Genetic defects in human azoospermia

Ghieh, Farah; Mitchell, Valérie; Mandon‐Pepin, Béatrice; Vialard, François

doi:10.1186/s12610-019-0086-6

Cited by 49 publications

(43 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it is also worth noting that it may be possible that genes required for male fertility in mice may not necessarily be required for male fertility in humans. Of the seventy-three human reproductive tract-specific genes our study identified with male mouse infertility phenotypes, twenty-seven genes— ACTL7B [ 53 ], AKAP4 [ 54 ], BOLL [ 55 ], BRDT [ 55 – 60 ], CATSPER4 [ 54 ], CCDC155 [ 61 ], FKBP6 [ 55 , 61 – 63 ], MEIG1 [ 64 ], MEIOB [ 55 – 57 , 65 ], NANOS2 [ 55 , 61 ], ODF1 [ 55 ], PRDM9 [ 61 , 66 , 67 ], PRSS37 [ 55 ], RAD21L1 [ 68 ], RBMXL2 [ 55 , 62 ], RNF17 [ 69 ], SOHLH2 [ 61 , 70 ], SPACA1 [ 55 ], SPATA16 [ 55 , 56 ], SPEM1 [ 55 ], SPO11 [ 55 , 58 , 61 ], SUN5 [ 55 – 57 ], SYCP1 [ 55 ], TEX38 [ 55 ], TNP2 [ 55 ], TSSK1B [ 62 ], and ZPBP [ 55 ]—are currently associated with mutations underlying human male infertility, confirming a similar functional requirement for these genes in humans may exist. For the remaining 45 genes, however, either these genes are not required for human male fertility as they are required in mice, or associated mutations in male infertile patients have not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Section: Drug Target Specificity Of Novel Targetsmentioning

confidence: 99%

See 1 more Smart Citation

Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets

et al. 2020

View full text Add to dashboard Cite

Background: The development of a safe, effective, reversible, non-hormonal contraceptive method for men has been an ongoing effort for the past few decades. However, despite significant progress on elucidating the function of key proteins involved in reproduction, understanding male reproductive physiology is limited by incomplete information on the genes expressed in reproductive tissues, and no contraceptive targets have so far reached clinical trials. To advance product development, further identification of novel reproductive tract-specific genes leading to potentially druggable protein targets is imperative. Results: In this study, we expand on previous single tissue, single species studies by integrating analysis of publicly available human and mouse RNA-seq datasets whose initial published purpose was not focused on identifying male reproductive tract-specific targets. We also incorporate analysis of additional newly acquired human and mouse testis and epididymis samples to increase the number of targets identified. We detected a combined total of 1178 genes for which no previous evidence of male reproductive tract-specific expression was annotated, many of which are potentially druggable targets. Through RT-PCR, we confirmed the reproductive tract-specific expression of 51 novel orthologous human and mouse genes without a reported mouse model. Of these, we ablated four epididymis-specific genes (Spint3, Spint4, Spint5, and Ces5a) and two testis-specific genes (Pp2d1 and Saxo1) in individual or double knockout mice generated through the CRISPR/Cas9 system. Our results validate a functional requirement for Spint4/5 and Ces5a in male mouse fertility, while demonstrating that Spint3, Pp2d1, and Saxo1 are each individually dispensable for male mouse fertility. Conclusions: Our work provides a plethora of novel testis-and epididymis-specific genes and elucidates the functional requirement of several of these genes, which is essential towards understanding the etiology of male infertility and the development of male contraceptives.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Drug Target Specificity Of Novel Targetsmentioning

confidence: 99%

Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Nevertheless, about 2000 genes have been proposed to be directly involved in the spermatogenic process, with more than 600 of them showing a specific expression in male germ cells [19,[219][220][221]. This fact makes it extremely difficult to visualize the overall molecular picture of azoospermia, leading some authors to be skeptical about the feasibility of translating molecular genetic insights into clinical practice, especially those related to common variations of the human genome [10,222,223].…”

Section: Clinical Relevance Of the Genetic Studies Of Nonobstructive mentioning

confidence: 99%

Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic

Cerván-Martín

Castilla

Palomino-Morales

et al. 2020

JCM

View full text Add to dashboard Cite

Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, different genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men. However, these alterations only explain around 25% of azoospermic cases, with the remaining patients showing an idiopathic origin. Recent studies clearly suggest that the so-called idiopathic NOA has a complex aetiology with a polygenic inheritance, which may alter the spermatogenic process. Although we are far from a complete understanding of the molecular mechanisms underlying NOA, the use of the new technologies for genetic analysis has enabled a considerable increase in knowledge during the last years. In this review, we will provide a comprehensive and updated overview of the genetic basis of NOA, with a special focus on the possible application of the recent insights in clinical practice.

show abstract

“…Етіологія, яка лежить в основі різних підтипів НА -порушення гормонального фону, що має місце при таких патологіях, як гіпофізарна недостатність, гіперпролактинемія, гіпо-і гіпертиреоз [2]. Деякі автори вважають, що НА виникає внаслідок мікроделеції Y-хромосоми [3].…”

unclassified

Hormonal Status and Sperm Parameters in Patients with Microsurgery for Non-Obstructive Azoospermia

Панасовський¹

2020

Ukr. ž. med. bìol. sportu

View full text Add to dashboard Cite

Azoospermia occurs in approximately 10% of men with infertility and can occur due to obstruction of the reproductive tract (obstructive azoospermia) or lack of sperm production. Assessing the hormonal status of men can provide prognostic information on the effectiveness of surgical sperm removal for their further use in assisted reproductive technology programs. Before performing a testicular biopsy to establish a histological diagnosis and search for sperm in patients with non-obstructive azoospermia, it is advisable to assess the chances of obtaining sperm. The purpose of the study was to assess hormonal levels and sperm parameters during microsurgery in men with non-obstructive azoospermia. Material and methods. We analyzed the medical records of 45 men with non-obstructive azoospermia who underwent micro-TESE in the period from 2016 to 2019. We noted the data on the age of patients, their hormonal profile (level of follicle-stimulating hormone, luteinizing hormone and testosterone) were analyzed and morphofunctional characteristics of the obtained spermatozoa. Results and discussion. In our study, testosterone levels were significantly higher in patients in group 1, which may be due to the fact that men in this group were significantly younger. Sperm were removed from 10 (22%) patients with non-obstructive azoospermia. The probability of sperm removal decreased with increasing age of patients. The average concentration of sperm in the samples was (2.3±0.8) million, of which active (18.0±0.3)%. Morphological analysis of sperm revealed that the frequency of abnormalities of the head was 19.9±2.45, neck – 13.69±1.49, tail – (5.96±1.52)%. Mixed pathology, which involved defects of the head, neck and middle part were at the level of (34.6±4.21)%. The frequency of sperm neck abnormalities was (13.7±1.5)%. The most numerous were abnormalities associated with the presence of cytoplasmic residues on the surface of the sperm. The number of sperm with tail pathology was at the level of (5.9±1.5)%. In general, the mixed pathology, in which defects of the head, neck and middle part were involved, was at the level of (34.6±4.2)%. Conclusion. In this study, the frequency of positive micro-TESE, i.e. surgical procedures after which sperm were removed, was 22.2%. Morphological analysis of the drugs revealed that among the identified pathologies, most of them were sperm with the presence of one large or several small vacuoles. The number of vacuoles, their size and shape reflect defects at the level of compaction of the sperm nucleus. It has been shown that embryos formed after fertilization of oocytes with such sperm do not undergo reproductive selection and can stop in the early stages of development

show abstract

Genetic defects in human azoospermia

Cited by 49 publications

References 185 publications

Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets

Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets

Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic

Hormonal Status and Sperm Parameters in Patients with Microsurgery for Non-Obstructive Azoospermia

Contact Info

Product

Resources

About