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Mouse Y-Encoded Transcription Factor Zfy2 Is Essential for Sperm Formation and Function in Assisted Fertilization.

Yamauchi Y, Riel JM, Ruthig V, Ward MA - PLoS Genet. (2015)

Bottom Line: Spermatogenesis is a key developmental process allowing for a formation of a mature male gamete.During its final phase, spermiogenesis, haploid round spermatids undergo cellular differentiation into spermatozoa, which involves extensive restructuring of cell morphology, DNA, and epigenome.Therefore, only three Y chromosome genes, Sry, Eif2s3y and Zfy2, constitute the minimum Y chromosome complement compatible with successful intracytoplasmic sperm injection in the mouse.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.

ABSTRACT
Spermatogenesis is a key developmental process allowing for a formation of a mature male gamete. During its final phase, spermiogenesis, haploid round spermatids undergo cellular differentiation into spermatozoa, which involves extensive restructuring of cell morphology, DNA, and epigenome. Using mouse models with abrogated Y chromosome gene complements and Y-derived transgene we identified Y chromosome encoded Zfy2 as the gene responsible for sperm formation and function. In the presence of a Zfy2 transgene, mice lacking the Y chromosome and transgenic for two other Y-derived genes, Sry driving sex determination and Eif2s3y initiating spermatogenesis, are capable of producing sperm which when injected into the oocytes yield live offspring. Therefore, only three Y chromosome genes, Sry, Eif2s3y and Zfy2, constitute the minimum Y chromosome complement compatible with successful intracytoplasmic sperm injection in the mouse.

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Histology analysis.(A) Exemplary tubules of stage VII-VIII testis sections. XEY*XSry males have meiotic and post-meiotic arrest that only occasionally allow formation of round spermatids that do not develop beyond step 7 of spermatid development. In XESxrbY*X spermatid elongation is observed but usually ceases at step 11–12, with few occurrences of more advanced stages. In XE,Z2Y*XSry males spermatogenesis is progressing with good spermatid elongation and many spermatids developing to step 15–16; these elongated spermatids are morphologically abnormal, which is expected from males lacking NPYq genes [19]. Tubule stages are shown in Roman numerals and steps of spermatid development (St) in Arabic numerals. Bar = 50 μm; insets = x3 magnification. See also S3 Fig emphasizing spermatid at step 7–8. (B) Quantitative analysis of spermatogenesis progression. For each male 10 tubules were examined per stage and the numbers of round spermatid (steps 1–8), elongating/ed spermatid (steps 9–16), and Sertoli cells were counted. The data are expressed as spermatid/Sertoli cell ratios. In wild-type males no round spermatids are present in stages IX-XI so those observed in males with limited Y gene complement represent 'delayed spermatids'. Statistical significance (t-test): a different than XEY*XSry; b different than XESxrbY*X; c different than all other. Three males per genotypes were included in the analysis. For explanation of male genotypes see Fig 1, S1 Table, and text.
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pgen.1005476.g002: Histology analysis.(A) Exemplary tubules of stage VII-VIII testis sections. XEY*XSry males have meiotic and post-meiotic arrest that only occasionally allow formation of round spermatids that do not develop beyond step 7 of spermatid development. In XESxrbY*X spermatid elongation is observed but usually ceases at step 11–12, with few occurrences of more advanced stages. In XE,Z2Y*XSry males spermatogenesis is progressing with good spermatid elongation and many spermatids developing to step 15–16; these elongated spermatids are morphologically abnormal, which is expected from males lacking NPYq genes [19]. Tubule stages are shown in Roman numerals and steps of spermatid development (St) in Arabic numerals. Bar = 50 μm; insets = x3 magnification. See also S3 Fig emphasizing spermatid at step 7–8. (B) Quantitative analysis of spermatogenesis progression. For each male 10 tubules were examined per stage and the numbers of round spermatid (steps 1–8), elongating/ed spermatid (steps 9–16), and Sertoli cells were counted. The data are expressed as spermatid/Sertoli cell ratios. In wild-type males no round spermatids are present in stages IX-XI so those observed in males with limited Y gene complement represent 'delayed spermatids'. Statistical significance (t-test): a different than XEY*XSry; b different than XESxrbY*X; c different than all other. Three males per genotypes were included in the analysis. For explanation of male genotypes see Fig 1, S1 Table, and text.

Mentions: To assess Zfy2 role in spermatogenesis progression we investigated testis histology in XEY*XSry males transgenic for Zfy2 (Fig 2 and S3 Fig). These males are subsequently called XE,Z2Y*XSry (Fig 1B, S1 Table). While in XEY*XSry males spermatid development did not progress beyond the round spermatid stage, in XE,Z2Y*XSry males spermatids elongated (Fig 2A). The elongated, condensed spermatids were more frequently observed in XE,Z2Y*XSry than in XESxrbY*X males; in the latter genotype elongation often ceased earlier (at step 12–13) and the spermatid nuclei were less compacted, with lighter staining pattern. Quantitative analysis of spermatogenesis progression (Fig 2B) demonstrated that XE,Z2Y*XSry had more round spermatids than XEY*XSry (~2.8-fold increase), reaching a level similar to that observed with XESxrbY*X males, but less than in wild-type controls. The number of elongating/elongated spermatids in XE,Z2Y*XSry and XESxrbY*X was not significantly different, and ~10-fold lower than in wild-type controls. In the quantitative analysis of testis sections we did not distinguish between the elongating and elongated spermatids because the abnormal morphology of developing spermatids, which ultimately resulted in severely morphologically abnormal headshape of testicular and epididymal sperm, made such distinction impossible.


Mouse Y-Encoded Transcription Factor Zfy2 Is Essential for Sperm Formation and Function in Assisted Fertilization.

Yamauchi Y, Riel JM, Ruthig V, Ward MA - PLoS Genet. (2015)

Histology analysis.(A) Exemplary tubules of stage VII-VIII testis sections. XEY*XSry males have meiotic and post-meiotic arrest that only occasionally allow formation of round spermatids that do not develop beyond step 7 of spermatid development. In XESxrbY*X spermatid elongation is observed but usually ceases at step 11–12, with few occurrences of more advanced stages. In XE,Z2Y*XSry males spermatogenesis is progressing with good spermatid elongation and many spermatids developing to step 15–16; these elongated spermatids are morphologically abnormal, which is expected from males lacking NPYq genes [19]. Tubule stages are shown in Roman numerals and steps of spermatid development (St) in Arabic numerals. Bar = 50 μm; insets = x3 magnification. See also S3 Fig emphasizing spermatid at step 7–8. (B) Quantitative analysis of spermatogenesis progression. For each male 10 tubules were examined per stage and the numbers of round spermatid (steps 1–8), elongating/ed spermatid (steps 9–16), and Sertoli cells were counted. The data are expressed as spermatid/Sertoli cell ratios. In wild-type males no round spermatids are present in stages IX-XI so those observed in males with limited Y gene complement represent 'delayed spermatids'. Statistical significance (t-test): a different than XEY*XSry; b different than XESxrbY*X; c different than all other. Three males per genotypes were included in the analysis. For explanation of male genotypes see Fig 1, S1 Table, and text.
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Related In: Results  -  Collection

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pgen.1005476.g002: Histology analysis.(A) Exemplary tubules of stage VII-VIII testis sections. XEY*XSry males have meiotic and post-meiotic arrest that only occasionally allow formation of round spermatids that do not develop beyond step 7 of spermatid development. In XESxrbY*X spermatid elongation is observed but usually ceases at step 11–12, with few occurrences of more advanced stages. In XE,Z2Y*XSry males spermatogenesis is progressing with good spermatid elongation and many spermatids developing to step 15–16; these elongated spermatids are morphologically abnormal, which is expected from males lacking NPYq genes [19]. Tubule stages are shown in Roman numerals and steps of spermatid development (St) in Arabic numerals. Bar = 50 μm; insets = x3 magnification. See also S3 Fig emphasizing spermatid at step 7–8. (B) Quantitative analysis of spermatogenesis progression. For each male 10 tubules were examined per stage and the numbers of round spermatid (steps 1–8), elongating/ed spermatid (steps 9–16), and Sertoli cells were counted. The data are expressed as spermatid/Sertoli cell ratios. In wild-type males no round spermatids are present in stages IX-XI so those observed in males with limited Y gene complement represent 'delayed spermatids'. Statistical significance (t-test): a different than XEY*XSry; b different than XESxrbY*X; c different than all other. Three males per genotypes were included in the analysis. For explanation of male genotypes see Fig 1, S1 Table, and text.
Mentions: To assess Zfy2 role in spermatogenesis progression we investigated testis histology in XEY*XSry males transgenic for Zfy2 (Fig 2 and S3 Fig). These males are subsequently called XE,Z2Y*XSry (Fig 1B, S1 Table). While in XEY*XSry males spermatid development did not progress beyond the round spermatid stage, in XE,Z2Y*XSry males spermatids elongated (Fig 2A). The elongated, condensed spermatids were more frequently observed in XE,Z2Y*XSry than in XESxrbY*X males; in the latter genotype elongation often ceased earlier (at step 12–13) and the spermatid nuclei were less compacted, with lighter staining pattern. Quantitative analysis of spermatogenesis progression (Fig 2B) demonstrated that XE,Z2Y*XSry had more round spermatids than XEY*XSry (~2.8-fold increase), reaching a level similar to that observed with XESxrbY*X males, but less than in wild-type controls. The number of elongating/elongated spermatids in XE,Z2Y*XSry and XESxrbY*X was not significantly different, and ~10-fold lower than in wild-type controls. In the quantitative analysis of testis sections we did not distinguish between the elongating and elongated spermatids because the abnormal morphology of developing spermatids, which ultimately resulted in severely morphologically abnormal headshape of testicular and epididymal sperm, made such distinction impossible.

Bottom Line: Spermatogenesis is a key developmental process allowing for a formation of a mature male gamete.During its final phase, spermiogenesis, haploid round spermatids undergo cellular differentiation into spermatozoa, which involves extensive restructuring of cell morphology, DNA, and epigenome.Therefore, only three Y chromosome genes, Sry, Eif2s3y and Zfy2, constitute the minimum Y chromosome complement compatible with successful intracytoplasmic sperm injection in the mouse.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.

ABSTRACT
Spermatogenesis is a key developmental process allowing for a formation of a mature male gamete. During its final phase, spermiogenesis, haploid round spermatids undergo cellular differentiation into spermatozoa, which involves extensive restructuring of cell morphology, DNA, and epigenome. Using mouse models with abrogated Y chromosome gene complements and Y-derived transgene we identified Y chromosome encoded Zfy2 as the gene responsible for sperm formation and function. In the presence of a Zfy2 transgene, mice lacking the Y chromosome and transgenic for two other Y-derived genes, Sry driving sex determination and Eif2s3y initiating spermatogenesis, are capable of producing sperm which when injected into the oocytes yield live offspring. Therefore, only three Y chromosome genes, Sry, Eif2s3y and Zfy2, constitute the minimum Y chromosome complement compatible with successful intracytoplasmic sperm injection in the mouse.

Show MeSH
Related in: MedlinePlus