[en] BACKGROUND/AIMS: The ewe is increasingly being used as an animal model for pelvic floor disorders. The aim was to further characterize changes in the vaginal properties during its entire lifespan.
METHODS: Vaginal tissues were collected at different stages of reproductive life (neonatal, prepubescence, nulliparous, primiparous, multiparous, and menopausal; ≥6 ewes/group). Vaginal size, as well as active and passive biomechanics, was measured. Microscopy included thickness of glycogen, epithelium, lamina propria and muscularis thickness, densities of collagen, elastin, smooth muscle, and nerves.
RESULTS: Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. The thickness of lamina propria and muscularis increased in puberty and in nulliparous. Semi-quantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries.
CONCLUSION: The changes in the ovine vaginal wall during representative moments of her lifespan parallel those observed in women.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Hympanova, Lucie; Centre for Surgical Technologies, KU Leuven, Leuven, Belgium ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium ; Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czechia
Rynkevic, Rita; Centre for Surgical Technologies, KU Leuven, Leuven, Belgium ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium ; INEGI, Faculdade de Engenharia da Universidade do Porto, Porto, Portugal
Urbankova, Iva; Centre for Surgical Technologies, KU Leuven, Leuven, Belgium ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium ; Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czechia
BLACHER, Silvia ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
DE LANDSHEERE, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR)
Mackova, Katerina; Centre for Surgical Technologies, KU Leuven, Leuven, Belgium ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium ; Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czechia
Krofta, Ladislav; Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czechia
Deprest, Jan; Centre for Surgical Technologies, KU Leuven, Leuven, Belgium, jan.deprest@uzleuven.be ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium, jan.deprest@uzleuven.be ; Pelvic Floor Unit, University Hospitals KU Leuven, Leuven, Belgium, jan.deprest@uzleuven.be
Language :
English
Title :
Morphological and Functional Changes in the Vagina following Critical Lifespan Events in the Ewe.
DeLancey JO, Kane Low L, Miller JM, Patel DA, Tumbarello JA: Graphic integration of causal factors of pelvic floor disorders: an integrated life span model. Am J Obstet Gynecol 2008; 199: 610.e1-e5.
Deprest J, Feola A: The need for preclinical research on pelvic floor reconstruction. BJOG 2013; 120: 141-143.
Abramowitch SD, Feola A, Jallah Z, Moalli PA: Tissue mechanics, animal models, and pelvic organ prolapse: a review. Eur J Obstet Gynecol Reprod Biol 2009; 144(suppl 1):S146-S158.
Feola A, Abramowitch S, Jallah Z, Stein S, Barone W, Palcsey S, Moalli P: Deterioration in biomechanical properties of the vagina following implantation of a high-stiffness prolapse mesh. BJOG 2013; 120: 224-232.
Barberini F, Correr S, De Santis F, Motta PM: The epithelium of the rabbit vagina: a microtopographical study by light, transmission and scanning electron microscopy. Arch Histol Cytol 1991; 54: 365-378.
Ozog Y, Mazza E, De Ridder D, Deprest J: Biomechanical effects of polyglecaprone fibers in a polypropylene mesh after abdominal and rectovaginal implantation in a rabbit. Int Urogynecol J 2012; 23: 1397-1402.
Coates KW, Gibson S, Williams LE, Brady A, Abee CR, Shull BL, Kuehl TJ: The squirrel monkey as an animal model of pelvic relaxation: an evaluation of a large breeding colony. Am J Obstet Gynecol 1995; 173: 1664-1670.
Otto LN, Slayden OD, Clark AL, Brenner RM: The rhesus macaque as an animal model for pelvic organ prolapse. Am J Obstet Gynecol 2002; 186: 416-421.
Schimpf M, Tulikangas P: Evolution of the female pelvis and relationships to pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2005; 16: 315-320. 10 (SCHER) SC on H ER: Non-human primates in research and safety testing. 2009.
Urbankova I, Vdoviakova K, Rynkevic R, Sindhwani N, Deprest D, Feola A, Herijgers P, Krofta L, Deprest J: Comparative anatomy of the ovine and female pelvis. Gynecol Obstet Invest 2017; 82: 582-591.
Ulrich D, Edwards SL, Letouzey V, Su K, White JF, Rosamilia A, Gargett CE, Werkmeister JA: Regional variation in tissue composition and biomechanical properties of postmenopausal ovine and human vagina. PLoS One 2014; 9:e104972.
Feola A, Endo M, Urbankova I, Vlacil J, Deprest T, Bettin S, Klosterhalfen B, Deprest J: Host reaction to vaginally inserted collagen containing polypropylene implants in sheep. Am J Obstet Gynecol 2015; 212: 474. e1-e8.
Urbankova I, Callewaert G, Sindhwani N, Turri A, Hympanova L, Feola A, Deprest J: Transvaginal mesh insertion in the ovine model. J Vis Exp 2017.
Manodoro S, Endo M, Uvin P, Albersen M, Vlácil J, Engels A, Schmidt B, De Ridder D, Feola A, Deprest J: Graft-related complications and biaxial tensiometry following experimental vaginal implantation of flat mesh of variable dimensions. BJOG 2013; 120: 244-250.
Ulrich D, Edwards SL, Su K, White JF, Ramshaw JA, Jenkin G, Deprest J, Rosamilia A, Werkmeister JA, Gargett CE: Influence of reproductive status on tissue composition and biomechanical properties of ovine vagina. PLoS One 2014; 9:e93172.
Urbankova I, Callewaert G, Blacher S, Deprest D, Hympanova L, Feola A, De Landsheere L, Deprest J: First delivery and ovariectomy affect biomechanical and structural properties of the vagina in the ovine model. Int Urogynecol J 2018, DOI: 10.1007/s00192-017-3535-9.
Ulrich D, Edwards SL, Alexander DLJ, Rosamilia A, Werkmeister JA, Gargett CE, Letouzey V: Changes in pelvic organ prolapse mesh mechanical properties following implantation in rats. Am J Obstet Gynecol 2016; 214: 260.e1-260.e8.
Reinwald S, Burr D: Review of nonprimate, large animal models for osteoporosis research. J BONE Miner Res 2008; 23: 1353-1368.
Peiró JR, Nogueira GM, Nogueira GP, Perri SH, Cardoso D: Ovariectomy by left flank approach in prepubertal Nelore (bos indicus) heifers. Can J Vet Res 2009; 73: 237-240.
Ozog Y, Konstantinovic ML, Werbrouck E, De Ridder D, Edoardo M, Deprest J: Shrinkage and biomechanical evaluation of lightweight synthetics in a rabbit model for primary fascial repair. Int Urogynecol J 2011; 22: 1099-1108.
Jallah Z, Liang R, Feola A, Barone W, Palcsey S, Abramowitch SD, Yoshimura N, Moalli P: The impact of prolapse mesh on vaginal smooth muscle structure and function. BJOG 2016; 123: 1076-1085.
De Landsheere L, Blacher S, Munaut C, Nusgens B, Rubod C, Noel A, Foidart JM, Cosson M, Nisolle M: Changes in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse. Int Urogynecol J 2014; 25: 1673-1681.
Eyk NV, Allen L, Giesbrecht E, Jamieson MA, Kives S, Morris M, Ornstein M, Fleming N: Pediatric vulvovaginal disorders: a diagnostic approach and review of the literature. J Obstet Gynaecol Can 2009; 31: 850-862.
Pendergrass L, Reeves CA, Belovicz MW, Molter DJ, White JH: The shape and dimensions of the human vagina as seen in threedimensional vinyl polysiloxane casts. Gynecol Obstet Invest 1996; 42: 178-182.
Barnhart KT, Izquierdo A, Pretorius ES, Shera DM, Shabbout M, Shaunik A: Baseline dimensions of the human vagina. Hum Reprod 2006; 21: 1618-1622.
Kershaw CM, Khalid M, McGowan MR, Ingram K, Leethongdee S, Wax G, Scaramuzzi RJ: The anatomy of the sheep cervix and its influence on the transcervical passage of an inseminating pipette into the uterine lumen. Theriogenology 2005; 64: 1225-1235.
Tan JS, Lukacz ES, Menefee SA, Luber KM, Albo ME, Nager CW: Determinants of vaginal length. Am J Obstet Gynecol 2006; 195: 1846-1850.
Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA: Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol 2016; 215: 704-711.
Eberhart R, Chuong C, Zimmern P: Exploring biomechanical methods to study the human vaginal wall. Neurourol Urodyn 2017; 36: 499-506.
Lopez SO, Eberhart RC, Zimmern PE, Chuong CJ: Influence of body mass index on the biomechanical properties of the human prolapsed anterior vaginal wall. Int Urogynecol J 2015; 26: 519-525.
Goh JT: Biomechanical properties of prolapsed vaginal tissue in pre-and postmenopausal women. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13: 76-79.
Young N, Rosamilia A, Arkwright J, Lee J, Davies-Tuck M, Melendez J, Werkmeister J, Gargett CE: Vaginal wall weakness in parous ewes: a potential preclinical model of pelvic organ prolapse. Int Urogynecol J 2017; 28: 999-1004.
Emmerson S, Young N, Rosamilia A, Parkinson L, Edwards SL, Vashi AV, Davies-Tuck M, White J, Elgass K, Lo C, Arkwright J, Werkmeister JA, Gargett CE: Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: Implication for pelvic organ prolapse. Sci Rep 2017; 7: 45709.
De Landsheere L, Munaut C, Nusgens B, Maillard C, Rubod C, Nisolle M, Cosson M, Foidart JM: Histology of the vaginal wall in women with pelvic organ prolapse: a literature review. Int Urogynecol J 2013; 24: 2011-2020.
Vetuschi A, D'Alfonso A, Sferra R, Zanelli D, Pompili S, Patacchiola F, Gaudio E, Carta G: Changes in muscularis propria of anterior vaginal wall in women with pelvic organ prolapse. Eur J Histochem 2016; 60: 2604.
Kerkhof MH, Ruiz-Zapata AM, Bril H, Bleeker MC, Belien JA, Stoop R, Helder MN: Changes in tissue composition of the vaginal wall of premenopausal women with prolapse. Am J Obstet Gynecol 2013; 210: 168.e1-e9.
Jackson S, James M, Abrams P: The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence. BJOG 2002; 109: 339-344.
Fratzl P: Collagen: Structure and Mechanics. Boston, Springer, 2008.
Rynkevic R, Martins P, Hympanova L, Almeida H, Fernandes AA, Deprest J: Biomechanical and morphological properties of the multiparous ovine vagina and effect of subsequent pregnancy. J Biomech 2017; 57: 94-102.
Song YB, Hwang K, Kim DJ, Han SH: Innervation of vagina: Microdissection and immunohistochemical study. J Sex Marital Ther 2009; 35: 144-153.
Traish AM, Botchevar E, Kim NN: Biochemical factors modulating female genital sexual arousal physiology. J Sex Med 2010; 7: 2925-2946.
Basha M, Labelle EF, Northington GM, Wang T, Wein AJ, Chacko S, Ückert S, Ehlers V, Nüser V, Oelke M, Kauffels W, Scheller, F, Jonas U: Functional significance of muscarinic receptor expression within the proximal and distal rat vagina. Am J Physiol Regul Integr Comp Physiol 2009; 297:R1486-R1493.
Northington GM, Basha M, Arya LA, Wein AJ, Chacko S: Contractile response of human anterior vaginal muscularis in women with and without pelvic organ prolapse. Reprod Sci 2011; 18: 296-303.
Uckert S, Ehlers V, Nüser V, Oelke M, Kauffels W, Scheller F, Jonas U: In vitro functional responses of isolated human vaginal tissue to selective phosphodiesterase inhibitors. World J Urol 2005; 23: 398-404.
Endo M, Urbankova I, Vlacil J, Sengupta S, Deprest T, Klosterhalfen B, Feola A, Deprest J: Cross-linked xenogenic collagen implantation in the sheep model for vaginal surgery. Gynecol Surg 2015; 12: 113-122.
Feola A, Moalli P, Alperin M, Duerr R, Gandley RE, Abramowitch S: Impact of pregnancy and vaginal delivery on the passive and active mechanics of the rat vagina. Ann Biomed Eng 2011; 39: 549-558.
Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA: Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol 2002; 187: 56-63.
Mustonen E, Taponen S, Andersson M, Sukura A, Katila T, Taponen J: Fertility and growth of nulliparous ewes after feeding red clover silage with high phyto-oestrogen concentrations. Animal 2014; 8: 1699-1705.
Barron AM, Cake M, Verdile G, Martins RN: Ovariectomy and 17 beta-estradiol replacement do not alter beta-amyloid levels in sheep brain. Endocrinology 2009; 150: 3228-3236.
Turner A, Mallinckrodt C, Alvis M, Bryant H: Dual-energy X-ray absorptiometry in sheep: experiences with in vivo and ex vivo studies. Bone 1995; 17(4 suppl):S381-S387.
Oheim R, Amling M, Ignatius A, Pogoda P: Large animal model for osteoporosis in humans: the ewe. Eur Cell Mater 2012; 24: 372-385.
MacLeay JM, Olson JD, Enns RM, Les CM, Toth CA, Wheeler DL, Turner AS: Dietaryinduced metabolic acidosis decreases bone mineral density in mature ovariectomized ewes. Calcif Tissue Int 2004; 75: 431-437.
Sigrist IM, Gerhardt C, Alini M, Schneider E, Egermann M: The long-term effects of ovariectomy on bone metabolism in sheep. J Bone Miner Metab 2007; 25: 28-35.
Kerbage Y, Giraudet G, Rubod C, Garabedian C, Rivaux G, Cosson M: Feasibility and benefits of the ewe as a model for vaginal surgery training. Int Urogynecol J 2017; 28: 1573-1577.
Mansoor A, Curinier S, Campagne-Loiseau S, Platteeuw L, Jacquetin B, Rabischong B: Development of an ovine model for training in vaginal surgery for pelvic organ prolapse. Int Urogynecol J 2017; 28: 1595-1597.
De Tayrac R, Alves A, Thérin M: Collagencoated vs noncoated low-weight polypropylene meshes in a sheep model for vaginal surgery. a pilot study. Int Urogynecol J Pelvic Floor Dysfunct 2007; 18: 513-520.
Hympánová L, Rynkevic R, Román S, Mori da Cunha MGMC, Mazza E, Zündel M, Urbánková I, Gallego MR, Vange J, Callewaert G, Chapple C, MacNeil S, Deprest J: Assessment of electrospun and ultra-lightweight polypropylene meshes in the sheep model for vaginal surgery. Eur Urol Focus 2018; pii: S2405-4569(18)30190-1.