Wang Yuan, Jiang Jun, Jiang Rui
Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Department of Thyroid Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
J Sex Med. 2025 Jun 3;22(6):993-1005. doi: 10.1093/jsxmed/qdaf081.
Androgen deficiency is an important cause of erectile dysfunction (ED), and miRNAs are small-molecule RNAs with multiple biological functions. However, whether androgen deficiency affects erectile function by regulating miRNAs is unknown.
The aim of the study was to investigate the differential expression of key miRNAs in the penile corpus cavernosum of castrated rats and the relationship between these miRNAs and erectile function.
The expression of key miRNAs in the penile corpus cavernosum of sham-operated, castration-operated, and post-castration testosterone replacement-treated rats was detected via high-throughput sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify significantly up-regulated and down-regulated miRNAs in the penile corpus cavernosum of castrated rats, functional assays and prediction and validation of target genes were performed for key miRNAs, and the relationships between the expression of key microRNAs and maximum intracavernous pressure/mean arterial pressure ratio (ICPmax/MAP) were examined.
Significant up-regulation of miR-200a-3p in the penile corpus cavernosum of castrated rats leads to ED by activating the RhoA/Rho-kinase signaling pathway and inhibiting p-eNOS/eNOS.
Among these miRNAs, the expression of miR-200a-3p was significantly greater in the penile corpus cavernosum of the cast group (50.67 ± 6.91) than in that of the sham group (1.00 ± 0.09) and the cast+T group (2.07 ± 0.35) (P < 0.05). Dlc1 and p-eNOS/eNOS in the penile corpus cavernosum of the cast group were significantly lower than those of the sham and cast+T groups (P < 0.05). The over-expression of miR-200a-3p significantly inhibited the expression of Dlc1 and decreased p-eNOS/eNOS and ICPmax/MAP (P < 0.05). Inhibition of miR-200a-3p significantly up-regulated the expression of Dlc1 and elevated the ICPmax/MAP (P < 0.05).
Inhibition of miR-200a-3p expression and function in the penile corpus cavernosum may be a potential treatment for ED due to androgen deficiency.
This study revealed that miR-200a-3p can lead to ED by affecting the RhoA/Rho-kinase and eNOS/NO signaling pathways. However, the specific mechanism of miR-200a-3prole in ED needs to be further investigated.
Significant up-regulation of miR-200a-3p in the penile corpus cavernosum of castrated rats inhibited Dlc1 expression, which activated the RhoA/Rho-kinase signaling pathway in smooth muscle cells and inhibited p-eNOS/eNOS in endothelial cells to suppress erectile function. Inhibiting endogenous miR-200a-3p in the penile corpus cavernosum of castrated rats may improve erectile function.
雄激素缺乏是勃起功能障碍（ED）的重要原因，而微小RNA（miRNA）是具有多种生物学功能的小分子RNA。然而，雄激素缺乏是否通过调节miRNA影响勃起功能尚不清楚。
本研究旨在探讨去势大鼠阴茎海绵体中关键miRNA的差异表达及其与勃起功能的关系。
通过高通量测序检测假手术、去势手术及去势后睾酮替代治疗大鼠阴茎海绵体中关键miRNA的表达。进行基因本体论和京都基因与基因组百科全书通路富集分析，以鉴定去势大鼠阴茎海绵体中显著上调和下调的miRNA，对关键miRNA进行功能测定以及靶基因预测和验证，并检测关键微小RNA表达与海绵体内最大压力/平均动脉压比值（ICPmax/MAP）之间的关系。
去势大鼠阴茎海绵体中miR-200a-3p的显著上调通过激活RhoA/ Rho激酶信号通路并抑制p-eNOS/eNOS导致勃起功能障碍。
在这些miRNA中，去势组阴茎海绵体中miR-200a-3p的表达（50.67±6.91）显著高于假手术组（1.00±0.09）和去势+睾酮组（2.07±0.35）（P<0.05）。去势组阴茎海绵体中的Dlc1和p-eNOS/eNOS显著低于假手术组和去势+睾酮组（P<0.05）。miR-200a-3p的过表达显著抑制Dlc1的表达，并降低p-eNOS/eNOS和ICPmax/MAP（P<0.05）。抑制miR-200a-3p可显著上调Dlc1的表达并提高ICPmax/MAP（P<0.05）。
抑制阴茎海绵体中miR-200a-3p的表达和功能可能是治疗雄激素缺乏所致勃起功能障碍的潜在方法。
本研究揭示了miR-200a-3p可通过影响RhoA/Rho激酶和eNOS/NO信号通路导致勃起功能障碍。然而，miR-200a-3p在勃起功能障碍中的具体作用机制仍需进一步研究。
去势大鼠阴茎海绵体中miR-200a-3p的显著上调抑制了Dlc1的表达，从而激活了平滑肌细胞中的RhoA/Rho激酶信号通路，并抑制了内皮细胞中的p-eNOS/eNOS，进而抑制勃起功能。抑制去势大鼠阴茎海绵体内源性miR-200a-3p可能改善勃起功能。
