Repeated birth injuries lead to long-term pelvic floor muscle dysfunction in the preclinical rat model

• Published in: American journal of obstetrics and gynecology 2024-08
• Main Authors: Duran, Pamela, Zelus, Emma I., Burnett, Lindsey A., Christman, Karen L., Alperin, Marianna
• Format: Article
• Language: English
• Subjects: birth injury; multiparity; muscle dysfunction; pelvic floor muscles; regeneration
• ISSN: 0002-9378; 1097-6868; 1097-6868
• DOI: 10.1016/j.ajog.2024.08.036

Vaginal childbirth is a key risk factor for pelvic floor muscle injury and dysfunction, and subsequent pelvic floor disorders. Multiparity further exacerbates these risks. Using the rat model, validated for the studies of the human pelvic floor muscles, we have previously identified that a single simulated birth injury results in pelvic floor muscle atrophy and fibrosis. To test the hypothesis that multiple birth injuries would further overwhelm the muscle regenerative capacity, leading to functionally relevant pathological alterations long-term. Sprague-Dawley rats underwent simulated birth injury and were allowed to recover for 8 weeks before undergoing additional birth injury. Animals were sacrificed at acute (3 and 7 days postinjury), subacute (21, 28, and 35 days postinjury), and long-term (8 and 12 weeks postinjury) time points post second injury (N=3–8/time point), and the pubocaudalis portion of the rat levator ani complex was harvested to assess the impact of repeated birth injuries on muscle mechanical and histomorphological properties. The accompanying transcriptional changes were assessed by a customized NanoString panel. Uninjured animals were used as controls. Data with a parametric distribution were analyzed by a 2-way analysis of variance followed by post hoc pairwise comparisons using Tukey’s or Sidak’s tests; nonparametrically distributed data were compared with Kruskal-Wallis test followed by pairwise comparisons with Dunn’s test. Data, analyzed using GraphPad Prism v8.0, San Diego, CA, are presented as mean ± standard error of the mean or median (range). Following the first simulated birth injury, active muscle force decreased acutely relative to uninjured controls (12.9±0.9 vs 25.98±2.1 g/mm2, P.99). Similarly, precipitous decrease in active force was observed immediately after repeated birth injury (18.07±1.2 vs 25.98±2.1 g/mm2, P