title: Impaired development of female mouse offspring maternally exposed to simazine.
abstract: Simazine is a suspected endocrine disruptor and the second most commonly detected pesticide in surface and groundwater worldwide. We evaluated the toxicity of simazine in female mouse offspring with in utero and lactational exposure to the agent. Pregnant mice were exposed to environmentally relevant doses (from 5 to 500μg/kg) of simazine via oral administration, and their female offspring were then analyzed. The female offspring showed shortened anogenital distance and decreased whole body, ovarian, and uterine weights. Their ovaries showed increased apoptotic granulosa cells. In addition, expression of critical genes involved in regulation of cellular apoptosis and proliferation was significantly downregulated in the ovaries of simazine-exposed mice. Moreover, in vitro exposure of human granulosa cell-derived KGN cells to simazine (0.003-1nM) resulted in decreased viability and proliferation. Thus, the present study demonstrates that maternal exposure to low doses of simazine impairs normal development of female offspring via disturbance of cellular apoptosis and proliferation.
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea; Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Seeun
authors.initials: S
authors.lastname: Park
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sarang
authors.initials: S
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: kangseok@cau.ac.kr.
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: jeehyeon@cau.ac.kr.
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D018811:Maternal Exposure; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012839:Simazine / Q000633:toxicity*
chemical_list: D006540:Herbicides; D012839:Simazine
keywords: Apoptosis; Maternal exposure; Ovary; Proliferation; Reproductive toxicology