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Postpartum cervical repair in mice: a morphological characterization and potential role for angiogenic factors

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Abstract

The cervix undergoes marked mechanical trauma during delivery of the baby at birth. As such, a timely and complete tissue repair postpartum is necessary to prevent obstetrical complications, such as cervicitis, ectropion, hemorrhage, repeated miscarriages or abortions and possibly preterm labor and malignancies. However, our knowledge of normal cervical repair is currently incomplete and factors that influence repair are unclear. Here, we characterize the morphological and angiogenic profile of postpartum repair in mice cervix during the first 48 h of postpartum. The key findings presented here are: (1) cervical epithelial folds and size are diminished during the first 48 h of postpartum repair, (2) hypoxic inducible factor 1a, vascular endothelial growth factor (VEGF), and VEGF receptor 1 expression are pronounced early in postpartum cervical repair, and (3) VEGF receptor 2 gene and protein expressions are variable. We conclude that postpartum cervical repair involves gross and microscopic changes and is linked to expression of angiogenic factors. Future studies will assess the suitability of these factors, identified in the present study, as potential markers for determining the phase of postpartum cervical repair in obstetrical complications, such as cervical lacerations.

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References

  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular biology of the cell. Garland Science, New York, pp 1417–1482

    Google Scholar 

  • Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H (2009) The role of vascular endothelial growth factor in wound healing. J Surg Res 15:347–358

    Article  Google Scholar 

  • Bauer M, Mazza E, Jabareen M, Sultan L, Bajka M, Lang U, Zimmermann R, Holzapfel GA (2009) Assessment of the in vivo biomechanical properties of the human uterine cervix in pregnancy using the aspiration test a feasibility study. Eur J Obstet Gynecol 144S:S77–S81

    Article  Google Scholar 

  • Donnelly S, Nguyen BT, Rhyne S, Estes J, Jesmin S, Mowa CN (2013) Vascular endothelial growth factor induces growth of the uterine cervix and immune cell recruitment in mice. J Endocrinol 217:83–94

    Article  CAS  PubMed  Google Scholar 

  • Eming SA, Krieg T (2006) Molecular mechanisms of VEGF-A action during tissue repair. J Invest Dermatol 11:79–86

    Article  CAS  Google Scholar 

  • Fahmy K, el-Gazar A, Sammour M, Nosair M, Salem A (1991) Postpartum colposcopy of the cervix injury and healing. Int J Gynaecol Obstet 34:133–137

    Article  CAS  PubMed  Google Scholar 

  • Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, Bunting S, Steinmetz HG, Gurtner GC (2004) Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 164:1935–1947

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gariboldi MB, Ravizza R, Monti E (2010) The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells. Biochem Pharmacol 80:455–462

    Article  CAS  PubMed  Google Scholar 

  • Ge X, Zhao L, He L, Chen W, Li X (2012) Vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1/KDR) protects HEK293 cells against CoCl2-induced hypoxic toxicity. Cell Biochem Funct 30:151–157

    Article  CAS  PubMed  Google Scholar 

  • Glaser-Gabay L, Raiter A, Battler A, Hardy B (2011) Endothelial cell surface vimentin binding peptide induces angiogenesis under hypoxic/ischemic conditions. Microvasc Res 82:221–226

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez JM, Xu H, Chai J, Ofori E, Elovitz MA (2009) Preterm and term cervical ripening in CD1 mice (Mus musculus): similar or divergent molecular mechanisms? Biol Reprod 81:1226–1232

    Article  CAS  PubMed  Google Scholar 

  • Hefland BT, Mendez MG, Murthy SN, Shumaker DK, Grin B, Mahammad S, Aebi U, Wedig T, Wu YI, Hahn KM, Inagaki M, Herrmann H, Goldman RD (2011) Vimentin organization modulates the formation of lamellipodia. Mol Biol Cell 22:1274–1289

    Article  Google Scholar 

  • Kim TR, Moon JH, Lee HM, Cho EW, Paik SG, Kim IG (2009) SM22alpha inhibits cell proliferation and protects against anticancer drugs and gamma-radiation in HepG2 cells: involvement of metallothioneins. FEBS Lett 583:3356–3362

    Article  CAS  PubMed  Google Scholar 

  • Kim TR, Cho EW, Paik SG, Kim IG (2012) Hypoxia-induced SM22α in A549 cells activates the IGF1R/PI3K/Akt pathway, conferring cellular resistance against chemo-and radiation therapy. FEBS Lett 586:303–309

    Article  CAS  PubMed  Google Scholar 

  • Lui T, Guevara OE, Warburton RR, Hill NS, Gaestel M, Kayyali US (2010) Regulation of vimentin intermediate filaments in endothelial cells by hypoxia. Am J Physiol Cell Physiol 299:C363–C373

    Article  Google Scholar 

  • Mahendroo M (2012) Cervical remodeling in term and preterm birth: insights from an animal model. Reproduction 143:429–438

    Article  CAS  PubMed  Google Scholar 

  • Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia inducible factors and the response to hypoxic stress. Mol Cell 40:294–309

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mowa CN, Jesmin S, Sakuma I, Usip S, Togashi H, Yoshioka M, Hattori Y, Papka R (2004) Characterization of vascular endothelial growth factor (VEGF) in the uterine cervix over pregnancy: effects of denervation and implications for cervical ripening. J Histochem Cytochem 52:1665–1674

    Article  CAS  PubMed  Google Scholar 

  • Mowa CN, Hoch R, Montavon CL, Jesmin S, Hindman G, Hou G (2008a) Estrogen enhances wound healing in the penis of rats. Biomed Res 29:267–270

    Article  CAS  PubMed  Google Scholar 

  • Mowa CN, Li T, Jesmin S, Folkesson HG, Usip SE, Papka RE, Hou G (2008b) Delineation of VEGF-regulated genes and functions in the cervix of pregnant rodents by DNA microarray analysis. Reprod Biol Endocrinol 6:1–10

    Article  Google Scholar 

  • Nguyen BT, Minkiewicz V, McCabe E, Cecile J, Mowa CN (2012) Vascular endothelial growth factor induces mRNA expression of pro-inflammatory factors in the uterine cervix of mice. Biomed Res 33:363–372

    Article  CAS  PubMed  Google Scholar 

  • Piecewicz SM, Pandey A, Roy B, Xiang SH, Zetter BR, Sengupta S (2012) Insulin-like growth factors promote vasculogenesis in embryonic stem cells. PLoS ONE 7:e32191

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Read CP, Word RA, Ruschenisky MA, Timmons BC, Mahendroo M (2007) Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice. Reproduction 134:327–340

    Article  CAS  PubMed  Google Scholar 

  • Rogel MR, Soni PN, Troken JR, Sitikov A, Trejo HE, Ridge KM (2011) Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells. FASEB J 25:3873–3883

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Roskoski R Jr (2007) Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol 62:179–213

    Article  PubMed  Google Scholar 

  • Semenza GL (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology 19:176–182

    Article  CAS  PubMed  Google Scholar 

  • Stuttfield E, Ballmer-Hofer K (2009) Structure and function of VEGF receptors. Life 6:915–922

    Google Scholar 

  • Timmons BC, Mahendroo M (2007) Process regulating cervical ripening differ from cervical dilation and postpartum repair: insights from gene expression studies. Reprod Sci 14:53–62

    Article  CAS  PubMed  Google Scholar 

  • Timmons BC, Fairhurst AM, Mahendroo M (2009) Temporal changes in myeloid cells in the cervix during pregnancy and parturition. J Immunol 182:2700–2707

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Timmons BC, Akins M, Mahendroo M (2010) Cervical remodeling during pregnancy and parturition. Trends Endocrinol Metab 21:353–361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Word RA, Li XH, Hnat M, Carrick K (2007) Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med 25:69–79

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Funding for the present study was provided by the College of Arts and Sciences, Appalachian State University, Boone, NC, USA.

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Authors and Affiliations

  1. The Department of Biology, Appalachian State University, 572 Rivers Street, P.O. Box 32027, Boone, NC, 28608, USA

    Robert Stanley, Takako Ohashi & Chishimba Mowa

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  1. Robert Stanley
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  2. Takako Ohashi
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  3. Chishimba Mowa
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Correspondence to Chishimba Mowa.

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Stanley, R., Ohashi, T. & Mowa, C. Postpartum cervical repair in mice: a morphological characterization and potential role for angiogenic factors. Cell Tissue Res 362, 253–263 (2015). https://doi.org/10.1007/s00441-015-2184-x

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  • DOI: https://doi.org/10.1007/s00441-015-2184-x

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