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dc.contributor.authorCamera, Mattia
dc.contributor.authorRusso, Isabella
dc.contributor.authorZamboni, Valentina
dc.contributor.authorAmmoni, Alessandra
dc.contributor.authorRando, Simona
dc.contributor.authorMorellato, Alessandro
dc.contributor.authorCimino, Irene
dc.contributor.authorAngelini, Costanza
dc.contributor.authorGiacobini, Paolo
dc.contributor.authorOleari, Roberto
dc.contributor.authorAmoruso, Federica
dc.contributor.authorCariboni, Anna
dc.contributor.authorFranceschini, Isabelle
dc.contributor.authorTurco, Emilia
dc.contributor.authorDefilippi, Paola
dc.contributor.authorMerlo, Giorgio R
dc.date.accessioned2022-02-28T09:00:30Z
dc.date.available2022-02-28T09:00:30Z
dc.date.issued2022
dc.date.submitted2021-07-20
dc.identifier.issn1662-4548
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334489
dc.description.abstractp140Cap, encoded by the gene SRCIN1 (SRC kinase signaling inhibitor 1), is an adaptor/scaffold protein highly expressed in the mouse brain, participating in several pre- and post-synaptic mechanisms. p140Cap knock-out (KO) female mice show severe hypofertility, delayed puberty onset, altered estrus cycle, reduced ovulation, and defective production of luteinizing hormone and estradiol during proestrus. We investigated the role of p140Cap in the development and maturation of the hypothalamic gonadotropic system. During embryonic development, migration of Gonadotropin-Releasing Hormone (GnRH) neurons from the nasal placode to the forebrain in p140Cap KO mice appeared normal, and young p140Cap KO animals showed a normal number of GnRH-immunoreactive (-ir) neurons. In contrast, adult p140Cap KO mice showed a significant loss of GnRH-ir neurons and a decreased density of GnRH-ir projections in the median eminence, accompanied by reduced levels of GnRH and LH mRNAs in the hypothalamus and pituitary gland, respectively. We examined the number of kisspeptin (KP) neurons in the rostral periventricular region of the third ventricle, the number of KP-ir fibers in the arcuate nucleus, and the number of KP-ir punctae on GnRH neurons but we found no significant changes. Consistently, the responsiveness to exogenous KP in vivo was unchanged, excluding a cell-autonomous defect on the GnRH neurons at the level of KP receptor or its signal transduction. Since glutamatergic signaling in the hypothalamus is critical for both puberty onset and modulation of GnRH secretion, we examined the density of glutamatergic synapses in p140Cap KO mice and observed a significant reduction in the density of VGLUT-ir punctae both in the preoptic area and on GnRH neurons. Our data suggest that the glutamatergic circuitry in the hypothalamus is altered in the absence of p140Cap and is required for female fertility.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectNeuroscience
dc.subjectp140Cap
dc.subjectGnRH (Gonadotropin-Releasing Hormone)
dc.subjectkisspeptin
dc.subjectglutamate
dc.subjectfertility
dc.titlep140Cap Controls Female Fertility in Mice Acting via Glutamatergic Afference on Hypothalamic Gonadotropin-Releasing Hormone Neurons.
dc.typeArticle
dc.date.updated2022-02-28T09:00:29Z
prism.publicationNameFront Neurosci
prism.volume16
dc.identifier.doi10.17863/CAM.81907
dcterms.dateAccepted2022-01-20
rioxxterms.versionofrecord10.3389/fnins.2022.744693
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCimino, Irene [0000-0003-1397-5408]
dc.identifier.eissn1662-453X
cam.issuedOnline2022-02-14


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