title: Sex-specific effects of low-dose gestational estradiol-17β exposure on bone development in porcine offspring.
abstract: Estrogens are important for the bone development and health. Exposure to endocrine disrupting chemicals during the early development has been shown to affect the bone phenotype later in life. Several studies have been performed in rodents, while in larger animals that are important to bridge the gap to humans there is a paucity of data. To this end, the pig as large animal model was used in the present study to assess the influence of gestational estradiol-17β (E2) exposure on the bone development of the prepubertal and adult offspring. Two low doses (0.05 and 10μg E2/kg body weight) referring to the 'acceptable daily intake' (ADI) and the 'no observed effect level' (NOEL) as stated for humans, and a high-dose (1000μg E2/kg body weight), respectively, were fed to the sows every day from insemination until delivery. In the male prepubertal offspring, the ADI dose group had a lower strength strain index (p=0.002) at the proximal tibia compared to controls, which was determined by peripheral quantitative computed tomography. Prepubertal females were not significantly affected. However, there was a higher cortical cross-sectional area (CSA) (p=0.03) and total CSA (p=0.02) at the femur midpoint in the adult female offspring of the NOEL dose group as measured by computed tomography. These effects were independent from plasma hormone concentrations (leptin, IGF1, estrogens), which remained unaltered. Overall, sex-specific effects on bone development and non-monotonic dose responses were observed. These results substantiate the high sensitivity of developing organisms to exogenous estrogens.
authors.affiliation: Physiology Weihenstephan, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, Germany; Z I E L PhD Graduate School ́Nutritional Adaptation and Epigenetic Mechanismś, Technische Universität München, Freising, Germany. Electronic address: pistek@wzw.tum.de.
authors.forename: Veronika L
authors.initials: VL
authors.lastname: Flöter
authors.affiliation: Department of Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke-Straße 17, 10315 Berlin, Germany. Electronic address: galateanu@izw-berlin.de.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Galateanu
authors.affiliation: Physiology Weihenstephan, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, Germany. Electronic address: rainer.fuerst@helmholtz-muenchen.de.
authors.forename: Rainer W
authors.initials: RW
authors.lastname: Fürst
authors.affiliation: Department of Endocrinology, University Medicine Goettingen, Robert-Koch-Str. 40, 37099 Goettingen, Germany. Electronic address: d.swuttke@verdevital.de.
authors.forename: Dana
authors.initials: D
authors.lastname: Seidlová-Wuttke
authors.affiliation: Department of Endocrinology, University Medicine Goettingen, Robert-Koch-Str. 40, 37099 Goettingen, Germany. Electronic address: w.wuttke@verdevital.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wuttke
authors.affiliation: Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria. Electronic address: Erich.Moestl@vetmeduni.ac.at.
authors.forename: Erich
authors.initials: E
authors.lastname: Möstl
authors.affiliation: Department of Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke-Straße 17, 10315 Berlin, Germany. Electronic address: hildebrandt@izw-berlin.de.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Hildebrandt
authors.affiliation: Physiology Weihenstephan, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, Germany. Electronic address: seu@ethz.ch.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ulbrich
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005269:Femur / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D012737:Sex Factors; D013552:Swine; D013977:Tibia / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors; D004958:Estradiol
keywords: Bone; Development; Epigenetic; Estradiol; Low-dose; Pig