title: Latent TGF-β binding protein-1 deficiency decreases female fertility.
abstract: The four latent transforming growth factor-β (TGF-β) binding proteins LTBP1-4 are extracellular matrix-associated proteins playing a critical role in the activation of TGF-β. The LTBP1 gene forms two major transcript variants (i.e. Ltbp1S and Ltbp1L) that are derived from different promoters. We have previously shown the importance of LTBP1 in vivo by using three different Ltbp1 null mice that were either deleted for exons 1 and 2 (Ltbp1L knockout), exon 5 (Ltbp1ΔEx5), or exon 8 (Ltbp1ΔEx8). While the Ltbp1L knockout and the Ltbp1ΔEx8 are perinatal lethal and die of cardiovascular abnormalities, the Ltbp1ΔEx5 is viable because it expresses a short form of Ltbp1L that lacks 55 amino acids (Δ55 variant of Ltbp1) formed by splicing out exon 5, while lacking the Ltbp1S variant. Since only the Ltbp1ΔEx5 mouse is viable, we have used this model to address aspects of puberty, fertility, age-dependent reproduction, and ovary function. We report for the first time a function of LTBP1 in female reproduction. The Ltbp1ΔEx5 females showed impaired fertility associated with delayed sexual maturity (p = 0.0074) and ovarian cyst formation in females older than 40 weeks (p = 0.0204).
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany. Electronic address: eileen.dietzel@rwth-aachen.de.
authors.forename: Eileen
authors.initials: E
authors.lastname: Dietzel
authors.affiliation: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Weiskirchen
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Floehr
authors.affiliation: Department of Cell Biology, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Masahito
authors.initials: M
authors.lastname: Horiguchi
authors.affiliation: Department of Cell Biology, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Medicine, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Vesna
authors.initials: V
authors.lastname: Todorovic
authors.affiliation: Department of Cell Biology, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Medicine, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Rifkin
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany.
authors.forename: Willi
authors.initials: W
authors.lastname: Jahnen-Dechent
authors.affiliation: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University, Medical Faculty, 52074 Aachen, Germany. Electronic address: rweiskirchen@ukaachen.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004967:Estrogens / Q000097:blood; D005091:Exons; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro; D005838:Genotype; D007247:Infertility, Female / Q000235:genetics*; D053779:Latent TGF-beta Binding Proteins / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010048:Ovarian Cysts / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000097:blood
chemical_list: D002352:Carrier Proteins; D004967:Estrogens; D053779:Latent TGF-beta Binding Proteins; C509033:Ltbp1 protein, mouse; D011374:Progesterone
keywords: Female infertility; Latent binding protein; Ovarian cyst; Puberty; Transforming growth factor-β