Evaluation of changes in methylmercury accumulation in the developing rat brain and its effects: a study with consecutive and moderate dose exposure throughout gestation and lactation periods.
Methylmercury (MeHg) can be transferred to the fetus through the placenta and to newborn offspring through breast milk. The higher mercury (Hg) accumulation and susceptibility to toxicity in the fetus than in the mother during the gestation period is well known. However, the contribution of MeHg exposure through breast milk to the brain Hg concentration in offspring is not clear. The purposes of this study were to evaluate the changes in Hg concentration in the brain of offspring and its effects on the developing rat brain, based on consecutive and moderate doses of MeHg throughout gestation and lactation. Adult female rats were given a diet containing 5 ppm Hg (as MeHg) for 8 weeks. The administration level was thought not to cause adverse effects in adult rats. The rats were then mated and subsequently given the same diet throughout gestation and after parturition. The newborn offspring were placed with the mothers until postnatal day 30. The offspring were exposed to MeHg throughout their intrauterine life through the placenta, and during the postnatal developing phase via contaminated milk. Furthermore, they were given the same diet containing MeHg for 2 months following weaning. On the day of parturition, the concentration of Hg in the brains of newborns was 1.4 times higher than that in the mothers. During the suckling period the concentration in the brain of the offspring rapidly declined to 1/5 of that at birth, suggesting that MeHg transport by milk was limited while the brain and body volumes increased rapidly. The concentration increased gradually again after the offspring started the contaminated diet. In behavioral tests performed at 5 and 6 weeks of age, MeHg-exposed rats showed a significant deficit in motor coordination in the rotarod test and a learning disability in the passive avoidance response test, compared with controls. Histopathologically, focal cerebellar dysplasia, including the heterotopic location of Purkinje cells and granule cells, was observed. These abnormalities may be induced by the effect of highly accumulated MeHg in the brain during the gestation period. Thus, although offspring are subjected to consecutive and moderate dose MeHg exposure throughout both the gestation and suckling periods, the risk is especially high during gestation but may decrease during lactation.
Sakamoto
Mineshi
M
Department of Epidemiology, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan. sakamoto@nimd.go.jp
Kakita
Akiyoshi
A
Wakabayashi
Koichi
K
Takahashi
Hitoshi
H
Nakano
Atsuhiro
A
Akagi
Hirokatsu
H
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D007774:Lactation; D018811:Maternal Exposure; D018782:Maze Learning / Q000187:drug effects; D008628:Mercury / Q000378:metabolism* / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D008892:Milk; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D008767:Methylmercury Compounds; D008628:Mercury