title: Prepubertal tamoxifen treatment affects development of heifer reproductive tissues and related signaling pathways.
abstract: Prepubertal exposure of the developing ovaries and reproductive tract (RT) to estrogen or xenoestrogens can have acute and long-term consequences that compromise the reproductive performance of cattle. This research examined effects of the selective estrogen receptor modulator tamoxifen (TAM) on gene and protein abundance in prepubertal ovaries and RT, with a particular focus on signaling pathways that affect morphology. Tamoxifen was administered to Holstein heifer calves (n=8) daily (0.3mg/kg subcutaneously) from 28 to 120 d of age, when tissues were collected. Control calves (n=7) received an equal volume of excipient. Weight, gross measurements, and samples of reproductive tissues were collected, and protein and mRNA were extracted from snap-frozen samples of vagina, cervix, uterus, oviduct, ovary, and liver. Neither estradiol nor insulin-like growth factor I (IGFI) concentrations in the serum were affected by TAM treatment. Tamoxifen treatment reduced ovarian weight independently from effects on antral follicle populations, as there was no difference in visible antral follicle numbers on the day of collection. Estrogen receptor α (ESR1) and β (ESR2) mRNA, ESR1 protein, IGFI, progesterone receptor, total growth hormone receptor, WNT4, WNT5A, and WNT7A mRNA, in addition to mitogen-activated protein kinase (MAPK) and phosphorylated MAPK proteins were affected differently depending on the tissue examined. However, neither IGFI receptor mRNA nor protein abundance were affected by TAM treatment. Results indicate that reproductive development in prepubertal Holstein heifer calves is TAM-sensitive, and that bovine RT and ovarian development are supported, in part, by estrogen receptor-dependent mechanisms during the period studied here. Potential long-term consequences of such developmental disruption remain to be defined.
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061.
authors.forename: A
authors.initials: A
authors.lastname: Al Naib
authors.affiliation: Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg 24061.
authors.forename: H L M
authors.initials: HLM
authors.lastname: Tucker
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061.
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia 65211.
authors.forename: D H
authors.initials: DH
authors.lastname: Keisler
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Cellular and Molecular Biosciences Program, Auburn University, Auburn, AL 36849.
authors.forename: F F
authors.initials: FF
authors.lastname: Bartol
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061.
authors.forename: R P
authors.initials: RP
authors.lastname: Rhoads
authors.affiliation: Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg 24061.
authors.forename: R M
authors.initials: RM
authors.lastname: Akers
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061. Electronic address: rhoadsm@vt.edu.
authors.forename: M L
authors.initials: ML
authors.lastname: Rhoads
mesh_terms: D000818:Animals; D002417:Cattle / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010053:Ovary / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases
keywords: estrogen; ovary; prepubertal; uterus