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

• Published in: Nature neuroscience Vol. 24; no. 12; pp. 1660 - 1672
• Main Authors: Pellegrino, Giuliana, Martin, Marion, Allet, Cécile, Lhomme, Tori, Geller, Sarah, Franssen, Delphine, Mansuy, Virginie, Manfredi-Lozano, Maria, Coutteau-Robles, Adrian, Delli, Virginia, Rasika, S., Mazur, Danièle, Loyens, Anne, Tena-Sempere, Manuel, Siepmann, Juergen, Pralong, François P., Ciofi, Philippe, Corfas, Gabriel, Parent, Anne-Simone, Ojeda, Sergio R., Sharif, Ariane, Prevot, Vincent
• Format: Journal Article Web Resource
• Language: English
• Published: New York Nature Publishing Group US 01.12.2021; Nature Publishing Group
• Subjects: 14/32; 42/35; 45/77; 631/378/2582; 631/443/319/367/1562; 82/1; 82/51; 9/74; 96/63; Animal Genetics and Genomics; Astrocytes; Astrocytes - metabolism; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Bisphenol A; Brain; Brain research; Cellular signal transduction; Cognitive science; Development; Dopamine D2 receptors; Endocrinologie, métabolisme & nutrition; Endocrinology, metabolism & nutrition; Fertility; Gliogenesis; Gonadotropin releasing hormone; Gonadotropin-Releasing Hormone - metabolism; Gonadotropins; Human health sciences; Hypothalamus; Hypothalamus - physiology; Infants; Integration; Maturation; Neural circuitry; Neural networks; Neurobiology; Neurons; Neurons - physiology; Neurosciences; Pediatrics; Physiological aspects; Pituitary; Pituitary (anterior); Prostaglandin D2; Pédiatrie; Rodents; Sciences de la santé humaine; Sexual Maturation - physiology; Signaling; Wiring; France
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-021-00960-z

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 D 2 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. GnRH neurons control their own connectivity and function as well as the sexual maturation of the individual by using prostaglandin D 2 DP1 signaling to recruit and stably associate with newborn astrocytes in the preoptic region during infancy in rodents.