Long-term effects of vaginal surgery and endogenous ovarian hormones on the vagina and bladder

Author:

Ho Tam1ORCID,Zhang Jerry1,Wen Yan2,Guo Song1,Dobberfuhl Amy Diane2ORCID,Chen Bertha1

Affiliation:

1. Department of Obstetrics and Gynecology, Stanford University , Palo Alto, CA 94304 , United States

2. Department of Urology, Stanford University , Palo Alto, CA 94304 , United States

Abstract

Abstract Background Surgery is a common treatment for pelvic organ prolapse (POP); however, risk of recurrence and reoperation is high, resulting in a negative impact on quality of life and sexual function. Aim To examine the long-term effects of POP surgery and endogenous circulating ovarian hormones on the vagina and bladder. Methods Our animal model simulated surgical injury of the vagina and bladder during POP surgery. Female Rowett nude rats were divided into 4 groups: intact control (IC), vaginal surgery only (V), ovariectomy only (O), and ovariectomy + vaginal surgery (OV). Rats were euthanized 10 weeks postsurgery. Proximal vagina and bladder dome/trigone underwent (1) organ bath myography to assess smooth muscle contractility; (2) real-time quantitative polymerase chain reaction to quantify mRNA expression of elastin, collagen I and III, and PGP9.5 (protein gene product 9.5); (3) enzyme-linked immunosorbent assay for protein quantification of elastin and collagen I and III; and (4) hematoxylin-eosin/immunohistochemistry staining. Outcomes The primary outcome was tissue contractility as measured by organ bath myography. Secondary outcomes included gene and protein expression of collagen I and III and elastin. Results O and OV showed reduced vaginal wall contractility vs IC and V (P < .002). Bladder dome and trigone displayed different contractile patterns, with significant differences between O and OV (P < .05), suggesting a negative effect from surgery rather than ovariectomy. OV demonstrated consistent reductions in contractility and elastin/collagen protein expression for the vagina and bladder vs IC. V had similar contractility and increased collagen I expression vs IC, suggesting a protective effect of ovarian hormones. Vaginal epithelium thinning was confirmed in the ovariectomized groups (P = .001), although there was no statistical significance in muscularis thinning with surgery or ovariectomy. O, V, and OV showed significant downregulation of PGP9.5 mRNA expression vs IC. Clinical Translation These data allow researchers to gain insights into the long-term effects of surgery and deprivation of ovarian hormones. Future studies can use this animal model to investigate other mechanisms that may affect long-term tissue changes due to surgical intervention. Strengths and Limitations Major strengths are long-term data on the effects of POP surgery and development of an animal model for future studies. However, the animal model limits our ability to extrapolate to humans, where tissue healing is modulated by many factors. Conclusion Our animal model provides evidence that ovarian hormone deprivation and POP surgery result in negative long-term effects on tissue function and extracellular matrix.

Funder

National Institutes of Health

California Institute for Regenerative Medicine

Publisher

Oxford University Press (OUP)

Subject

Behavioral Neuroscience,Urology,Dermatology,Reproductive Medicine,Endocrinology,Endocrinology, Diabetes and Metabolism,Psychiatry and Mental health

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