4.7 Article

Alteration in Neonatal Nutrition Causes Perturbations in Hypothalamic Neural Circuits Controlling Reproductive Function

期刊

JOURNAL OF NEUROSCIENCE
卷 32, 期 33, 页码 11486-11494

出版社

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.6074-11.2012

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资金

  1. National Institutes of Health [DK84142]
  2. Fondation pour la Recherche Medicale
  3. Danone Institute
  4. EU [266408]
  5. Agence Nationale de la Recherche [ANR-08-JCJC-0055-01, ANR-09-BLAN-0267, ANR 11 BSV1 02102]
  6. French Ministere delegue a la Recherche et aux Nouvelles Technologies
  7. Agence Nationale de la Recherche (ANR) [ANR-08-JCJC-0055, ANR-09-BLAN-0267] Funding Source: Agence Nationale de la Recherche (ANR)

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It is increasingly accepted that alterations of the early life environment may have lasting impacts on physiological functions. In particular, epidemiological and animal studies have indicated that changes in growth and nutrition during childhood and adolescence can impair reproductive function. However, the precise biological mechanisms that underlie these programming effects of neonatal nutrition on reproduction are still poorly understood. Here, we used a mouse model of divergent litter size to investigate the effects of early postnatal overnutrition and undernutrition on the maturation of hypothalamic circuits involved in reproductive function. Neonatally undernourished females display attenuated postnatal growth associated with delayed puberty and defective development of axonal projections from the arcuate nucleus to the preoptic region. These alterations persist into adulthood and specifically affect the organization of neural projections containing kisspeptin, a key neuropeptide involved in pubertal activation and fertility. Neonatal overfeeding also perturbs the development of neural projections from the arcuate nucleus to the preoptic region, but it does not result in alterations in kisspeptin projections. These studies indicate that alterations in the early nutritional environment cause lasting and deleterious effects on the organization of neural circuits involved in the control of reproduction, and that these changes are associated with lifelong functional perturbations.

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