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

Author(s):Show less -

Motta-Teixeira, Livia Clemente ^[1] ; Machado-Nils, Aline Vilar ^[2] ; Battagello, Daniella Sabino ^[3] ; Diniz, Giovanne Baroni ^[3] ; Andrade-Silva, Jessica ^[1] ; Silva Jr, Sinesio ; Matos, Raphael Afonso ^[4] ; do Amaral, Fernanda Gaspar ^{[5, 4]} ; Xavier, Gilberto Fernando ^[2] ; Bittencourt, Jackson Cioni ^[3] ; Reiter, Russel J. ^[6] ; Lucassen, Paul John ^[7] ; Korosi, Aniko ^[7] ; Cipolla-Neto, Jose ^[4]

Affiliation

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Av Lineu Prestes 1524, Bldg 1, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Biosci Inst, Dept Physiol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, SP - Brazil

^[4] Silva Jr, Jr., Sinesio, Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Av Lineu Prestes 1524, Bldg 1, BR-05508000 Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo, Dept Physiol, Sao Paulo, SP - Brazil

^[6] Univ Texas San Antonio, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 - USA

^[7] Univ Amsterdam, Swammerdam Inst Life Sci, Brain Plast Grp, Amsterdam - Netherlands

• Document type: Journal article
• Source: Hormones and Behavior; v. 105, p. 146-156, SEP 2018.
• Web of Science Citations: 8

Abstract

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. (AU)

• FAPESP's process: 12/04554-8 - IDENTIFICATION, MOLECULAR CHARACTERIZATION, MAPPING AND COLOCALIZATION OF THE RECEPTOR 1 MELANIN-CONCENTRATING HORMONE IN MAMMARY GLAND OF LACTATING AND NON-LACTATING RATS.
• Grantee: Daniella Sabino Battagello
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/02224-1 - The existence of neurogenesis during the lactation period
• Grantee: Jackson Cioni Bittencourt
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/02748-0 - Study of the anatomical basis for a volume transmission mechanism on the Melanin Concentrating Hormone [MCH] peptidergic system
• Grantee: Giovanne Baroni Diniz
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 10/52068-0 - The putative envolvement of melanin-concentrating hormone in the control of lactation
• Grantee: Jackson Cioni Bittencourt
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/22313-3 - Influence of the absence of maternal melatonin during pregnancy and lactation on neurogenesis and on somatic and sensorimotor development of the offspring.
• Grantee: Lívia Clemente Motta Teixeira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/50457-0 - Melatonin and the control of energy metabolism: basic, clinical and epidemiological research
• Grantee: José Cipolla Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/18941-4 - Effects of maternal melatonin deprivation during pregnancy and lactation on the offspring neuroimmune system
• Grantee: Lívia Clemente Motta Teixeira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate