The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/134 |
Resumo: | BACKGROUND: The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction. METHODS: In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities. RESULTS: Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome. CONCLUSIONS: AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome. |
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The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertilityY chromosomeAZFcPartial AZFc deletionsSpermatogenesisMale infertilityDoenças GenéticasBACKGROUND: The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction. METHODS: In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities. RESULTS: Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome. CONCLUSIONS: AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome.Oxford University PressRepositório Científico do Instituto Nacional de SaúdeNavarro-Costa, PauloGonçalves, JoãoPlancha, Carlos E.2011-09-08T14:18:48Z2010-092010-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/134engHum Reprod Update. 2010 Sep-Oct;16(5):525-42. Epub 2010 Mar 181355-4786doi:10.1093/humupd/dmq005info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:38:01Zoai:repositorio.insa.pt:10400.18/134Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:35:20.484415Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
title |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
spellingShingle |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility Navarro-Costa, Paulo Y chromosome AZFc Partial AZFc deletions Spermatogenesis Male infertility Doenças Genéticas |
title_short |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
title_full |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
title_fullStr |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
title_full_unstemmed |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
title_sort |
The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility |
author |
Navarro-Costa, Paulo |
author_facet |
Navarro-Costa, Paulo Gonçalves, João Plancha, Carlos E. |
author_role |
author |
author2 |
Gonçalves, João Plancha, Carlos E. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Navarro-Costa, Paulo Gonçalves, João Plancha, Carlos E. |
dc.subject.por.fl_str_mv |
Y chromosome AZFc Partial AZFc deletions Spermatogenesis Male infertility Doenças Genéticas |
topic |
Y chromosome AZFc Partial AZFc deletions Spermatogenesis Male infertility Doenças Genéticas |
description |
BACKGROUND: The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction. METHODS: In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities. RESULTS: Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome. CONCLUSIONS: AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-09 2010-09-01T00:00:00Z 2011-09-08T14:18:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/134 |
url |
http://hdl.handle.net/10400.18/134 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hum Reprod Update. 2010 Sep-Oct;16(5):525-42. Epub 2010 Mar 18 1355-4786 doi:10.1093/humupd/dmq005 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132080175579136 |