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Pregnancy with and without birth trauma modulates the gene expression of proteins involved in elastic fiber homeostasis in the rat vagina

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DOI: 10.4236/ojog.2013.38108    2,903 Downloads   4,731 Views   Citations

ABSTRACT

Objectives: Elastic fibers have been linked to the pathogenesis of pelvic organ prolapse. This study used a rat model to examine the effect of mode of delivery on the gene expression of proteins involved in elastic fiber homeostasis. Methods: 38 Sprague-Dawley rats were separated as follows: virgin rats after simulated vaginal delivery, groups A (n = 5) and B (n = 5); pregnant rats after spontaneous vaginal delivery, groups C (n = 5) and D (n = 5); pregnant rats after cesarean delivery, groups E (n = 6) and F (n = 5). Groups A, C and E were sacrificed 2 days after the intervention, groups B, D and F were sacrificed 14 days after the intervention. 7 virgin rats served as controls. Vaginal tissue was harvested for RNA extraction and cDNA conversion. The mRNA expression for lysyl oxidase like 1 (LOXL-1), tropoelastin and fibulin 5 (FBLN 5) was quantified via real-time reverse transcriptase polymerase chain reaction using the 2-ΔΔCt method; β-actin was selected as the reference gene. Results: Postpartum day two we observed an up-regulation in the relative mRNA expression of LOXL-1, FBLN 5 and Tropoelastin in all groups compared to controls. In lower vaginal tissue the up-regulation decreased uniformly from postpartum day two to postpartum day fourteen. However, the relative mRNA expression of the target genes in upper vaginal tissue persisted at postpartum day fourteen in the SpVD and CD cohort. Conclusions: Vaginal trauma, whether as a result of spontaneous vaginal delivery or simulated vaginal delivery, resulted in the upregulation of genes involved in elastic fiber homeostasis. In addition, pregnancy and parturition, in the absence of direct vaginal trauma, also resulted in the upregulation of these genes. Our findings leave open the possibility that alterations in elastic fiber homeostasis occurring during pregnancy, regardless of mode of delivery, may play a role in the pathogenesis of POP.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Downing, K. , Strube, F. , Mikhail, M. and DiSanto, M. (2013) Pregnancy with and without birth trauma modulates the gene expression of proteins involved in elastic fiber homeostasis in the rat vagina. Open Journal of Obstetrics and Gynecology, 3, 603-608. doi: 10.4236/ojog.2013.38108.

References

[1] Nygaard, I., Barber, M.D., Burgio, K.L., et al. (2008) Prevalence of symptomatic pelvic floor disorders in US women. The journal of the American Medical Association, 300, 1311-1316.
http://dx.doi.org/10.1001/jama.300.11.1311
[2] Smith, F.J., Holman, C.D., Moorin, R.E. and Tsokos, N. (2010) Lifetime risk of undergoing surgery for pelvic organ prolapse. Obstetrics and Gynecology, 116, 1096-1100.
http://dx.doi.org/10.1097/AOG.0b013e3181f73729
[3] Subak, L.L., Waetjen, L.E., van den Eeden, S., Thom, D.H., Vittinghoff, E. and Brown, J.S. (2001) Cost of pelvic organ prolapse surgery in the United States. Obstetrics and Gynecology, 98, 646-651. http://dx.doi.org/10.1016/S0029-7844(01)01472-7
[4] Bump, R.C. and Norton, P.A. (1998) Epidemiology and natural history of pelvic floor dysfunction. Obstetrics and Gynecology Clinics of North America, 25, 723-746. http://dx.doi.org/10.1016/S0889-8545(05)70039-5
[5] Handa, V.L., Blomquist, J.L., Knoepp, L.R., Hoskey, K.A., McDermott, K.C. and Munoz, A. (2011) Pelvic floor disorders 5-10 years after vaginal or cesarean childbirth. Obstetrics and Gynecology, 118, 777-784.
[6] Leijonhufvud, A., Lundholm, C., Cnattingius, S., Granath, F., Andolf, E. and Altman, D. (2011) Risks of stress urinary incontinence and pelvic organ prolapse surgery in relation to mode of childbirth. American Journal of Obstetrics and Gynecology, 204, 70e71-77.
[7] Lukacz, E.S., Lawrence, J.M., Contreras, R., Nager, C.W. and Luber, K.M. (2006) Parity, mode of delivery, and pelvic floor disorders. Obstetrics and Gynecology, 107, 1253-1260.
http://dx.doi.org/10.1097/01.AOG.0000218096.54169.34
[8] Liu, X., Zhao, Y., Gao, J., et al. (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nature Genetics, 36, 178-182. http://dx.doi.org/10.1038/ng1297
[9] Yanagisawa, H., Davis, E.C., Starcher, B.C., et al. (2002) Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature, 415, 168-171.
http://dx.doi.org/10.1038/415168a
[10] Mecham RPaD, E.C. (1994) Elastic fiber structure and assembly, Academic Press, San Diego.
[11] Wagenseil, J.E. and Mecham, R.P. (2007) New insights into elastic fiber assembly. Birth Defects Research. Part C, Embryo Today: Reviews, 81, 229-240.
[12] Starcher, B. and Percival, S. (1985) Elastin turnover in the rat uterus. Connective Tissue Research, 13, 207-215. http://dx.doi.org/10.3109/03008208509152400
[13] Woessner, J.F. and Brewer, T.H. (1963) Formation and breakdown of collagen and elastin in the human uterus during pregnancy and post-partum involution. The Biochemical Journal, 89, 75-82.
[14] Drewes, P.G., Yanagisawa, H., Starcher, B., et al. (2007) Pelvic organ prolapse in fibulin-5 knockout mice: Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. The American Journal of Pathology, 170, 578-589. http://dx.doi.org/10.2353/ajpath.2007.060662
[15] Rahn, D.D., Acevedo, J.F. and Word, R.A. (2008) Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: Potential role in the pathogenesis of pelvic organ prolapse. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 295.
http://dx.doi.org/10.1152/ajpregu.90447.2008
[16] Sandhu, K.S., Chua, R.G., Zhang, X., et al. (2009) Regional heterogeneity in expression of the sphingosine1-phosphate pathway in the female rat lower urinary tract. American Journal of Obstetrics and Gynecology, 200, 576 e571-577.
[17] Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔct method. Methods, 25, 402-408.
http://dx.doi.org/10.1006/meth.2001.1262
[18] Downing, K.T. (2012) Uterine prolapse: From antiquity to today. Obstetrics and Gynecology International, 2012. http://dx.doi.org/ 10.1155/2012/649459
[19] Rortveit, G., Daltveit, A.K., Hannestad, Y.S., Hunskaar, S. (2003) Urinary incontinence after vaginal delivery or cesarean section. The New England Journal of Medicine, 348, 900-907.
http://dx.doi.org/10.1056/NEJMoa021788
[20] Dietz, H.P. and Bennett, M.J. (2003) The effect of childbirth on pelvic organ mobility. Obstetrics and Gynecology, 102, 223-228. http://dx.doi.org/10.1016/S0029-7844(03)00476-9
[21] Nygaard, I. and Cruikshank, D.P. (2003) Should all women be offered elective cesarean delivery? Obstetrics and Gynecology, 102, 217-219. http://dx.doi.org/10.1016/S0029-7844(03)00603-3
[22] Martin, J.A., Hamilton, B.E., Ventura, S.J., et al. (2011) Births: Final data for 2009. National Vital Statistics Reports: From the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System, 60, 1-70.
[23] O’Boyle, A.L., Woodman, P.J., O’Boyle, J.D., Davis, G.D. and Swift, S.E. (2002) Pelvic organ support in nulliparous pregnant and nonpregnant women: A case control study. American Journal of Obstetrics and Gynecology, 187, 99-102. http://dx.doi.org/10.1067/mob.2002.125734
[24] Hannah, M.E., Whyte, H., Hannah, W.J., et al. (2004) Maternal outcomes at 2 years after planned cesarean section versus planned vaginal birth for breech presentation at term: The international randomized Term Breech Trial. American Journal of Obstetrics and Gynecology, 191, 917-927. http://dx.doi.org/10.1016/j.ajog.2004.08.004
[25] Thorp Jr., J.M., Norton, P.A., Wall, L.L., Kuller, J.A., Eucker, B. and Wells, E. (1999) Urinary incontinence in pregnancy and the puerperium: A prospective study. American Journal of Obstetrics and Gynecology, 181, 266-273. http://dx.doi.org/10.1016/S0002-9378(99)70546-6
[26] Buchsbaum, G.M., Chin, M., Glantz, C. and Guzick, D. (2002) Prevalence of urinary incontinence and associated risk factors in a cohort of nuns. Obstetrics and Gynecology, 100, 226-229.
http://dx.doi.org/10.1016/S0029-7844(02)02076-8
[27] Weber, A.M., Buchsbaum, G.M., Chen, B., et al. (2004) Basic science and translational research in female pelvic floor disorders: proceedings of an NIH-sponsored meeting. Neurourology and Urodynamic, 23, 288-301. http://dx.doi.org/10.1002/nau.20048
[28] Gustilo-Ashby, A.M., Lee, U., Vurbic, D., et al. (2010) The impact of cesarean delivery on pelvic floor dysfunction in lysyl oxidase like-1 knockout mice. Female Pelvic Medicine & Reconstructive Surgery, 16, 21-30.
[29] Wieslander, C.K., Marinis, S.I., Drewes, P.G., Keller, P.W., Acevedo, J.F. and Word, R.A. (2008) Regulation of elastolytic proteases in the mouse vagina during pregnancy, parturition, and puerperium. Biology of Reproduction, 78, 521-528. http://dx.doi.org/10.1095/biolreprod.107.063024
[30] Budatha, M., Roshanravan, S., Zheng, Q., et al. (2011) Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. The Journal of Clinical Investigation, 121, 2048-2059.

  
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