IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32347-4.html
   My bibliography  Save this article

Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice

Author

Listed:
  • Juan Roa

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Miguel Ruiz-Cruz

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Francisco Ruiz-Pino

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Rocio Onieva

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Maria J. Vazquez

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Maria J. Sanchez-Tapia

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Jose M. Ruiz-Rodriguez

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Veronica Sobrino

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Alexia Barroso

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Violeta Heras

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Inmaculada Velasco

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Cecilia Perdices-Lopez

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Claes Ohlsson

    (Sahlgrenska Academy, University of Gothenburg)

  • Maria Soledad Avendaño

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Vincent Prevot

    (Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition)

  • Matti Poutanen

    (Sahlgrenska Academy, University of Gothenburg
    University of Turku)

  • Leonor Pinilla

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Francisco Gaytan

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

  • Manuel Tena-Sempere

    (Instituto Maimónides de Investigación Biomédica de Córdoba
    University of Córdoba
    Hospital Universitario Reina Sofia
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III)

Abstract

Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.

Suggested Citation

  • Juan Roa & Miguel Ruiz-Cruz & Francisco Ruiz-Pino & Rocio Onieva & Maria J. Vazquez & Maria J. Sanchez-Tapia & Jose M. Ruiz-Rodriguez & Veronica Sobrino & Alexia Barroso & Violeta Heras & Inmaculada V, 2022. "Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32347-4
    DOI: 10.1038/s41467-022-32347-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32347-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32347-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Carlos A. Toro & Hollis Wright & Carlos F. Aylwin & Sergio R. Ojeda & Alejandro Lomniczi, 2018. "Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Brenda J. Reinhart & Frank J. Slack & Michael Basson & Amy E. Pasquinelli & Jill C. Bettinger & Ann E. Rougvie & H. Robert Horvitz & Gary Ruvkun, 2000. "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans," Nature, Nature, vol. 403(6772), pages 901-906, February.
    3. M. J. Vazquez & C. A. Toro & J. M. Castellano & F. Ruiz-Pino & J. Roa & D. Beiroa & V. Heras & I. Velasco & C. Dieguez & L. Pinilla & F. Gaytan & R. Nogueiras & M. A. Bosch & O. K. Rønnekleiv & A. Lom, 2018. "SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Akiko Doi & Gianmarco D. Suarez & Rita Droste & H. Robert Horvitz, 2023. "A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Chikako Ragan & Michael Zuker & Mark A Ragan, 2011. "Quantitative Prediction of miRNA-mRNA Interaction Based on Equilibrium Concentrations," PLOS Computational Biology, Public Library of Science, vol. 7(2), pages 1-11, February.
    3. Evangelia Lekka & Aleksandra Kokanovic & Simone Mosole & Gianluca Civenni & Sandro Schmidli & Artur Laski & Alice Ghidini & Pavithra Iyer & Christian Berk & Alok Behera & Carlo V. Catapano & Jonathan , 2022. "Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Yonghua Wang & Yan Li & Zhi Ma & Wei Yang & Chunzhi Ai, 2010. "Mechanism of MicroRNA-Target Interaction: Molecular Dynamics Simulations and Thermodynamics Analysis," PLOS Computational Biology, Public Library of Science, vol. 6(7), pages 1-19, July.
    5. Parawee Lekprasert & Michael Mayhew & Uwe Ohler, 2011. "Assessing the Utility of Thermodynamic Features for microRNA Target Prediction under Relaxed Seed and No Conservation Requirements," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-13, June.
    6. Zhen Shen & You-Hua Zhang & Kyungsook Han & Asoke K. Nandi & Barry Honig & De-Shuang Huang, 2017. "miRNA-Disease Association Prediction with Collaborative Matrix Factorization," Complexity, Hindawi, vol. 2017, pages 1-9, September.
    7. Seungwon Jung & Seung Hwan Ko & Narae Ahn & Jinsam Lee & Chang-Hwan Park & Jungwook Hwang, 2024. "Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32347-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.