BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
CONTEXT: Primary ovarian insufficiency (POI) is a frequently occurring disorder affecting approximately 1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone, leads to infertility. Alt...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2020
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/23371
- Acceso en línea:
- https://doi.org/10.1210/clinem/dgz226
https://repository.urosario.edu.co/handle/10336/23371
- Palabra clave:
- Bone morphogenic protein receptor
Follicular development
Infertility
- Rights
- License
- Abierto (Texto Completo)
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oai:repository.urosario.edu.co:10336/23371 |
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Repositorio EdocUR - U. Rosario |
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ebb21d05-6795-4b53-b3a8-3c1b76876f4f-177273e86-df40-4d8e-90a6-4e1c78ea40d6-15643f674-ea81-4f8c-9269-b42ae0baf9d7-14c21c987-eb06-4b96-ad35-8c9d99daef4a-17edfad1e-b100-49f3-8835-08c0ad0ab30e-179782770-10e716caf-e5ec-49bd-9955-66d1f21ea8f6-18d0624f6-6054-4c8f-a5ed-9d5a431503a2-12020-05-26T00:01:28Z2020-05-26T00:01:28Z2020CONTEXT: Primary ovarian insufficiency (POI) is a frequently occurring disorder affecting approximately 1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone, leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene mutations, most cases remain idiopathic. OBJECTIVE: To identify and to functionally validate new sequence variants in 2 genes that play a key role in mammalian ovarian function, BMPR1A and BMPR1B (encoding for bone morphogenic protein receptor), leading to POI. METHODS: The impact on bone morphogenic protein (BMP) signaling of BMPR1A and BMPR1B variants, previously identified by whole-exome sequencing on 69 women affected by isolated POI, was established by different in vitro functional experiments. RESULTS: We demonstrate that the BMPR1A-p.Arg442His and BMPR1B-p.Phe272Leu variants are correctly expressed and located but lead to an impairment of downstream BMP signaling. CONCLUSION: In accordance with infertility observed in mice lacking Bmpr1a in the ovaries and in Bmpr1b-/- mice, our results unveil, for the first time, a link between BMPR1A and BMPR1B variants and the origin of POI. We show that BMP signaling impairment through specific BMPR1A and BMPR1B variants is a novel pathophysiological mechanism involved in human POI. We consider that BMPR1A and BMPR1B variants constitute genetic biomarkers of the origin of POI and have clinical utility. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.application/pdfhttps://doi.org/10.1210/clinem/dgz226https://repository.urosario.edu.co/handle/10336/23371engNLM (Medline)No. 4The Journal of clinical endocrinology and metabolismVol. 105The Journal of clinical endocrinology and metabolism, Vol.105, No.4 (2020)https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081945965&doi=10.1210%2fclinem%2fdgz226&partnerID=40&md5=5db06b813c1defcea2896860b266c1adAbierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURBone morphogenic protein receptorFollicular developmentInfertilityBMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian InsufficiencyarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Renault, LuciePatiño, Liliana CMagnin, FrançoiseDelemer, BrigitteYoung, JacquesLaissue, PaulBinart, NadineBeau, Isabelle10336/23371oai:repository.urosario.edu.co:10336/233712022-05-02 07:37:20.939897https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co |
dc.title.spa.fl_str_mv |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
title |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
spellingShingle |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency Bone morphogenic protein receptor Follicular development Infertility |
title_short |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
title_full |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
title_fullStr |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
title_full_unstemmed |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
title_sort |
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency |
dc.subject.keyword.spa.fl_str_mv |
Bone morphogenic protein receptor Follicular development Infertility |
topic |
Bone morphogenic protein receptor Follicular development Infertility |
description |
CONTEXT: Primary ovarian insufficiency (POI) is a frequently occurring disorder affecting approximately 1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone, leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene mutations, most cases remain idiopathic. OBJECTIVE: To identify and to functionally validate new sequence variants in 2 genes that play a key role in mammalian ovarian function, BMPR1A and BMPR1B (encoding for bone morphogenic protein receptor), leading to POI. METHODS: The impact on bone morphogenic protein (BMP) signaling of BMPR1A and BMPR1B variants, previously identified by whole-exome sequencing on 69 women affected by isolated POI, was established by different in vitro functional experiments. RESULTS: We demonstrate that the BMPR1A-p.Arg442His and BMPR1B-p.Phe272Leu variants are correctly expressed and located but lead to an impairment of downstream BMP signaling. CONCLUSION: In accordance with infertility observed in mice lacking Bmpr1a in the ovaries and in Bmpr1b-/- mice, our results unveil, for the first time, a link between BMPR1A and BMPR1B variants and the origin of POI. We show that BMP signaling impairment through specific BMPR1A and BMPR1B variants is a novel pathophysiological mechanism involved in human POI. We consider that BMPR1A and BMPR1B variants constitute genetic biomarkers of the origin of POI and have clinical utility. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
publishDate |
2020 |
dc.date.accessioned.none.fl_str_mv |
2020-05-26T00:01:28Z |
dc.date.available.none.fl_str_mv |
2020-05-26T00:01:28Z |
dc.date.created.spa.fl_str_mv |
2020 |
dc.type.eng.fl_str_mv |
article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.spa.spa.fl_str_mv |
Artículo |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1210/clinem/dgz226 |
dc.identifier.uri.none.fl_str_mv |
https://repository.urosario.edu.co/handle/10336/23371 |
url |
https://doi.org/10.1210/clinem/dgz226 https://repository.urosario.edu.co/handle/10336/23371 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.citationIssue.none.fl_str_mv |
No. 4 |
dc.relation.citationTitle.none.fl_str_mv |
The Journal of clinical endocrinology and metabolism |
dc.relation.citationVolume.none.fl_str_mv |
Vol. 105 |
dc.relation.ispartof.spa.fl_str_mv |
The Journal of clinical endocrinology and metabolism, Vol.105, No.4 (2020) |
dc.relation.uri.spa.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081945965&doi=10.1210%2fclinem%2fdgz226&partnerID=40&md5=5db06b813c1defcea2896860b266c1ad |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
NLM (Medline) |
institution |
Universidad del Rosario |
dc.source.instname.spa.fl_str_mv |
instname:Universidad del Rosario |
dc.source.reponame.spa.fl_str_mv |
reponame:Repositorio Institucional EdocUR |
repository.name.fl_str_mv |
Repositorio institucional EdocUR |
repository.mail.fl_str_mv |
edocur@urosario.edu.co |
_version_ |
1814167725940932608 |