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Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis

(2018) HUMAN REPRODUCTION. 33(2). p.258-269
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Abstract
What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis? PIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during development and adulthood. PIWILs showed a mutually exclusive pattern of subcellular localization. PIWILs were present in the intermitochondrial cement and a single large granule in meiotic GC and their expression was different from that observed in mice, highlighting species-differences. In mice, PIWIL proteins play prominent roles in male infertility. PIWIL mouse mutants show either post-meiotic arrest at the round spermatid stage (PIWIL1) or arrest at the zygotene-pachytene stage of meiosis I (PIWIL2 and PIWIL4) in males, while females remain fertile. Recent studies have reported a robust piRNA pool in human fetal ovary. PIWILsSTUDY DESIGN, SIZE, DURATION: This is a qualitative analysis of PIWILs expression in paraffin- embedded fetal human male (N = 8), female gonads (N = 6) and adult testes (N = 5), and bioinformatics analysis of online available single- cell transcriptomics data of human fetal germ cells (n = 242). Human fetal gonads from elective abortion without medical indication and adult testes biopsies were donated for research with informed consent. Samples were fixed, paraffin-embedded and analyzed by immunofluorescence to study the temporal and cellular localization of PIWIL1, PIWIL2, PIWIL3 and PIWIL4. PIWIL1, PIWIL2 and PIWIL4 showed a mutually exclusive pattern of subcellular localization, particularly in female oocytes. To our surprise, PIWIL1 immunostaining revealed the presence of a single dense paranuclear body, resembling the chromatoid body of haploid spermatocytes, in meiotic oocytes. Moreover, in contrast to mice, PIWIL4, but not PIWIL2, localized to the intermitochondrial cement. PIWIL3 was not expressed in GC during development. The upregulation of PIWIL transcripts correlated with the transcription of markers associated with piRNAs biogenesis like the TDRDs and HENMT1 in fetal GC. Non-applicable. This study is limited by the restricted number of samples and consequently stages analyzed. In the germline, PIWILs ensure the integrity of the human genome protecting it from 'parasitic sequences'. This study offers novel insights on the expression dynamics of PIWILs during the window of epigenetic remodeling and meiosis, and highlights important differences between humans and mice, which may prove particularly important to understand causes of infertility and improve both diagnosis and treatment in humans. M.G.F. was funded by Fundao para a Cincia e Tecnologia (FCT) [SFRH/BD/78689/2011]; N.H. by China Scholarship Council (CSC) [No. 201307040026] and F.W. by Medical Personnel Training Abroad Project of Henan Province [No. 2015022] and S.M.C.d.S.L. by the Netherlands Organization of Scientific Research (NWO) [ASPASIA 015.007.037] and the Interuniversity Attraction Poles-Phase VII [IUAP/PAI P7/14]. The authors have no conflicts of interest to declare.
Keywords
INTERACTING RNA PATHWAY, PIRNA PATHWAY, STEM-CELLS, GENETIC-VARIANTS, CHROMATOID BODY, MOUSE MAELSTROM, PROTEINS, OOCYTES, NUAGE, MIWI, PIWIL, human, intermitochondrial cement, gametogenesis, meiosis, oocyte, chromatoid body, subcellular localization, spermatogenesis, development

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MLA
Fernandes, Maria Gomes, et al. “Human-Specific Subcellular Compartmentalization of P-Element Induced Wimpy Testis-like (PIWIL) Granules during Germ Cell Development and Spermatogenesis.” HUMAN REPRODUCTION, vol. 33, no. 2, 2018, pp. 258–69, doi:10.1093/humrep/dex365.
APA
Fernandes, M. G., He, N., Wang, F., Van Iperen, L., Eguizabal, C., Matorras, R., … Chuva de Sousa Lopes, S. M. (2018). Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis. HUMAN REPRODUCTION, 33(2), 258–269. https://doi.org/10.1093/humrep/dex365
Chicago author-date
Fernandes, Maria Gomes, Nannan He, Fang Wang, Liesbeth Van Iperen, Cristina Eguizabal, Roberto Matorras, Bernard AJ Roelen, and Susana Marina Chuva de Sousa Lopes. 2018. “Human-Specific Subcellular Compartmentalization of P-Element Induced Wimpy Testis-like (PIWIL) Granules during Germ Cell Development and Spermatogenesis.” HUMAN REPRODUCTION 33 (2): 258–69. https://doi.org/10.1093/humrep/dex365.
Chicago author-date (all authors)
Fernandes, Maria Gomes, Nannan He, Fang Wang, Liesbeth Van Iperen, Cristina Eguizabal, Roberto Matorras, Bernard AJ Roelen, and Susana Marina Chuva de Sousa Lopes. 2018. “Human-Specific Subcellular Compartmentalization of P-Element Induced Wimpy Testis-like (PIWIL) Granules during Germ Cell Development and Spermatogenesis.” HUMAN REPRODUCTION 33 (2): 258–269. doi:10.1093/humrep/dex365.
Vancouver
1.
Fernandes MG, He N, Wang F, Van Iperen L, Eguizabal C, Matorras R, et al. Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis. HUMAN REPRODUCTION. 2018;33(2):258–69.
IEEE
[1]
M. G. Fernandes et al., “Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis,” HUMAN REPRODUCTION, vol. 33, no. 2, pp. 258–269, 2018.
@article{8615361,
  abstract     = {{What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis? 
PIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during development and adulthood. PIWILs showed a mutually exclusive pattern of subcellular localization. PIWILs were present in the intermitochondrial cement and a single large granule in meiotic GC and their expression was different from that observed in mice, highlighting species-differences. 
In mice, PIWIL proteins play prominent roles in male infertility. PIWIL mouse mutants show either post-meiotic arrest at the round spermatid stage (PIWIL1) or arrest at the zygotene-pachytene stage of meiosis I (PIWIL2 and PIWIL4) in males, while females remain fertile. Recent studies have reported a robust piRNA pool in human fetal ovary. 
PIWILsSTUDY DESIGN, SIZE, DURATION: This is a qualitative analysis of PIWILs expression in paraffin- embedded fetal human male (N = 8), female gonads (N = 6) and adult testes (N = 5), and bioinformatics analysis of online available single- cell transcriptomics data of human fetal germ cells (n = 242). 
Human fetal gonads from elective abortion without medical indication and adult testes biopsies were donated for research with informed consent. Samples were fixed, paraffin-embedded and analyzed by immunofluorescence to study the temporal and cellular localization of PIWIL1, PIWIL2, PIWIL3 and PIWIL4. 
PIWIL1, PIWIL2 and PIWIL4 showed a mutually exclusive pattern of subcellular localization, particularly in female oocytes. To our surprise, PIWIL1 immunostaining revealed the presence of a single dense paranuclear body, resembling the chromatoid body of haploid spermatocytes, in meiotic oocytes. Moreover, in contrast to mice, PIWIL4, but not PIWIL2, localized to the intermitochondrial cement. PIWIL3 was not expressed in GC during development. The upregulation of PIWIL transcripts correlated with the transcription of markers associated with piRNAs biogenesis like the TDRDs and HENMT1 in fetal GC. 
Non-applicable. 
This study is limited by the restricted number of samples and consequently stages analyzed. 
In the germline, PIWILs ensure the integrity of the human genome protecting it from 'parasitic sequences'. This study offers novel insights on the expression dynamics of PIWILs during the window of epigenetic remodeling and meiosis, and highlights important differences between humans and mice, which may prove particularly important to understand causes of infertility and improve both diagnosis and treatment in humans. 
M.G.F. was funded by Fundao para a Cincia e Tecnologia (FCT) [SFRH/BD/78689/2011]; N.H. by China Scholarship Council (CSC) [No. 201307040026] and F.W. by Medical Personnel Training Abroad Project of Henan Province [No. 2015022] and S.M.C.d.S.L. by the Netherlands Organization of Scientific Research (NWO) [ASPASIA 015.007.037] and the Interuniversity Attraction Poles-Phase VII [IUAP/PAI P7/14]. The authors have no conflicts of interest to declare.}},
  author       = {{Fernandes, Maria Gomes and He, Nannan and Wang, Fang and Van Iperen, Liesbeth and Eguizabal, Cristina and Matorras, Roberto and Roelen, Bernard AJ and Chuva de Sousa Lopes, Susana Marina}},
  issn         = {{0268-1161}},
  journal      = {{HUMAN REPRODUCTION}},
  keywords     = {{INTERACTING RNA PATHWAY,PIRNA PATHWAY,STEM-CELLS,GENETIC-VARIANTS,CHROMATOID BODY,MOUSE MAELSTROM,PROTEINS,OOCYTES,NUAGE,MIWI,PIWIL,human,intermitochondrial cement,gametogenesis,meiosis,oocyte,chromatoid body,subcellular localization,spermatogenesis,development}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{258--269}},
  title        = {{Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis}},
  url          = {{http://doi.org/10.1093/humrep/dex365}},
  volume       = {{33}},
  year         = {{2018}},
}

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