GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation

Giuliana Pellegrino, Marion Martin, Cécile Allet, Tori Lhomme, Sarah Geller, Delphine Franssen, Virginie Mansuy, Maria Manfredi-Lozano, Adrian Coutteau-Robles, Virginia Delli, S. Rasika, Danièle Mazur, Anne Loyens, Manuel Tena-Sempere, Juergen Siepmann, François P. Pralong, Philippe Ciofi, Gabriel Corfas, Anne Simone Parent, Sergio R. OjedaAriane Sharif, Vincent Prevot

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1660-1672
Number of pages13
JournalNature neuroscience
Volume24
Issue number12
DOIs
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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