Fibroblasts in the penis are more important for erectile function than previously thought - frequent erections are important for maintaining erectile function.

New research from my home country of Sweden and our most prestigious medical science institution, Karolinska. I explain and draw an important conclusion at the very end. 

Regular erections could be important for maintaining erectile function, according to a new study on mice published in Science by researchers at Karolinska Institutet. “We discovered that an increased frequency of erections leads to more fibroblasts that enable erection and vice versa, that a decreased frequency results in fewer of these cells,” says principal investigator Christian Göritz.

Go read about the study:

Corpora cavernosa fibroblasts mediate penile erection

https://www.science.org/doi/10.1126/science.ade8064

 

The corpora cavernosa are masses of vascular tissue that can fill with blood and thereby enlarge upon stimulation, creating the structure needed for penile erection. By studying the underlying mechanism for this process in mice, Guimaraes et al. determined that perivascular fibroblasts in the corpora cavernosa play a key role in erection physiology (see the Perspective by Ryu and Koh). Norepinephrine is a vasoconstrictor that restricts penile blood flow at baseline, whereas vasodilators released by sexual arousal counteract its effects, allowing an erection to take place. Recurrent erectile activity down-regulates Notch signaling, thereby increasing the numbers of perivascular fibroblasts, and these fibroblasts then suppress vasoconstrictive norepinephrine signaling. Conversely, aging is associated with a decrease in these fibroblasts, contributing to the risk of erectile dysfunction. —Yevgeniya Nusinovich

Penile erection, a physiological process crucial for sexual function, relies on the intricate regulation of blood flow within the sponge-like vascular bed of the corpora cavernosa (CC). In the flaccid penis, sympathetic release of the vasoconstrictor norepinephrine maintains vascular smooth muscle cells tonically contracted, restricting penile blood flow. Upon sexual arousal, nitric oxide and acetylcholine are released from parasympathetic nerves, mediating vasodilation through the relaxation of vascular smooth muscle cells. The incoming blood fills the CC, leading to penile erection. Despite the recognized importance of endothelial and vascular smooth muscle cells in the erectile process, the vast population of fibroblasts in the CC has been largely overlooked.

Fibroblasts constitute the largest cell population in the human CC, but their physiological functions remain largely unexplored. Our aim was to elucidate the contribution of CC fibroblasts to the regulation of penile blood flow. Characterization of CC fibroblasts through single-cell gene expression profiling and histological analysis in cleared tissue revealed their heterogeneity and integration in the erectile tissue. Using genetic targeting and optogenetic-induced fibroblast depolarization, we found that fibroblasts actively participate in the regulation of penile blood flow. Furthermore, by chronically altering erection frequency using chemogenetic modulation of brain regions responsible for arousal, we addressed the impact of erection recurrency on fibroblast number and blood flow regulation. Finally, we investigated whether the number of fibroblasts is altered by aging and how a reduction in fibroblast number affects penile blood flow.

Our study revealed that fibroblasts in the CC play a pivotal role in supporting vasodilation by modulating norepinephrine availability. The efficacy of this process depends on the number of fibroblasts, which is regulated by erectile activity. Penile erection temporarily alters the spatial arrangement of cells throughout the CC, leading to down-regulation of Notch signaling in fibroblasts. Inhibition of Notch signaling in fibroblasts leads to a substantial increase in fibroblast numbers, which can cause long-lasting erections characteristic of priapism. Constitutively active Notch signaling decreases fibroblast numbers and lowers penile blood perfusion. Boosting the frequency of erections reduces Notch signaling, increasing fibroblast numbers and promoting vasodilation. Conversely, a reduction in erection recurrency increases Notch signaling, decreasing the number of fibroblasts and diminishing penile blood perfusion. Aging, one of the major risk factors for erectile dysfunction, reduces the number of penile fibroblasts and limits penile blood perfusion. A reduction of penile fibroblasts in young animals mimics the penile blood flow phenotype of aged animals.

Fibroblasts, previously regarded as static and homogeneous cells, are emerging as a dynamic and heterogeneous cell population. We discovered that CC fibroblasts act as key blood flow regulators, shifting the balance between vasodilators and the vasoconstrictor norepinephrine toward vasodilation. Notch signaling serves as a central hub coordinating fibroblast turnover, norepinephrine sensitivity, and, ultimately, the erectile process. The dynamic regulation of fibroblast numbers coupled to erection recurrency underscores the plasticity of erectile function. This positive feedback loop may exacerbate erectile dysfunction in chronic conditions such as aging or diabetes. Indeed, our observations in aged animals suggest a potential link between reduced fibroblast number and erectile dysfunction, highlighting the clinical relevance of understanding the cellular mechanisms of erection. Overall, this study provides a mechanism for modulation of penile erection and establishes a foundation for further research in the field of sexual health.

 

Pop sci news article about the study, in somewhat more accessible language

https://news.ki.se/fibroblasts-in-the-penis-are-more-important-for-erectile-function-than-previously-thought

 

To me this explains a lot about why PE has so massively improved my erection quality. Fibroblast proliferation is triggered by the stretching forces we cause, and also by the hypoxic conditions we accomplish with ischemic clamping.

 

It also tells me how edging and relatively frequent masturbation is golden for PE, since it aids fibroblast proliferation.

 

This finally answers the question whether no-fap is beneficial for PE: It isn't!