Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

围产期接触与人类相关的持久性有机污染物混合物:对 CD-1 小鼠乳腺发育、卵巢卵泡发生和肝脏的影响

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作者:Silje Modahl Johanson, Erik Ropstad, Gunn Charlotte Østby, Mona Aleksandersen, Galia Zamaratskaia, Gudrun Seeberg Boge, Ruth Halsne, Cathrine Trangerud, Jan Ludvig Lyche, Hanne Friis Berntsen, Karin Elisabeth Zimmer, Steven Verhaegen

Abstract

The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

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