TY - JOUR
T1 - The absence of maternal pineal melatonin rhythm during pregnancy and lactation impairs offspring physical growth, neurodevelopment, and behavior
AU - Motta-Teixeira, Lívia Clemente
AU - Machado-Nils, Aline Vilar
AU - Battagello, Daniella Sabino
AU - Diniz, Giovanne Baroni
AU - Andrade-Silva, Jéssica
AU - Silva, Sinésio
AU - Matos, Raphael Afonso
AU - do Amaral, Fernanda Gaspar
AU - Xavier, Gilberto Fernando
AU - Bittencourt, Jackson Cioni
AU - Reiter, Russel J.
AU - Lucassen, Paul John
AU - Korosi, Aniko
AU - Cipolla-Neto, José
N1 - Funding Information:
We thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for funding the project. Are recipients of FAPESP grants: J.C.-N. ( 2014/50457-0 ); L.C.M.T. ( 2014/22313-3/2016/18941-4 ); D.S.B. ( 2012/04554-8 ); G.B.D. ( 2016/02748-0 ); J.C.B. ( 2010/52068-0 and 2016/02224-1 ); AK is supported by NWO (Meervoud grant). J.C.-N, J.C.B. and G.F.X. are Investigators with the Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq, National Council for Scientific and Technological Development].
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - Adult neurogenesis
KW - Development
KW - Melatonin
KW - Neuroprotection
KW - Reference memory
KW - Spatial memory
KW - Working memory
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U2 - 10.1016/j.yhbeh.2018.08.006
DO - 10.1016/j.yhbeh.2018.08.006
M3 - Article
C2 - 30114430
AN - SCOPUS:85052731548
VL - 105
SP - 146
EP - 156
JO - Hormones and Behavior
JF - Hormones and Behavior
SN - 0018-506X
ER -