Potential Contribution of Early-Life Obesity to Cavernosal and Pudendal Dysfunction in Young Adults Rats

Introduction/Objectives: – Obesity is recognized as a risk factor for erectile dysfunction (ED), yet it remains unclear whether childhood obesity contributes to the onset of ED in young adulthood. We hypothesize that early-life obesity leads to cell senescence, hence compromises cavernosal and pudendal function. Methods: – We compared the cavernosal and pudendal function of young adult male Wistar rats (5-month-old) from early-life obesity model to controls. At postnatal day (PND) 1, rats were assigned into small litter (SL, 2 male + 1 female pup/dam) or normal litter (NL, 5 male + 5 female pups/dam), with the SL inducing overfeeding during lactation. At PND 21, both groups were weaned, housed in equal-sized colonies (3 rats/cage), and fed standard chow to the end of the study. At PND 121, we confirmed the early-life obesity model from increased body mass of SL rats. The study concluded on PND 160, when the body mass, fat pad deposition, and mean arterial pressure (MAP) by tail-cuff were evaluated. Molecular studies and functional reactivity were conducted on the corpus cavernosum (CC) and pudendal artery (PA) samples collected from both groups. Concentration-response curves to phenylephrine (PE) and acetylcholine (ACh) were assessed. In the CC, contraction and relaxation to electrical field stimulation (EFS) were recorded. RNA sequencing (RNA-seq) and downstream analysis were conducted for differentially expressed genes (DEGs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to assess the expression levels of Bgn (biglycan), Col1a2 (collagen type I alpha 2), P53 (tumor protein P53), and Glb1 (galactosidase beta 1). Non-linear regression analysis was used for concentration-response curves, and data were analyzed via Student’s t-test, expressed as mean ± S.E.M., with statistical significance set at p<0.05. Results: – At PND 160, body mass showed no significant difference between SL group (594±14g) and NL group (559±13g). However, higher fat deposition was shown in SL rats (retroperitoneal fat: SL 11.25±1.23g vs NL 7.47±0.69g; perigonadal fat: SL 13.24±1.16g vs NL 10.05±0.55g). MAP was also elevated in SL group (120.5±1.20 mmHg) in comparison with NL group (114.9±0.58 mmHg). In the PA, ACh-induced relaxation was reduced in SL (Emax: SL 28±6% vs NL 68±5.5%), while PE-induced contraction remained unchanged. In the CC, EFS-induced relaxation was significantly lower in SL rats (16 Hz: SL 2.39 ± 0.53% vs NL 3.06 ± 0.28%). Both EFS- and PE- induced contractions were increased in SL group which was prevented by indomethacin. The RNA-seq analysis identified 135 downregulated and 158 upregulated genes in the PA, and 54 downregulated and 70 upregulated genes in the CC. And the RT-qPCR test revealed increased expression level of Bgn, Col1a2, P53, and Glb1 in the CC of SL rats. Conclusions: – Our findings suggest that early-life obesity is associated with long-term cavernosal and pudendal impairments, which may contribute to ED in young adulthood. These effects appear to involve mechanisms related to fibrosis and cell senescence. Further studies are needed to establish a direct causal link between early-life obesity and these vascular and functional alterations. NIDDK 132948 and NHLBI 149762 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.