The four latent transforming growth factor-beta (TGF-beta) binding proteins LTBP1-4 are extracellular matrix associated proteins playing a critical role in the activation of TGF-beta. 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 (Ltbp1 Delta Ex5), or exon 8 (Ltbp1 Delta Ex8). While the Ltbp1L knockout and the Ltbp1 Delta Ex8 are perinatal lethal and die of cardiovascular abnormalities, the Ltbp1 Delta Ex5 is viable because it expresses a short form of Ltbp1L that lacks 55 amino acids (Delta 55 variant of Ltbp1) formed by splicing out exon 5, while lacking the Ltbp1S variant. Since only the Ltbp1 Delta Ex5 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 Ltbp1 Delta Ex5 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). (C) 2016 Elsevier Inc. All rights reserved.