Relationship between Partial Uterine Cervical Tissue Excision and Preterm Birth: An Experimental Animal Study
04 May 2017
09 May 2017
07 June 2017 (eFirst)
Objective To investigate whether the uterine cervix excision is associated with preterm birth in female mice.
Study Design Sexually mature female C57BL/6 mice (n = 40) were randomly divided into four groups (A, sham; B, cervical excision; C, lipopolysaccharide, 100 µg intrauterine injection; and D, cervical excision + lipopolysaccharide injection), with 10 mice per group. Three weeks after cervical excision, timed mating was performed. On gestational day 16, lipopolysaccharide was injected between the first and second horns of the right uterus near the cervix. The uterine cervix was obtained after delivery and was histologically analyzed.
Results The mean gestational period in group D was significantly lower than those in the other groups (17, 19.5, 19, and 18.2 days in groups D, A, B, and C, respectively; p = 0.034). The cervical length was shorter in the cervical excision groups (p = 0.004). The muscle-to-collagen ratio in the proximal cervix was higher in group D (p = 0.037).
Conclusion Prepregnancy cervical excision and subsequent lipopolysaccharide injection showed a high rate of preterm birth, which was higher than the known lipopolysaccharide injection related preterm birth rate. Prepregnancy cervical excision appears to have additive effects with inflammation in inducing preterm birth, which are associated with the relative muscular component amount.
This paper was partially presented at the 37th Annual Meeting of the Society for Maternal-Fetal Medicine, Las Vegas, NE, January 23–28, 2017.
This research was financially supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Science, ICT, and Future Planning (2014R1A1A1002300) and a grant from Korea University Medical Center and Anam Hospital, Seoul, Republic of Korea (grant no. K1620211). The funding source did not affect the results of this study.
- 1 Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science 2014; 345 (6198): 760-765
- 2 Svare JA, Andersen LF, Langhoff-Roos J. , et al. The relationship between prior cervical conization, cervical microbial colonization and preterm premature rupture of the membranes. Eur J Obstet Gynecol Reprod Biol 1992; 47 (01) 41-45
- 3 Jakobsson M, Gissler M, Sainio S, Paavonen J, Tapper AM. Preterm delivery after surgical treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2007; 109 (2 Pt 1): 309-313
- 4 Nøhr B, Tabor A, Frederiksen K, Kjaer SK. Loop electrosurgical excision of the cervix and the subsequent risk of preterm delivery. Acta Obstet Gynecol Scand 2007; 86 (05) 596-603
- 5 Castanon A, Landy R, Brocklehurst P. , et al; PaCT Study Group. Risk of preterm delivery with increasing depth of excision for cervical intraepithelial neoplasia in England: nested case-control study. BMJ 2014; 349: g6223 . Doi: 10.1136/bmj.g6223
- 6 Miller ES, Sakowicz A, Grobman WA. The association between cervical dysplasia, a short cervix, and preterm birth. Am J Obstet Gynecol 2015; 213 (04) 543.e1-543.e4
- 7 Conner SN, Frey HA, Cahill AG, Macones GA, Colditz GA, Tuuli MG. Loop electrosurgical excision procedure and risk of preterm birth: a systematic review and meta-analysis. Obstet Gynecol 2014; 123 (04) 752-761
- 8 Elovitz MA, Wang Z, Chien EK, Rychlik DF, Phillippe M. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4. Am J Pathol 2003; 163 (05) 2103-2111
- 9 Jordan J, Singer A, Jones III A, Shafi M. The Cervix. 2nd ed. Malden, MA: Blackwell; 2006
- 10 Danforth DN. The fibrous nature of the human cervix, and its relation to the isthmic segment in gravid and nongravid uteri. Am J Obstet Gynecol 1947; 53 (04) 541-560
- 11 Myers KM, Paskaleva AP, House M, Socrate S. Mechanical and biochemical properties of human cervical tissue. Acta Biomater 2008; 4 (01) 104-116
- 12 Vink JY, Qin S, Brock CO. , et al. A new paradigm for the role of smooth muscle cells in the human cervix. Am J Obstet Gynecol 2016; 215 (04) 478.e1-478.e11
- 13 Roddick Jr JW, Buckingham JC, Danforth DN. The muscular cervix--a cause of incompetency in pregnancy. Obstet Gynecol 1961; 17: 562-565
- 14 Buckingham JC, Buethe Jr RA, Danforth DN. Collagen-muscle ratio in clinically normal and clinically incompetent cervices. Am J Obstet Gynecol 1965; 91: 232-237
- 15 Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM. The preterm labor syndrome. Ann N Y Acad Sci 1994; 734: 414-429
- 16 Warren JE, Nelson LM, Stoddard GJ, Esplin MS, Varner MW, Silver RM. Polymorphisms in the promoter region of the interleukin-10 (IL-10) gene in women with cervical insufficiency. Am J Obstet Gynecol 2009; 201 (04) 372.e1-372.e5
- 17 Warren JE, Silver RM, Dalton J, Nelson LT, Branch DW, Porter TF. Collagen 1Alpha1 and transforming growth factor-beta polymorphisms in women with cervical insufficiency. Obstet Gynecol 2007; 110 (03) 619-624
- 18 Schlembach D, Mackay L, Shi L, Maner WL, Garfield RE, Maul H. Cervical ripening and insufficiency: from biochemical and molecular studies to in vivo clinical examination. Eur J Obstet Gynecol Reprod Biol 2009; 144 (Suppl. 01) S70-S76
- 19 Leppert PC, Yu SY, Keller S, Cerreta J, Mandl I. Decreased elastic fibers and desmosine content in incompetent cervix. Am J Obstet Gynecol 1987; 157 (05) 1134-1139
- 20 Elovitz MA, Mrinalini C. Animal models of preterm birth. Trends Endocrinol Metab 2004; 15 (10) 479-487
- 21 Phillips JB, Abbot P, Rokas A. Is preterm birth a human-specific syndrome?. Evol Med Public Health 2015; 2015 (01) 136-148
- 22 Akgul Y, Word RA, Ensign LM. , et al. Hyaluronan in cervical epithelia protects against infection-mediated preterm birth. J Clin Invest 2014; 124 (12) 5481-5489