This proposal focuses on three forms of light perception by the mammalian fetus: maternal-fetal communication of circadian phase, direct perception of light in utero by the fetus, and maternal-fetal communication of daylength. Maternal-fetal communication of circadian phase will be studied in rats. Deoxyglucose and vasopressin mRNA autoradiography are used to monitor the circadian oscillations of a biological clock in the fetal suprachiasmatic nuclei (SCN), while pineal N-acetyltransferase activity and drinking behavior are used to monitor the developing circadian system during the postnatal period. Studies will focus on the mechanism of maternal-fetal coordination, with emphasis on the food ingestion rhythm as the maternal signal. The physiological significance of this prenatal communication will be examined by addressing the potential role of the fetal SCN in the circadian-gated initiation of birth and determining whether the developing circadian system functions normally in the absence of the prenatal maternal signal. The possibility of the direct perception of light in utero by the fetus will be studied in rodents with precocious offspring. The potential for direct light-induced activation of metabolic activity in the fetal SCN of guinea pigs will be examined; deoxyglucose autoradiography will be used to monitor the metabolic activity of the fetal nuclei. Postnatal behavior in spiny mice will be used as a means of examining prenatal influences (such as direct entrainment by light) on developing circadian phase. Maternal-fetal communication of daylength will be studied in Djungarian hamsters. Testicular weight will be used to study the influence of prenatal photoperiod on postnatal reproductive development. The role of maternal melatonin in the prenatal communication will be further defined. The involvement of maternal melatonin in phase communication in this photoperiod communication will also be examined. Finally, the physiological significance of phase communication for proper postnatal photoperiodic responses will be investigated. The results of these studies will advance our knowledge of the mechanisms and physiological significance of light perception by the mammalian fetus.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD014427-10
Application #
3312596
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1981-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Bae, Kiho; Weaver, David R (2003) Light-induced phase shifts in mice lacking mPER1 or mPER2. J Biol Rhythms 18:123-33
Gotter, Anthony L (2003) Tipin, a novel timeless-interacting protein, is developmentally co-expressed with timeless and disrupts its self-association. J Mol Biol 331:167-76
Shearman, L P; Weaver, D R (2001) Distinct pharmacological mechanisms leading to c-fos gene expression in the fetal suprachiasmatic nucleus. J Biol Rhythms 16:531-40
Bae, K; Jin, X; Maywood, E S et al. (2001) Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron 30:525-36
Shearman, L P; Zeitzer, J; Weaver, D R (1997) Widespread expression of functional D1-dopamine receptors in fetal rat brain. Brain Res Dev Brain Res 102:105-15
Weaver, D R (1997) Reproductive safety of melatonin: a ""wonder drug"" to wonder about. J Biol Rhythms 12:682-9
Weaver, D R; Roca, A L; Reppert, S M (1995) c-fos and jun-B mRNAs are transiently expressed in fetal rodent suprachiasmatic nucleus following dopaminergic stimulation. Brain Res Dev Brain Res 85:293-7
Weaver, D R; Reppert, S M (1995) Definition of the developmental transition from dopaminergic to photic regulation of c-fos gene expression in the rat suprachiasmatic nucleus. Brain Res Mol Brain Res 33:136-48
Viswanathan, N; Weaver, D R; Reppert, S M et al. (1994) Entrainment of the fetal hamster circadian pacemaker by prenatal injections of the dopamine agonist SKF 38393. J Neurosci 14:5393-8
Roca, A L; Weaver, D R; Reppert, S M (1993) Serotonin receptor gene expression in the rat suprachiasmatic nuclei. Brain Res 608:159-65

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