Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

被引:99
作者
Axelstad, Marta [1 ]
Boberg, Julie [1 ]
Hougaard, Karin Sorig [2 ]
Christiansen, Sofie [1 ]
Jacobsen, Pernille Rosenskjold [1 ]
Mandrup, Karen Riiber [1 ]
Nellemann, Christine [1 ]
Lund, Soren Peter [2 ]
Hass, Ulla [1 ]
机构
[1] Tech Univ Denmark, Natl Food Inst, Div Toxicol & Risk Assessment, DK-2860 Soborg, Denmark
[2] Natl Res Ctr Working Environm, DK-2100 Copenhagen O, Denmark
关键词
Thyroid hormone disrupting chemicals; OMC; Reproduction; Sperm counts; Developmental neurotoxicity; Rat; Behavior; IN-VIVO; GENERATION REPRODUCTION; ESTROGENIC ACTIVITY; THYROID-FUNCTION; HORMONE-LEVELS; ADULT-RATS; 5-DEIODINASE; INHIBITION; ESTRADIOL; TOXICITY;
D O I
10.1016/j.taap.2010.10.031
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T-4), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T-4) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T-4 deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:278 / 290
页数:13
相关论文
共 42 条
[1]
HYPERACTIVITY AND SPATIAL MAZE-LEARNING IMPAIRMENT OF ADULT-RATS WITH TEMPORARY NEONATAL-HYPOTHYROIDISM [J].
AKAIKE, M ;
KATO, N ;
OHNO, H ;
KOBAYASHI, T .
NEUROTOXICOLOGY AND TERATOLOGY, 1991, 13 (03) :317-322
[2]
A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration [J].
Ausó, E ;
Lavado-Autric, R ;
Cuevas, E ;
del Rey, FE ;
de Escobar, GM ;
Berbel, P .
ENDOCRINOLOGY, 2004, 145 (09) :4037-4047
[3]
Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes [J].
Axelstad, Marta ;
Hansen, Pernille Reimar ;
Boberg, Julie ;
Bonnichsen, Mia ;
Nellemann, Christine ;
Lund, Soren Peter ;
Hougaard, Karin Sorig ;
Hass, Ulla .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2008, 232 (01) :1-13
[4]
Biegel LB, 1998, TOXICOL SCI, V44, P116, DOI 10.1093/toxsci/44.2.116
[5]
EVIDENCE FOR DECREASING QUALITY OF SEMEN DURING PAST 50 YEARS [J].
CARLSEN, E ;
GIWERCMAN, A ;
KEIDING, N ;
SKAKKEBAEK, NE .
BRITISH MEDICAL JOURNAL, 1992, 305 (6854) :609-613
[6]
CAVALIERI RR, 1981, PHARMACOL REV, V33, P55
[7]
CHRISTIANSEN S, THESIS TU DENMARK, P218
[8]
PCBs, thyroid hormones, and ototoxicity in rats: Cross-fostering experiments demonstrate the impact of postnatal lactation exposure [J].
Crofton, KM ;
Kodavanti, PRS ;
Derr-Yellin, EC ;
Casey, AC ;
Kehn, LS .
TOXICOLOGICAL SCIENCES, 2000, 57 (01) :131-140
[9]
Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat [J].
Gilbert, Mary E. ;
Sui, Li .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2008, 116 (06) :752-760
[10]
Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency [J].
Gilbert, ME ;
Sui, L .
BRAIN RESEARCH, 2006, 1069 (01) :10-22