Pelvic floor disorders affect up to one-third of adult women. One of the most prevalent pelvic floor disorders is pelvic organ prolapse, a condition in which the pelvic organs (bladder, vagina, cervix and uterus) herniate through the vaginal opening. Up to 11% of women have surgery for pelvic organ prolapse or urinary incontinence in their lifetime and more than 225,000 inpatient surgical procedures for pelvic organ prolapse are performed per year in the United States at an estimated annual direct medical cost of over one billion dollars. Although multiple mechanisms have been hypothesized to contribute to the development of pelvic organ prolapse, none fully explain the origin and natural history of this process. Epidemiologic studies indicate that vaginal birth and aging are the two major risk factors for developing pelvic organ prolapse. During the last funding period, we used mouse models of pelvic organ prolapse and tissues from women with and without prolapse to investigate the overall hypothesis of our research program, namely that vaginal wall support is maintained by a delicate balance between the synthesis/assembly and degradation of elastic fibers in the vaginal wall. In this application, we propose to build on this solid foundation to (i understand the relative importance of elastic fiber structural integrity and protease activation in the pathogenesis of pelvic organ prolapse, (ii) investigate the contribution of a novel elastin microfibrillar protein, LTBP4, and TGF? signaling in the pathogenesis of pelvic organ prolapse, and (iii) utilize injectable nanoparticle hydrogels with or without estrogen to prevent or ameliorate development of vaginal prolapse after injury.
Women with pelvic organ prolapse suffer from urinary incontinence or retention, chronic pelvic pressure, fecal incontinence or obstruction, sexual dysfunction, social embarrassment and isolation. Experiments are proposed to understand how loss of matrix support of the pelvic organs leads to prolapse, and if connective tissues of the pelvic floor can be rescued and restored with matrix-specific therapies.
|Ripperda, Christopher M; Maldonado, Pedro Antonio; Acevedo, Jesus F et al. (2017) Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall. Menopause 24:838-849|
|Maldonado, P Antonio; Montoya, T Ignacio; Acevedo, Jesus F et al. (2017) Effects of vaginal conjugated equine estrogens and ospemifene on the rat vaginal wall and lower urinary tract. Biol Reprod 96:81-92|
|Good, Meadow M; Montoya, T Ignacio; Shi, Haolin et al. (2017) Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. PLoS One 12:e0186268|
|Chin, Kathleen; Wieslander, Cecilia; Shi, Haolin et al. (2016) Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall. PLoS One 11:e0152793|
|Alsofi, Loai; Daley, Eileen; Hornstra, Ian et al. (2016) Sex-Linked Skeletal Phenotype of Lysyl Oxidase Like-1 Mutant Mice. Calcif Tissue Int 98:172-85|
|Montoya, T Ignacio; Maldonado, P Antonio; Acevedo, Jesus F et al. (2015) Effect of vaginal or systemic estrogen on dynamics of collagen assembly in the rat vaginal wall. Biol Reprod 92:43|
|Rahn, David D; Good, Meadow M; Roshanravan, Shayzreen M et al. (2014) Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab 99:3728-36|
|Papke, Christina L; Yanagisawa, Hiromi (2014) Fibulin-4 and fibulin-5 in elastogenesis and beyond: Insights from mouse and human studies. Matrix Biol 37:142-9|
|Budatha, Madhusudhan; Silva, Simone; Montoya, Teodoro Ignacio et al. (2013) Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse. PLoS One 8:e56376|
|Balgobin, Sunil; Montoya, T Ignacio; Shi, Haolin et al. (2013) Estrogen alters remodeling of the vaginal wall after surgical injury in guinea pigs. Biol Reprod 89:138|
Showing the most recent 10 out of 20 publications