The absence of maternal pineal melatonin rhythm during pregnancy and lactation impairs offspring physical growth, neurodevelopment, and behavior

Lívia Clemente Motta-Teixeira, Aline Vilar Machado-Nils, Daniella Sabino Battagello, Giovanne Baroni Diniz, Jéssica Andrade-Silva, Sinésio Silva, Raphael Afonso Matos, Fernanda Gaspar do Amaral, Gilberto Fernando Xavier, Jackson Cioni Bittencourt, Russel J. Reiter, Paul John Lucassen, Aniko Korosi, José Cipolla-Neto

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Maternal melatonin provides photoperiodic information to the fetus and thus influences the regulation and timing of the offspring's internal rhythms and preparation for extra-uterine development. There is clinical evidence that melatonin deprivation of both mother and fetus during pregnancy, and of the neonate during lactation, results in negative long-term health outcomes. As a consequence, we hypothesized that the absence of maternal pineal melatonin might determine abnormal brain programming in the offspring, which would lead to long-lasting implications for behavior and brain function. To test our hypothesis, we investigated in rats the effects of maternal melatonin deprivation during gestation and lactation (MMD) to the offspring and the effects of its therapeutic replacement. The parameters evaluated were: (1) somatic, physical growth and neurobehavioral development of pups of both sexes; (2) hippocampal-dependent spatial learning and memory of the male offspring; (3) adult hippocampal neurogenesis of the male offspring. Our findings show that MMD significantly delayed male offspring's onset of fur development, pinna detachment, eyes opening, eruption of superior incisor teeth, testis descent and the time of maturation of palmar grasp, righting reflex, free-fall righting and walking. Conversely, female offspring neurodevelopment was not affected. Later on, male offspring show that MMD was able to disrupt both spatial reference and working memory in the Morris Water Maze paradigm and these deficits correlate with changes in the number of proliferative cells in the hippocampus. Importantly, all the observed impairments were reversed by maternal melatonin replacement therapy. In summary, we demonstrate that MMD delays the appearance of physical features, neurodevelopment and cognition in the male offspring, and points to putative public health implications for night shift working mothers.

Original languageEnglish (US)
Pages (from-to)146-156
Number of pages11
JournalHormones and Behavior
StatePublished - Sep 2018
Externally publishedYes


  • Adult neurogenesis
  • Development
  • Melatonin
  • Neuroprotection
  • Reference memory
  • Spatial memory
  • Working memory

ASJC Scopus subject areas

  • Endocrinology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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