Effects of perinatal exposure to low-dose cadmium on thyroid hormone-related and sex hormone receptor gene expressions in brain of offspring.
Perinatal cadmium (Cd) exposure has been shown to alter behaviors and reduce learning ability of offspring. A few studies have shown that Cd reduced serum thyroid hormones (THs), which are important for brain development during the perinatal period. Brain specific genes, neurogranin (RC3) and myelin basic protein (BMP), are known to be regulated by TH through TH receptors (TR). It has been suggested that RC3 may play roles in memory and learning. In addition, Cd has been suggested to have estrogen-like activity. To evaluate the effects of perinatal low-dose exposure to Cd on thyroid hormone-related gene (RC3, TR-beta1, MBP, RAR-beta) and sex hormone receptor gene (ER-alpha, ER-beta and PgR) expressions in the brain and on behaviors of offspring, mice were administered with 10ppm Cd (from gestational day 1 to postnatal day 10) and/or 0.025% methimazole (MMI; anti-thyroid drug) (from gestational day 12 to postnatal day 10) in drinking water. Also, 0.1% MMI was administered as a positive control (high MMI group). RC3 mRNA expression was reduced in the female brain of combined exposure and high MMI groups and was negatively correlated with the activity in the open-field. ER-alpha, ER-beta and PgR mRNA expressions were decreased in male and female Cd, and female Cd+MMI groups, respectively; among these changes the reduced expression of PgR was opposite to estrogenic action. These results suggested that perinatal exposure to Cd disrupted the gene expressions of sex hormone receptors, which could not be considered to be a result of estrogenic action. Our study indicates that alteration in the gene expressions of RC3 and sex hormone receptors in the brain induced by perinatal Cd and MMI exposure might be one mechanism of developmental toxicity of Cd.
Ishitobi
Hiromi
H
Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan. hiromi_ishitobi@urmc.rochester.edu
Mori
Kohki
K
Yoshida
Katsumi
K
Watanabe
Chiho
C
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002104:Cadmium; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000528:radiation effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D012739:Gonadal Steroid Hormones; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein; D051579:Neurogranin / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D013963:Thyroid Hormones / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D002104:Cadmium; D014284:Triiodothyronine; D051579:Neurogranin