Transgenerational effects of maternal exposure to chemicals on the functional development of the brain in the offspring.
In order to prevent health risk from environmental chemicals, particularly for progeny, we have been performing a risk assessment for various chemicals including therapeutic agents. This paper reports the functional effects of maternal exposure to psychoactive drugs, anticancer drugs, or herbicides on the offspring of rats. Maternal exposure to imipramine in a dose equivalent to the therapeutic dose per unit body weight induced hyperthermic response to chlorpromazine in the male offspring, while normal control rats showed a marked hypothermia. Exposure to ethosuximide resulted in an increase in play fighting behavior in young offspring that was fostered by lactating normal mothers. Single exposures to nimustine or cisplatin, anticancer drugs, at a different gestational stage resulted in an acceleration of growth when exposed at the earlier stage of gestation. Moreover, cisplatin-exposed rats were emotionally unstable, showing a short latent time to the first line-crossing in an open-field during infantile period. The rats exposed to glufosinate ammonium, an herbicide, during the time of neurogenesis in the hippocampus showed a decrease in the wet-dog shakes response to kainic acid at six weeks of age. These results suggest that maternal exposure to chemicals during pregnancy induces a variety of functional abnormalities in the brain of the offspring dependent on the pharmacologic action of chemicals and the stage of gestation even with a single exposure.
Fujii
T
T
Teikyo University School of Medicine, Tokyo, Japan.
D000374:Aggression / Q000187:drug effects; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology; D002746:Chlorpromazine / Q000009:adverse effects; D002945:Cisplatin / Q000494:pharmacology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004644:Emotions / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005013:Ethosuximide / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005334:Fever / Q000139:chemically induced; D005865:Gestational Age; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D006540:Herbicides / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology; D007035:Hypothermia / Q000139:chemically induced; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D018811:Maternal Exposure; D015376:Nimustine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D018570:Risk Assessment
D000613:Aminobutyrates; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D000970:Antineoplastic Agents; D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D006540:Herbicides; D011619:Psychotropic Drugs; D015376:Nimustine; C003121:phosphinothricin; D005013:Ethosuximide; D005974:Glutamate-Ammonia Ligase; D007099:Imipramine; D002945:Cisplatin; D007608:Kainic Acid; D002746:Chlorpromazine