title: Reproductive effects in F1 adult females exposed in utero to moderate to high doses of mono-2-ethylhexylphthalate (MEHP).
abstract: Phthalates are widely used as plasticizers in everyday products. Yet, studies on the effects of phthalates on female reproductive health are limited. In this study, pregnant C57/Bl6 mice were exposed via oral gavage to corn oil, 100, 500, or 1000mg/kg MEHP from gestational days 17-19. Reproductive lifespan was decreased by one month in the highest F1 exposure group (9.8±0.4 versus 11.1±0.6 months in control F1 females). F1 females exhibited delayed estrous onset at the two higher exposures and prolonged estrus was observed in all MEHP-exposed females. Serum FSH and estradiol were significantly elevated at the highest exposure and altered mRNA expression was found for the steroidogenic genes LHCGR, aromatase, and StAR. At one year of age, mammary gland hyperplasia was observed in high dose MEHP-exposed females. In summary, late gestational exposure to MEHP leads to multiple latent reproductive effects throughout murine life resulting in premature ovarian senescence and mammary hyperplasia.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Moyer
authors.forename: Mary L
authors.initials: ML
authors.lastname: Hixon
mesh_terms: D019588:Aging, Premature; D000818:Animals; D001141:Aromatase / Q000235:genetics; D002460:Cell Line; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000473:pathology; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics; D012098:Reproduction / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D010968:Plasticizers; D012333:RNA, Messenger; D011962:Receptors, FSH; D011974:Receptors, LH; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004051:Diethylhexyl Phthalate; D001141:Aromatase; C016599:mono-(2-ethylhexyl)phthalate