The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice

Yan Huang; Nina Bucevic; Carmen Coves; Natalia Felipe-Medina; Marina Marcet-Ortega; Nikoleta Nikou; Cristina Madrid-Sandín; Maria López-Panadés; Carolina Buza Tarna; Neus Ferrer Miralles; Antoni Iborra Obiols; Anna Pujol; Alberto M Pendas; Ignasi Roig

doi:10.7554/elife.96052

The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice

Yan Huang, Nina Bucevic, Carmen Coves, Natalia Felipe-Medina, Marina Marcet-Ortega, Nikoleta Nikou, Cristina Madrid-Sandín, Maria López-Panadés, Carolina Buza Tarna, Neus Ferrer Miralles, Antoni Iborra Obiols, Anna Pujol, Alberto M Pendas, Ignasi Roig

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

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Resum

La infertilitat afecta fins a un 12% de les parelles del món, i hi ha factors genètics que contribueixen en gairebé la meitat dels casos. Els avenços en tecnologies genòmiques han portat al descobriment de gens com Bend2, que tenen un paper crucial en la gametogènesi. Al testicle, el gen Bend2 expressa dues isoformes proteiques: una de mida completa i una altra més petita. L'ablació d'ambdues proteïnes provoca l'aturada de la producció d'espermatozous. Com que el locus del gen Bend2 es troba al cromosoma X, i els mutants Bend2-/y són estèrils, el paper del gen Bend2 en la producció d'òvuls ha resultat difícil d'entendre. En aquest estudi hem emprat una nova mutació del gen Bend2 que bloqueja l'expressió de la proteïna completa però permet l'expressió de la isoforma més petita. De manera interessant, aquesta mutació no provoca esterilitat masculina i afecta lleument la producció d'espermatozous. Això ens ha permès estudiar el paper del gen Bend2 en la producció d'òvuls. Les nostres troballes demostren que el gen Bend2 complet és prescindible per a la fertilitat masculina, i l'ablació provoca un establiment més baix de la reserva ovàrica. Aquests resultats revelen un paper crucial del gen Bend2 en la producció d'òvuls i ofereixen informació sobre els mecanismes subjacents al manteniment de la reserva ovàrica. A més, aquestes troballes tenen importància per a la diagnosi de la infertilitat humana.

Idioma original	Anglès
Número d’article	RP96052
Nombre de pàgines	24
Revista	eLife
Volum	13
DOIs	https://doi.org/10.7554/elife.96052
Estat de la publicació	Publicada - 20 d’ag. 2025

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10.7554/elife.96052Llicència: Creative Commons Reconeixement

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https://www.mendeley.com/catalogue/eb563c2e-ad4b-3bb3-acd3-435b814166e0/

FUNCTIONAL ANALYSIS OF MAMMALIAN GAMETOGENESIS
Roig Navarro, I. (Investigador/a principal), López Panadés, M. (Col.laborador/a), Madrid Sandín, C. (Col.laborador/a), Maldonado Linares, A. (Col.laborador/a), Nikou ., N. (Col.laborador/a) & Gubern Burset, A. (Investigador/a)
Fons Social Europeu
1/09/23 → 31/08/26
Projecte: Projectes i Ajuts a la Recerca
Study of the impact of COVID-19 on male fertility. Elucidating the mechanisms of testicular disfunction and testing treatments to overcome it
Roig Navarro, I. (Investigador/a principal) & López Panadés, M. (Col.laborador/a)
Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)
20/10/22 → 19/10/24
Projecte: Projectes i Ajuts a la Recerca
FUNCTIONAL STUDY OF MAMMALIAN SPERMATOGENESIS AND OOGENESIS.
Roig Navarro, I. (Investigador/a principal), Huang, Y. (Col.laborador/a), Maldonado Linares, A. (Col.laborador/a), Nikou ., N. (Col.laborador/a) & Madrid Sandín, C. (Col.laborador/a)
1/01/20 → 30/09/23
Projecte: Projectes i Ajuts a la Recerca

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Huang, Y., Bucevic, N., Coves, C., Felipe-Medina, N., Marcet-Ortega, M., Nikou, N., Madrid-Sandín, C., López-Panadés, M., Buza Tarna, C., Miralles, N. F., Iborra Obiols, A., Pujol, A., Pendas, A. M., & Roig, I. (2025). The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice. eLife, 13, Article RP96052. https://doi.org/10.7554/elife.96052

@article{de6df149b9774effafee84581f287c9a,

title = "The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice",

abstract = "Infertility affects up to 12\% of couples globally, with genetic factors contributing to nearly half of the cases. Advances in genomic technologies have led to the discovery of genes like Bend2, which play a crucial role in gametogenesis. In the testis, Bend2 expresses two protein isoforms: full-length and a smaller one. Ablation of both proteins results in an arrested spermatogenesis. Because the Bend2 locus is on the X chromosome, and the Bend2-/y mutants are sterile, BEND2{\textquoteright}s role in oogenesis remained elusive. In this study, we employed a novel Bend2 mutation that blocks the expression of the full-length BEND2 protein but allows the expression of the smaller BEND2 isoform. Interestingly, this mutation does not confer male sterility and mildly affects spermatogenesis. Thus, it allowed us to study the role of BEND2 in oogenesis. Our findings demonstrate that full-length BEND2 is dispensable for male fertility, and its ablation leads to a reduced establishment of the ovarian reserve. These results reveal a critical role for full-length BEND2 in oogenesis and provide insights into the mechanisms underlying the establishment of the ovarian reserve. Furthermore, these findings hold relevance for the diagnostic landscape of human infertility.",

keywords = "Bend2, Gametogenesis, Infertility, Meiosis, Ovarian reserve",

author = "Yan Huang and Nina Bucevic and Carmen Coves and Natalia Felipe-Medina and Marina Marcet-Ortega and Nikoleta Nikou and Cristina Madrid-Sand{\'i}n and Maria L{\'o}pez-Panad{\'e}s and \{Buza Tarna\}, Carolina and Miralles, \{Neus Ferrer\} and \{Iborra Obiols\}, Antoni and Anna Pujol and Pendas, \{Alberto M\} and Ignasi Roig",

year = "2025",

month = aug,

day = "20",

doi = "10.7554/elife.96052",

language = "English",

volume = "13",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

}

Huang, Y, Bucevic, N, Coves, C, Felipe-Medina, N, Marcet-Ortega, M, Nikou, N , Madrid-Sandín, C , López-Panadés, M, Buza Tarna, C, Miralles, NF, Iborra Obiols, A, Pujol, A, Pendas, AM & Roig, I 2025, 'The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice', eLife, vol. 13, RP96052. https://doi.org/10.7554/elife.96052

TY - JOUR

T1 - The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice

AU - Huang, Yan

AU - Bucevic, Nina

AU - Coves, Carmen

AU - Felipe-Medina, Natalia

AU - Marcet-Ortega, Marina

AU - Nikou, Nikoleta

AU - Madrid-Sandín, Cristina

AU - López-Panadés, Maria

AU - Buza Tarna, Carolina

AU - Miralles, Neus Ferrer

AU - Iborra Obiols, Antoni

AU - Pujol, Anna

AU - Pendas, Alberto M

AU - Roig, Ignasi

PY - 2025/8/20

Y1 - 2025/8/20

N2 - Infertility affects up to 12% of couples globally, with genetic factors contributing to nearly half of the cases. Advances in genomic technologies have led to the discovery of genes like Bend2, which play a crucial role in gametogenesis. In the testis, Bend2 expresses two protein isoforms: full-length and a smaller one. Ablation of both proteins results in an arrested spermatogenesis. Because the Bend2 locus is on the X chromosome, and the Bend2-/y mutants are sterile, BEND2’s role in oogenesis remained elusive. In this study, we employed a novel Bend2 mutation that blocks the expression of the full-length BEND2 protein but allows the expression of the smaller BEND2 isoform. Interestingly, this mutation does not confer male sterility and mildly affects spermatogenesis. Thus, it allowed us to study the role of BEND2 in oogenesis. Our findings demonstrate that full-length BEND2 is dispensable for male fertility, and its ablation leads to a reduced establishment of the ovarian reserve. These results reveal a critical role for full-length BEND2 in oogenesis and provide insights into the mechanisms underlying the establishment of the ovarian reserve. Furthermore, these findings hold relevance for the diagnostic landscape of human infertility.

AB - Infertility affects up to 12% of couples globally, with genetic factors contributing to nearly half of the cases. Advances in genomic technologies have led to the discovery of genes like Bend2, which play a crucial role in gametogenesis. In the testis, Bend2 expresses two protein isoforms: full-length and a smaller one. Ablation of both proteins results in an arrested spermatogenesis. Because the Bend2 locus is on the X chromosome, and the Bend2-/y mutants are sterile, BEND2’s role in oogenesis remained elusive. In this study, we employed a novel Bend2 mutation that blocks the expression of the full-length BEND2 protein but allows the expression of the smaller BEND2 isoform. Interestingly, this mutation does not confer male sterility and mildly affects spermatogenesis. Thus, it allowed us to study the role of BEND2 in oogenesis. Our findings demonstrate that full-length BEND2 is dispensable for male fertility, and its ablation leads to a reduced establishment of the ovarian reserve. These results reveal a critical role for full-length BEND2 in oogenesis and provide insights into the mechanisms underlying the establishment of the ovarian reserve. Furthermore, these findings hold relevance for the diagnostic landscape of human infertility.

KW - Bend2

KW - Gametogenesis

KW - Infertility

KW - Meiosis

KW - Ovarian reserve

UR - https://www.mendeley.com/catalogue/eb563c2e-ad4b-3bb3-acd3-435b814166e0/

U2 - 10.7554/elife.96052

DO - 10.7554/elife.96052

M3 - Article

SN - 2050-084X

VL - 13

JO - eLife

JF - eLife

M1 - RP96052

ER -

The full length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice

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FUNCTIONAL ANALYSIS OF MAMMALIAN GAMETOGENESIS

Study of the impact of COVID-19 on male fertility. Elucidating the mechanisms of testicular disfunction and testing treatments to overcome it

FUNCTIONAL STUDY OF MAMMALIAN SPERMATOGENESIS AND OOGENESIS.

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