 ratios have potential as a clinical predictor of sperm retrieval in NOA.

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“…Men with NOA must undergo surgical sperm retrieval and intracytoplasmic sperm injection in order to father biological children, and the live birth rate is ~25% [ 32 ]. Artificial intelligence and predictive modelling may aid in increasing the sperm retrieval rate in men with NOA [ 33 ]. Additionally, several promising experimental techniques to restore fertility in men with NOA are currently in the research ‘pipeline’, including transplantation of spermatogonial stem cells, differentiation of adult or embryonic stem cells, and gene therapy [ 34 ].…”

Section: Future Perspectives In Azoospermiamentioning

confidence: 99%

Current updates and future perspectives in the evaluation of azoospermia: A systematic review

Punjani

Kang

Lamb³

2021

Arab Journal of Urology

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Objectives: To provide a summary of the current evaluation of azoospermia and insights into future perspectives in the evaluation and counselling of men with azoospermia. Methods: A search of PubMed, Cochrane Reviews and Web of Science databases was performed for full-text English-language articles published between 1943 and 2020 focussing on 'future perspectives', 'azoospermia' and 'evaluation'. Results: Azoospermia represents a severe form of male infertility characterised by sperm production so impaired that there are no sperm present in the ejaculate. The current evaluation of azoospermia focusses on patient history and physical examination with selected adjunctive laboratory investigations including serum hormones, a karyotype and screening for Y chromosome microdeletions. Future diagnostics are focussed on identifying the underlying genetic aetiologies for azoospermia, as well as a greater emphasis on screening for systemic illness that men with severe infertility may be predisposed to develop. Conclusion:Azoospermia represents an extreme form of male infertility, and evaluation relies heavily on history and physical examination, as genetic evaluations for these individuals remain limited. Future evaluation will focus on next-generation sequencing and more rigorous evaluation for possible co-existing and future risk of systemic disease.

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Non-obstructive azoospermia: current and future perspectives

Cited by 41 publications

References 32 publications

Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly

Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly

AI model developed using machine learning for predicting sperm retrieval in micro TESE for non-obstructive azoospermia patients

Current updates and future perspectives in the evaluation of azoospermia: A systematic review

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