Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Front Endocrinol (Lausanne). 2023 Jun 22;14:1119599. doi: 10.3389/fendo.2023.1119599. eCollection 2023.
Menopause is a risk factor for pelvic organ prolapse (POP) and is frequently associated with diminished vaginal wall support. To uncover relevant molecular mechanisms and provide potential therapeutic targets, we evaluated changes in the transcriptome and metabolome of the vaginal wall in ovariectomized rats to identify important molecular changes.
Sixteen adult female Sprague-Dawley rats were randomly assigned to either the control or menopause group. Seven months after the operation, hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to observe changes in the rat vaginal wall structure. Differentially expressed genes (DEGs) and metabolites (DEMs) in the vaginal wall were detected by RNA-sequencing and LC-MS, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs and DEMs were performed.
We verified that long-term menopause causes vaginal wall injury by H&E and Masson trichrome staining. From the multiomics analyses, 20,669 genes and 2193 metabolites were identified. Compared with the control group, 3255 DEGs were found in the vaginal wall of long-term menopausal rats. Bioinformatics analysis showed that the DEGs were mainly enriched in mechanistic pathways, including cell-cell junction, extracellular matrix, muscle tissue developments, the PI3K-Akt signaling pathway, the MAPK signaling pathway, tight junctions and the Wnt signaling pathway. Additionally, 313 DEMs were found, and they consisted mostly of amino acids and their metabolites. DEMs were also enriched in mechanistic pathways, such as glycine, serine and threonine metabolism, glycerophospholipid metabolism, gap junctions and ferroptosis. Coexpression analysis of DEGs and DEMs revealed that biosynthesis of amino acids (isocitric acid and ) and glycerophospholipid metabolism (1-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine and ) are critical metabolic pathways, suggesting that POP induced by menopause may be associated with the regulation of these processes.
The findings showed that long-term menopause greatly exacerbated vaginal wall support injury by decreasing the biosynthesis of amino acids and interfering with glycerophospholipid metabolism, which may result in POP. This study not only clarified that long-term menopause exacerbates damage to the vaginal wall but also provided insight into the potential molecular mechanisms by which long-term menopause induces POP.
绝经是盆腔器官脱垂（POP）的一个风险因素，常伴有阴道壁支撑力减弱。为了揭示相关的分子机制并提供潜在的治疗靶点，我们评估了去卵巢大鼠阴道壁的转录组和代谢组的变化，以确定重要的分子变化。
将 16 只成年雌性 Sprague-Dawley 大鼠随机分为对照组和绝经组。手术后 7 个月，用苏木精-伊红（H&E）染色和 Masson 三色染色观察大鼠阴道壁结构的变化。通过 RNA-seq 和 LC-MS 分别检测阴道壁中的差异表达基因（DEGs）和差异代谢物（DEMs）。对 DEGs 和 DEMs 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。
我们通过 H&E 和 Masson 三色染色证实长期绝经会导致阴道壁损伤。通过多组学分析，共鉴定出 20669 个基因和 2193 个代谢物。与对照组相比，长期绝经大鼠阴道壁中发现 3255 个 DEGs。生物信息学分析表明，DEGs 主要富集在机械途径中，包括细胞-细胞连接、细胞外基质、肌肉组织发育、PI3K-Akt 信号通路、MAPK 信号通路、紧密连接和 Wnt 信号通路。此外，还发现了 313 个 DEMs，它们主要由氨基酸及其代谢物组成。DEMs 也富集在机械途径中，如甘氨酸、丝氨酸和苏氨酸代谢、甘油磷脂代谢、缝隙连接和铁死亡。DEGs 和 DEMs 的共表达分析表明，氨基酸（异柠檬酸和）和甘油磷脂代谢（1-（9Z-十六烯酰基）-sn-甘油-3-磷酸胆碱和）的生物合成是关键代谢途径，提示绝经引起的 POP 可能与这些过程的调节有关。
研究结果表明，长期绝经通过减少氨基酸的生物合成和干扰甘油磷脂代谢，极大地加重了阴道壁的支撑损伤，可能导致 POP。本研究不仅阐明了长期绝经加重阴道壁损伤，而且为长期绝经引起 POP 的潜在分子机制提供了新的见解。
