Comparison of Morphological and Histological Characteristics of Human and Sheep: Sheep as a Potential Model for Testing Midurethral Slings in vivo

Abstract

Introduction: The sheep was evaluated as a potential model for preclinical evaluation of urethral slings in vivo based on: (1) anatomical measurements of the sheep vagina and (2) histological tissue integration and host response to polypropylene (PP) slings.

Methods: Eight female, multiparous sheep were utilized. Three of 8 animals underwent surgery mimicking human tension-free vaginal tape protocols for midurethral slings and were euthanized at 6 months. The following measurements were obtained: vaginal length, maximum vaginal width with retraction, symphysis pubis length, and distance from the pubic bone to incision. Explanted sling samples from sheep and human were stained with hematoxylin and eosin for host reaction assessment.

Results: Geometric measurements were similar between humans and sheep. Sheep vaginal anatomy allowed sling placement similar to procedures in human surgeries, and all sheep recovered without problems. Comparative histology between the sheep and human indicated similar host reaction and collagen deposition around implants, confirming suitability of the sheep model for biomaterial response assessment.

Conclusion: Sheep vaginal length is comparable to humans. Tissue integration and host response to PP slings showed chronic inflammation with rich collagen deposition around the material in both sheep and human specimens, highlighting the sheep as a potential animal model for preclinical testing of midurethral slings.

Keywords: Midurethral sling; Preclinical testing; Sheep model; Stress urinary incontinence.

Fig. 1.

Measurements of pelvic landmarks. a Schematic description of measured dimensions of the sheep vagina. b Depicts measurement of sheep vaginal length. c Measurement of pubic bone length.

Fig. 2.

Midurethral sling implantation. a Demonstration of the sheep’s preoperative positioning and the allocation of the human-sized self-retaining retractor and stays. Cystoscopy image of the urethra (b) and bladder (c). d Insertion of trocars. e Sling was inserted under the urethra through a vaginal incision before deployment. f Closure of vaginal incisions.

Fig. 3.

Harvest procedure. a Demonstration of a circular incision made around the urethra and vagina (yellow arrows). b, c Dissection was performed in the perineal region to separate the posterior vaginal wall from the rectum (white arrows). d Pubectomy was performed using a bypass lopper to expose the urethra. e Midurethral sling was detached from the pelvic bones (“B,” bladder and “V,” vagina). f Depicts explanted samples from the sheep. B, bladder; V, vagina; U, uterus; P, pubic bones.

Fig. 4.

H&E-stained explanted sling specimens. a H&E-stained sheep sling images at 6 months. b H&E-stained human sling images at 6 months. Asterisks denote sling material; red, six-pointed stars demonstrate collagen deposition in and around the sling material; yellow arrows indicate cellular infiltration in and around the sling. The scale bar is 100 μm. H&E, hematoxylin and eosin.