Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu 18618-687, Brazil.
Postgraduate Program in Materials Science and Technology (POSMAT), School of Sciences, São Paulo State University (UNESP), Bauru 17033-360, Brazil.
Int J Mol Sci. 2022 Oct 25;23(21):12864. doi: 10.3390/ijms232112864.
Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.
妊娠期糖尿病（GDM）被认为是预测 2 型糖尿病和盆底肌肉疾病（包括尿失禁和泌尿生殖功能障碍）等并发症的“机会之窗”。转化研究报告称，盆底肌肉疾病是由 GDM 引起的盆底肌肉和腹直肌（RAM）的肌肉病（GDiM）引起的。我们现在描述了从 GDM 和非 GDM 女性剖宫产获得的 RAM 的转录组谱，这些女性有或没有妊娠特异性尿失禁（PSUI）。我们总共鉴定了 650 个基因，通过将三个对照组与 GDM 伴 PSUI 组（GDiM）进行比较，定义了差异表达的基因。富集分析表明，GDM 伴 PSUI 与肌肉结构和肌肉蛋白合成相关的基因表达减少、肌肉纤维缓解肌肉损伤的能力降低以及通过糖生成改变能量的维持和产生有关。通过 RT-PCR 验证了潜在的遗传肌肉生物标志物，并验证了它们与疾病病理生理学的关系。这些发现有助于阐明 GDiM 的分子机制，并将促进开发预防和治疗 GDM 后尿失禁等并发症的创新干预措施。
