The ubiquitin specific protease 26 (USP26) gene is located at Xq26.2 and present as a single exon on the X chromosome encoding for a protein of 913 amino acids. It belongs to a large family of deubiquitinating enzymes, and is exclusively expressed in the testis. There are conflicting reports on whether mutations in USP26 are associated with male infertility. This article updates the researches on the USP26 gene, its complicated relationship with male spermatogenesis dysfunction, the role of its mutation in male infertility, its geographical or ethnic distribution, and its evolution.
Cysteine Endopeptidases ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Spermatogenesis ; genetics

Male infertility is a common complex disease. Y-linked spermatogenic failure is an important cause for this disorder. Due to the presence of many repeat sequences and the frequent occurrence of non-allelic homologous recombination between the sequences in the male-specific region of the Y (MSY) region of the chromosome, Y chromosome possesses high variation rate. The variations may result in the dosage changes of spermatogenesis-related gene families and lead to male infertility. The present article reviews the recent progress of the study on Y chromosome variations, and its possible effect on spermatogenic function, in DNA level.
Chromosomes, Human, Y ; genetics ; Haplotypes ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Mutation ; Spermatogenesis ; genetics

In this study we investigate the expression pattern of mucin genes in the human testis and evaluate the relationship between the expression of mucin genes and impaired spermatogenesis in the human testis. Thirty human testis tissues were collected from patients undergoing diagnostic testicular biopsy to investigate the cause of infertility. One part of the tissue underwent histological observation, and the other part of the tissue was subjected to semiquantitative RT-PCR of mucin genes, that is, mucin1, 2, 3, 4, and 9. The relative amount of mucin mRNAs was calculated by densitometry using glyceraldehydes-3-phosphate dehydrogenase (GAPDH) as an internal control. The samples were histologically diagnosed as either obstructive azoospermia with normal spermatogenesis (n = 13) or non-obstructive azoospermia with impaired spermatogenesis (n = 17). In the human testis with normal spermatogenesis, mRNA expression of mucin1, 9, 13 and GAPDH were found, but RT-PCR products of mucin 2, 3 and 4 were not detected. In the testis with impaired spermatogenesis, however, RT-PCR product of mucin1 was not found. There was no difference in the other mucin mRNA expression patterns between the testis with either normal or impaired spermatogenesis. To our knowledge, this study is the first that has detected the mRNA of mucin9 and 13 in human testis. This study also shows that mucin1 expression might be closely related to spermatogenesis. Our findings should be substantiated by more direct evidence, such as mucin protein expression and localization.
Testis/*metabolism ; *Spermatogenesis ; Mucins/*genetics ; Middle Aged ; Male ; Humans ; Glycoproteins/genetics ; Antigens, Neoplasm ; Antigens/genetics ; Adult

Eukaryotes produce various types of 19-30 nt small RNAs, which act as guides to the regulation of gene expressions, such as mRNA degradation and translational repression. The Argonaute family members related to small RNA functions fall into 2 subfamilies. One is the AGO subfamily, whose 4 members distribute widely, confirmedly bind to miRNAs and siRNAs and inhibit the expression of target mRNAs through a pathway like RNA interference. The other is the PIWI subfamily, including PIWI, Aubgine (AUB) and AGO3, exclusively expressed in the testis. Recently, four research groups have isolated a new class of small RNAs from the mammalian testis, which interacts with the PIWI subfamily, hence named piwi-interfering RNAs (piRNAs), and is suggestive of an important role in spermatogenesis.
Animals ; Male ; MicroRNAs ; classification ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics ; Spermatogenesis ; genetics ; Testis ; metabolism

Failure of spermatogenesis is the main clinical manifestation of male infertility. Multiple factors including genetic factors may affect spermatogenesis. Azoopermia factor (AZF) is closely involved in spermatogenesis. This paper reviews recent progress made in the study of AZF and its role in spermatogenesis and male infertility.
Azoospermia ; etiology ; genetics ; Humans ; Infertility, Male ; etiology ; genetics ; Male ; Spermatogenesis ; genetics

The Y chromosome contains genes closely related to male gonadal development and spermatogenesis. The azoospermia factor (AZF) is a gene on the long arm of the Y chromosome that regulates spermatogenesis, and its deletion can induce spermatogenic arrest and consequently male infertility. Most researchers subdivide AZF into AZFa, AZFb and AZFc, and some believe there to be another region, AZFd, between AZFa and AZFb. Different AZF deletions lead to different phenotypes. AZFc deletion, as the commonest type that attracts widespread attention of researchers, includes complete AZF deletion and partial AZF deletion, and the latter mainly consists of gr/gr deletion and b2/b3 deletion. The gr/gr deletion can cause infertility in some areas or in human species. The influence of b2/b3 deletion on spermatogenesis has not been confirmed, but its wide spread in haplogroup N has distribution scientists' attention. This review outlines the structures, candidate genes and deletions of AZF, especially AZFc, along with their relationship with spermatogenesis, so as to provide a theoretical basis for clinical prenatal diagnosis and treatment of infertility.
Azoospermia ; etiology ; genetics ; Chromosomes, Human, Y ; Gene Deletion ; Humans ; Infertility, Male ; etiology ; genetics ; Male ; Spermatogenesis ; genetics

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.
Centrioles/genetics* ; Homozygote ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Spermatogenesis/genetics* ; Spermatozoa

Animals ; CRISPR-Cas Systems/genetics* ; Fertility/genetics* ; Gene Editing ; Male ; Mice ; Spermatogenesis/genetics* ; Testis

Adult ; Cell Cycle Proteins/genetics* ; Codon, Nonsense/genetics* ; Consanguinity ; Humans ; Infertility, Male/genetics* ; Male ; Oligospermia/genetics* ; Pedigree ; Spermatogenesis/genetics*

The gene approach to the pathogenesis of male infertility may bring about some strategies for the diagnosis and manage of the condition. Gene knockout technology is the mainstream method currently used in the study of gene function. Screening and identification of testis-specific genes and insights into their features and functions in spermatogenesis are significant for a further understanding of testicular functions and searching for new therapeutic targets for male reproductive disorders. This review focuses on the application of gene knockout technology in the study of spermatogenesis-associated genes.
Animals ; Gene Knockout Techniques ; Humans ; Infertility, Male ; genetics ; Male ; Spermatogenesis ; genetics