Spermatogenesis is normal in <i>Tex33</i> knockout mice

Zhu, Zhendong; Zhang, Xin; Zeng, Wentao; Zhao, Shuqin; Zhou, Jianli; Zhou, Zuomin; Liu, Mingxi

doi:10.7717/peerj.9629

Cited by 11 publications

(9 citation statements)

References 39 publications

(43 reference statements)

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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%

“…Infertility is a global human health concern and affects approximately 8%–12% of couples around the world 1 , 2 . Male infertility, which accounts for half of all infertility cases, is generally manifested by reduced sperm count (oligozoospermia and azoospermia), reduced sperm motility (asthenozoospermia), or increased percentage of abnormal sperm morphology (teratozoospermia).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…Tex33 expression is testis-specific; the encoded protein is found in the cytoplasm of round spermatids but much less in elongated spermatids [ 48 ]. Given that spermatogenesis is normal in male tex33 -null mice, Tex33 might not be essential [ 49 ].…”

Section: Tex Gene Expression and Function In The Mousementioning

confidence: 99%

“…Sperm physiology and motility are abnormal, which impair sperm migration into the oviduct and hinder the acrosome reaction. TEX101 is therefore essential for male fertility; it has been suggested that TEX101 operates as a cell surface chaperone involved in the maturation of proteins required for sperm migration and sperm-oocyte interaction (such as Adam3) [49][50][51][52][54][55][56][57].…”

Section: Tex101mentioning

confidence: 99%

Human testis-expressed (TEX) genes: a review focused on spermatogenesis and male fertility

Bellil

Ghieh

Hermel

et al. 2021

Basic Clin. Androl.

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Spermatogenesis is a complex process regulated by a multitude of genes. The identification and characterization of male-germ-cell-specific genes is crucial to understanding the mechanisms through which the cells develop. The term “TEX gene” was coined by Wang et al. (Nat Genet. 2001; 27: 422–6) after they used cDNA suppression subtractive hybridization (SSH) to identify new transcripts that were present only in purified mouse spermatogonia. TEX (Testis expressed) orthologues have been found in other vertebrates (mammals, birds, and reptiles), invertebrates, and yeasts. To date, 69 TEX genes have been described in different species and different tissues. To evaluate the expression of each TEX/tex gene, we compiled data from 7 different RNA-Seq mRNA databases in humans, and 4 in the mouse according to the expression atlas database.Various studies have highlighted a role for many of these genes in spermatogenesis. Here, we review current knowledge on the TEX genes and their roles in spermatogenesis and fertilization in humans and, comparatively, in other species (notably the mouse). As expected, TEX genes appear to have a major role in reproduction in general and in spermatogenesis in humans but also in all mammals such as the mouse. Most of them are expressed specifically or predominantly in the testis. As most of the TEX genes are highly conserved in mammals, defects in the male (gene mutations in humans and gene-null mice) lead to infertility. In the future, cumulative data on the human TEX genes’ physiological functions and pathophysiological dysfunctions should become available and is likely to confirm the essential role of this family in the reproductive process. Thirteen TEX genes are now referenced in the OMIM database, and 3 have been linked to a specific phenotype. TEX11 (on Xq13.1) is currently the gene most frequently reported as being associated with azoospermia.

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“…For example: T-complex-associated-testis-expressed 1 (TCTE1) is an important axonemal protein that is required for sperm motility (5); F-box protein 47 (FBXO47) is localized specifically in spermatocytes and directs integration between the telomere and inner nuclear envelope during meiotic progression (6); MRN complex interacting protein (MRNIP) is a MRN-interacting protein essential for chromosome synapsis and meiotic homologous recombination (7). On the other hand, we have also shown that several genes [Retinoic acid induced 14 (Rai14), testis expressed 33 (Tex33), Fibronectin type 3 and ankyrin repeat domains 1 (Fank1), and Eukaryotic elongation factor-2 kinase (Eef2k)], previously postulated as crucial factors for spermatogenesis, are dispensable for spermatogenesis and male fertility (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Testis-enriched Asb12 is not required for spermatogenesis and fertility in mice

Zhang¹,

Xu²,

Shen³

et al. 2022

Transl Androl Urol

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Background: Members of the ankyrin repeat and SOCS box (Asb) family are expressed abundantly in testes. Some Asb genes/proteins are required for spermatogenesis, but the function of Asb12 during spermatogenesis is not clear. We investigated the physiological role of Asb12 in murine testes. Methods:The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system was used to generate Asb12-knockout (KO) mice. Histology and immunostaining were done to assess the effects of Asb12 KO on mouse testes and epididymides. Semen quality was analyzed using a computerassisted sperm analyzer. The terminal deoxynucleotidyl transferase-dUTP nick-end labeling assay was employed to examine testicular apoptosis. Real-time reverse transcription-quantitative polymerase chain reaction (PCR) was conducted to calculate gene transcription levels.Results: Asb12 was expressed predominantly in murine testes. Immunostaining of Asb12 protein revealed that Asb12 was located specifically in the acrosome of elongated spermatids, which suggested a potential role of Asb12 during spermatogenesis. However, Asb12-KO mice had normal fertility, and no overt difference was detected in testicular morphology, semen quality, or apoptosis when comparing Asb12-KO and Asb12-wild type (WT) mice. Gene expression of several Asb family members was increased significantly in the testes of Asb12-KO mice when compared with that in Asb12-WT mice, which suggested functional compensation from paralogs for Asb12 loss. Conclusions:We demonstrated that Asb12 is not essential for the spermatogenesis and fertility of mice.Our findings will assist researchers in avoiding redundant efforts, and provide a baseline resource for genetic studies on human fertility.

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Spermatogenesis is normal in Tex33 knockout mice

Cited by 11 publications

References 39 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

Human testis-expressed (TEX) genes: a review focused on spermatogenesis and male fertility

Testis-enriched Asb12 is not required for spermatogenesis and fertility in mice

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