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. 2022 May;50(5):3000605221100334.
doi: 10.1177/03000605221100334.

Mechanistic analysis of erectile dysfunction in a depression rat model

Zhi-Ming Hong  1 , Zi-Long Chen  1 , Jun-Long Feng  2 , Sheng-Jie Wang  1 , Jun-Feng Qiu  1 , Yang-Ling Zeng  1 , Quan Wang  1 , Ji-Sheng Wang  2
Affiliations

Mechanistic analysis of erectile dysfunction in a depression rat model

Zhi-Ming Hong et al. J Int Med Res. 2022 May.

Abstract

Objective: Most men suffering from depression have different degrees of erectile dysfunction (ED), but the relationship between depression and ED is not clear. This study explored the effect of depression on erectile function in rats and the underlying mechanism.

Methods: The potential targets and key signaling pathways of depression and ED were predicted through bioinformatics analysis, and a depression rat model was established by inducing chronic restraint stress. Pathological changes in rat penis tissue were studied by hematoxylin and eosin staining. The serum dopamine level was quantified by an enzyme-linked immunosorbent assay. The expression of related proteins and mRNA was detected by western blotting and real-time quantitative reverse transcription-polymerase chain reaction.

Results: Hematoxylin and eosin staining showed pathological damage in the penile tissue of the model group rats. The serum dopamine level, dopamine receptor D2 (DRD2) and solute carrier family 6 member 3 (SLC6A3) protein levels in penile tissue, and DRD2 and SLC6A3 mRNA levels were lower in the model group than in the control group.

Conclusion: The decrease in erectile function in the depression rat model was related to dysfunction of the dopamine system and dopaminergic synapse signaling pathway.

Keywords: Depression; dopamine; dopamine receptor D2; dopaminergic synapse signaling pathway; erectile dysfunction; solute carrier family 6 member 3.

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Conflict of interest statement

Declaration of conflicting interest: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Bioinformatics analysis. (a) Intersection of targets in depression and erectile dysfunction. (b) Depression–erectile dysfunction–targets network built by Cytoscape. (c) PPI network built by Cytoscape and (d) PPI network processed by the Cytoscape plug-in CytoHubba. PPI, protein–protein interaction.
Figure 2.
Figure 2.
Analyses of pathway enrichment using GO and KEGG databases. The Y-axis is the name. The X-axis is the richness factor. The size of the node is proportional to the number of genes. The node color is proportional to the P value. GO, Gene Ontology; KEG, Kyoto Encyclopedia of Genes and Genomes; BP, biological process; CC, cellular component; MF, molecular function.
Figure 3.
Figure 3.
Sucrose water preference test and open field test before and after modeling. (a) Sucrose water preference index of rats in the C and M groups. (b) The horizontal movement scores of rats in the two groups and (c) The vertical movement scores of rats in the two groups. Values are the mean ± standard error of the mean (n = 10 animals per group). The t-test was used. Group M was compared with group C, * represents P < 0.05. C, control; M, model.
Figure 4.
Figure 4.
Dopamine serum level and histological analysis of penile tissues. (a) The serum level of dopamine in rats in the C and M groups. Values are the mean ± standard error of the mean (n = 10 animals per group). The t-test was used. Group M was compared with group C, * represents P < 0.05. (b) Scatter plot of the serum level of dopamine in rats in the two groups and (c) Analyses of penile tissue in rats using HE staining at the indicated magnifications. The penile tissue of rats was stained with HE to observe pathologic changes in the penis under an optical microscope. C, control; M, model; HE, hematoxylin and eosin.
Figure 5.
Figure 5.
Analysis of the dopaminergic synapse signaling pathway. (a) Western blotting showing the expression of DRD2, SLC6A3, and COMT proteins. GADPH was used as a loading control. (b), (c), and (d) The light blue bars represent the expression of DRD2, SLC6A3, and COMT in group C. The dark blue bars represent the expression of DRD2, SLC6A3, and COMT in group M. (e) and (f) mRNA expression of DRD2 and SLC6A3 in rat penile samples. Values are the mean ± standard error of the mean (n = 10 animals per group). The t-test was used. Group M was compared with group C, * represents P < 0.05. DRD2, dopamine receptor D2; SLC6A3, solute carrier family 6 member 3; COMT, catechol-O-methyltransferase; GAPDH, glycerol 3-phosphate dehydrogenase; C, control; M, model; OD, optical density.
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