TY - JOUR
T1 - GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation
AU - Pellegrino, Giuliana
AU - Martin, Marion
AU - Allet, Cécile
AU - Lhomme, Tori
AU - Geller, Sarah
AU - Franssen, Delphine
AU - Mansuy, Virginie
AU - Manfredi-Lozano, Maria
AU - Coutteau-Robles, Adrian
AU - Delli, Virginia
AU - Rasika, S.
AU - Mazur, Danièle
AU - Loyens, Anne
AU - Tena-Sempere, Manuel
AU - Siepmann, Juergen
AU - Pralong, François P.
AU - Ciofi, Philippe
AU - Corfas, Gabriel
AU - Parent, Anne Simone
AU - Ojeda, Sergio R.
AU - Sharif, Ariane
AU - Prevot, Vincent
N1 - Funding Information:
G.P. and M.M. were PhD students funded by the University of Lille and C.A. by the CHU Lille. We are most grateful to S. Charpier (Institut du Cerveau, UPMC-P6 UM 75, Paris, France) for precious insights in analyzing electrophysiological data and P. Giacobini (Inserm, Lille, France) for comments on the manuscript. We thank A. Dawid for data analysis (LiPhy, Grenoble), A. Caillet (U1172), N. Jouy (cytometry core facility, UMS2014-US41), M. Tardivel and A. Bongiovanni (microscopy core facility, UMS2014-US41), M. Fourdrinier (animal core facility, University of Lille) and A. Gérard (University of Liège) for expert technical assistance. We are indebted to G. Ternier for help in imaging analysis using IMARIS and to S. Nampoothiri for her work on the manuscript. This research was supported by the Fondation pour la Recherche Médicale (FRM, INE 2002), Agence Nationale de la Recherche (ANR, France) ANR-15-CE14–0025 (to V.P.), ANR-16-CE37-0006 (to V.P.), ANR-17-CE16-0015 (to V.P. and P.C.), the laboratory of excellence DISTALZ (ANR-11-LABX-0009 to V.P.) and I-SITE ULNE (ANR-16-IDEX-0004 ULNE to V.P.), the Association pour l’Etude des Anomalies Congénitales (AEAC; to A.S.) and the National Institutes of Health (1RO1 HD-084542 and 8P51OD011092 to S.R.O.).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/12
Y1 - 2021/12
N2 - Neurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D2 receptor DP1 signaling mechanism during infancy to recruit newborn astrocytes that ‘escort’ them into adulthood, and that the impairment of postnatal hypothalamic gliogenesis markedly alters sexual maturation by preventing this recruitment, a process mimicked by the endocrine disruptor bisphenol A. Inhibition of DP1 signaling in the infantile preoptic region, where GnRH cell bodies reside, disrupts the correct wiring and firing of GnRH neurons, alters minipuberty or the first activation of the hypothalamic–pituitary–gonadal axis during infancy, and delays the timely acquisition of reproductive capacity. These findings uncover a previously unknown neuron-to-neural-progenitor communication pathway and demonstrate that postnatal astrogenesis is a basic component of a complex set of mechanisms used by the neuroendocrine brain to control sexual maturation.
AB - Neurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D2 receptor DP1 signaling mechanism during infancy to recruit newborn astrocytes that ‘escort’ them into adulthood, and that the impairment of postnatal hypothalamic gliogenesis markedly alters sexual maturation by preventing this recruitment, a process mimicked by the endocrine disruptor bisphenol A. Inhibition of DP1 signaling in the infantile preoptic region, where GnRH cell bodies reside, disrupts the correct wiring and firing of GnRH neurons, alters minipuberty or the first activation of the hypothalamic–pituitary–gonadal axis during infancy, and delays the timely acquisition of reproductive capacity. These findings uncover a previously unknown neuron-to-neural-progenitor communication pathway and demonstrate that postnatal astrogenesis is a basic component of a complex set of mechanisms used by the neuroendocrine brain to control sexual maturation.
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UR - http://www.scopus.com/inward/citedby.url?scp=85119422810&partnerID=8YFLogxK
U2 - 10.1038/s41593-021-00960-z
DO - 10.1038/s41593-021-00960-z
M3 - Article
C2 - 34795451
AN - SCOPUS:85119422810
SN - 1097-6256
VL - 24
SP - 1660
EP - 1672
JO - Nature neuroscience
JF - Nature neuroscience
IS - 12
ER -