Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice

Busada, Jonathan T.; Velte, Ellen K.; Serra, Nicholas D; Cook, Kenneth; Niedenberger, Bryan A.; Willis, William D.; Goulding, Eugenia H.; Eddy, Edward M.; Geyer, Christopher B.

doi:10.1530/rep-16-0268

Cited by 29 publications

(17 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To determine the expression profile of Tex33 during the first wave of spermatogenesis, mouse testes were obtained at postnatal day 7 (containing only spermatogonia), day 14 (containing spermatogonia and spermatocytes), day 21 (in which round spermatids begin to appear), day 28 (in which spermatids begin to elongate), day 35 (around which time the first wave of spermatogenesis is completed) and day 56 ( 3 , 28 ). The results of RT-PCR analysis suggested that V2 was expressed weakly from day 21 in the mouse testes, peaked at day 28 and was expressed into adulthood, while V1 and V3 were expressed from day 28 and maintained peak expression levels into adulthood ( Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Testis-expressed protein 33 is not essential for spermiogenesis and fertility in mice

Xia

Niu

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

Gene expression analyses have revealed that there are >2,300 testis-enriched genes in mice, and gene knockout models have shown that a number of them are responsible for male fertility. However, the functions of numerous genes have yet to be clarified. The aim of the present study was to identify the expression pattern of testis-expressed protein 33 (TEX33) in mice and explore the role of TEX33 in male reproduction. Reverse transcription-polymerase chain reaction and western blot assays were used to investigate the mRNA and protein levels of TEX33 in mouse testes during the first wave of spermatogenesis. Immunofluorescence analysis was also performed to identify the cellular and structural localization of TEX33 protein in the testes. Tex33 knockout mice were generated by CRISPR/Cas9 gene-editing. Histological analysis with hematoxylin and eosin or periodic acid-Schiff (PAS) staining, computer-assisted sperm analysis (CASA) and fertility testing, were also carried out to evaluate the effect of TEX33 on mouse spermiogenesis and male reproduction. The results showed that Tex33 mRNA and protein were exclusively expressed in mouse testes and were first detected on postnatal days 21–28 (spermiogenesis phase); their expression then remained into adulthood. Immunofluorescence analysis revealed that TEX33 protein was located in the spermatids and sperm within the seminiferous tubules of the mouse testes, and exhibited specific localization to the acrosome, flagellum and manchette during spermiogenesis. These results suggested that TEX33 may play a role in mouse spermiogenesis. However, Tex33 knockout mice presented no detectable difference in testis-to-body weight ratios when compared with wild-type mice. PAS staining and CASA revealed that spermatogenesis and sperm quality were normal in mice lacking Tex33 . In addition, fertility testing suggested that the Tex33 knockout mice had normal reproductive functions. In summary, the findings of the present study indicate that TEX33 is associated with spermiogenesis but is not essential for sperm development and male fertility.

show abstract

Section: Resultsmentioning

confidence: 99%

“…1G ). The appearance of Tex33 transcript variants and proteins coincides with the spermiogenesis phase, during which time the appearance of round spermatids begins and spermiogenesis is initiated ( 28 ).…”

Section: Resultsmentioning

confidence: 99%

Testis-expressed protein 33 is not essential for spermiogenesis and fertility in mice

Xia

Niu

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

show abstract

“…Nevertheless, sperm production normalized at later stages of testis development, indicating that the functions of DMXL2 are essentially limited to the first wave of spermatogenesis or that compensatory processes occur after puberty. As suggested by Busada et al for Rhox13 [57], Dmxl2 expression in spermatogenic cells may be advantageous in mice, supporting early fertility by providing additional germ cells at the start of the animal’s reproductive life.…”

Section: Discussionmentioning

confidence: 99%

Dual role of DMXL2 in olfactory information transmission and the first wave of spermatogenesis

Gobe¹,

Elzaïat²,

Meunier³

et al. 2019

PLoS Genet

View full text Add to dashboard Cite

Gonad differentiation is a crucial step conditioning the future fertility of individuals and most of the master genes involved in this process have been investigated in detail. However, transcriptomic analyses of developing gonads from different animal models have revealed that hundreds of genes present sexually dimorphic expression patterns. DMXL2 was one of these genes and its function in mammalian gonads was unknown. We therefore investigated the phenotypes of total and gonad-specific Dmxl2 knockout mouse lines. The total loss-of-function of Dmxl2 was lethal in neonates, with death occurring within 12 hours of birth. Dmxl2 -knockout neonates were weak and did not feed. They also presented defects of olfactory information transmission and severe hypoglycemia, suggesting that their premature death might be due to global neuronal and/or metabolic deficiencies. Dmxl2 expression in the gonads increased after birth, during follicle formation in females and spermatogenesis in males. DMXL2 was detected in both the supporting and germinal cells of both sexes. As Dmxl2 loss-of-function was lethal, only limited investigations of the gonads of Dmxl2 KO pups were possible. They revealed no major defects at birth. The gonadal function of Dmxl2 was then assessed by conditional deletions of the gene in gonadal supporting cells, germinal cells, or both. Conditional Dmxl2 ablation in the gonads did not impair fertility in males or females. By contrast, male mice with Dmxl2 deletions, either throughout the testes or exclusively in germ cells, presented a subtle testicular phenotype during the first wave of spermatogenesis that was clearly detectable at puberty. Indeed, Dmxl2 loss-of-function throughout the testes or in germ cells only, led to sperm counts more than 60% lower than normal and defective seminiferous tubule architecture. Transcriptomic and immunohistochemichal analyses on these abnormal testes revealed a deregulation of Sertoli cell phagocytic activity related to germ cell apoptosis augmentation. In conclusion, we show that Dmxl2 exerts its principal function in the testes at the onset of puberty, although its absence does not compromise male fertility in mice.

show abstract

“…Mok and coauthors reported that mTORC1 and mTORC2 signalling complexes can regulate preleptotene spermatocyte migration across the blood testicular barrier (Mok, Mruk, Lee, & Cheng, ). mTORC1 activation is needed for spermatogonial differentiation, and its inhibition leads to suppression of spermatogonial differentiation and accumulation of undifferentiated progenitor spermatogonia (Busada et al, ). Moreover, mTOR inhibition by rapamycin or its analogue (sirolimus) in male patients may lead to vacuolisation and atrophy of seminiferous tubules, decreased sperm production and reversible infertility (Xu et al, ), while withdrawal of sirolimus improves semen parameters and sex hormone levels (Deutsch et al, ).…”

Section: Discussionmentioning

confidence: 99%

The correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele

et al. 2019

View full text Add to dashboard Cite

This study aimed to assess the possible correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele. The study included sixty infertile males and fifty fertile males as controls. The infertile group was subdivided into the following subgroups: thirty males with varicocele and thirty males without varicocele. All subjects underwent medical history collection, clinical examination, semen analysis, sperm DNA integrity assessment, mTOR gene expression assessment and scrotal colour Doppler ultrasound. The mean mTOR gene expression in infertile patients with varicocele (23.52 ± 14.65) was significantly higher than that in infertile patients without varicocele (12.24 ± 12.44) and fertile control subjects (3.92 ± 3.26; p = 0.003 and p < 0.001 respectively). In the infertile varicocele‐positive group, mTOR gene expression showed a significant negative correlation with sperm count (p = 0.028, r = −0.400) and progressive sperm motility (p = 0.038, r = −0.381), as well as a significant positive correlation with the sperm DNA fragmentation index (DFI; p = 0.001, r = 0.578). In the infertile varicocele‐negative group, mTOR gene expression showed a significant negative correlation with progressive sperm motility (p = 0.018, r = −0.429) and a significant positive correlation with sperm DFI (p < 0.001, r = 0.673). In conclusion, according to these results, there is a significant positive correlation between mTOR gene expression and sperm DFI among infertile patients with and without varicocele.

show abstract

Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice

Cited by 29 publications

References 44 publications

Testis-expressed protein 33 is not essential for spermiogenesis and fertility in mice

Testis-expressed protein 33 is not essential for spermiogenesis and fertility in mice

Dual role of DMXL2 in olfactory information transmission and the first wave of spermatogenesis

The correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele

Contact Info

Product

Resources

About