A circadian rhythm is an internalized timing system that synchronizes the cellular, behavioral, and physiological processes of organisms to the Earth’s rotation. Because all physiological activities occur at a specific time, circadian rhythm disturbances can lead to various pathological disorders and diseases. Growing evidence has shown that the circadian clock is tightly connected to male fertility, and circadian perturbations contribute to infertility. The night shiftwork, insufficient sleep, and poor sleep quality are common causes of circadian disturbances, and many studies have reported that they impair sperm quality and increase the risk of male infertility. However, research on the impacts of light, body temperature, and circadian/circannual rhythms is relatively lacking, although some correlations have been demonstrated. Moreover, as the index of sperm quality was diverse and study designs were non-uniform, the conclusions were temporarily inconsistent and underlying mechanisms remain unclear. A better understanding of whether and how circadian disturbances regulate male fertility will be meaningful, as more scientific work schedules and rational lifestyles might help improve infertility.

The circadian rhythm is an internal timing system, which is generated by circadian clock genes. Because the circadian rhythm regulates numerous cellular, behavioral, and physiological processes, organisms have evolved with intrinsic biological rhythms to adapt the daily environmental changes. A variety of pathological events occur at specific times, while disturbed rhythms can lead to metabolic syndrome, vascular dysfunction, inflammatory disorders, and cancer. Therefore, the circadian clock is considered closely related to various diseases. Recently, accumulated data have shown that the penis is regulated by the circadian clock, while erectile function is impaired by an altered sleep-wake cycle. The circadian rhythm appears to be a novel therapeutic target for preventing and managing erectile dysfunction (ED), although research is still progressing. In this review, we briefly summarize the superficial interactions between the circadian clock and erectile function, while focusing on how disturbed rhythms contribute to risk factors of ED. These risk factors include NO/cGMP pathway, atherosclerosis, diabetes mellitus, lipid abnormalities, testosterone deficiency, as well as dysfunction of endothelial and smooth muscle cells. On the basis of recent findings, we discuss the potential role of the circadian clock for future therapeutic strategies on ED, although further relevant research needs to be performed.

Background Aspirin is the most widely used medicine since its synthesis, we aim to investigate the controversial relationship between aspirin and erectile function.Methods Thirty-six healthy young rats were grouped and administrated with small (10 mg/kg/d) and big (150 mg/kg/d) dose aspirin for 1 and 3 months, respectively; eighteen rats with bilateral cavernous nerve crush (BCNC) process were gavaged with small dose aspirin for 1 month. The 6-keto PGF1a, PGE2, and TXB2 in corpus cavernosum were detected to verify the bioactivity of aspirin. The mICP, mICP/MAP ratio, and concentrations of total NO, cAMP, as well as cGMP were selected to determine the erectile function.Results For the healthy young rats, aspirin significantly decreased the 6-keto PGF1a and PGE2 levels than control group, however, mICP, mICP/ MAP, total NO, cAMP, and cGMP levels was similar, whether with bigger dosage or longer duration. In BCNC groups, aspirin also significantly inhibited prostaglandin productions, however, it did not improve the impaired erectile function as well.Conclusion Long-term aspirin (even with higher dosage or longer duration) administration did not strength nor deteriorate erectile function for healthy young rats, while it did not improve the BCNC-induced erectile dysfunction as well.

Penile size is closely concerned and short penis contributes serious sexual dysfunction and tremendous psychological problems to couples. Androgen is essential for penile development and testosterone replacement is recommended to patients with micropenis. We previously proved that inhibiting activity of lysyl oxidase (Anti-lysyl oxidase, Anti-LOX) combined with vacuum erectile device (VED) lengthened penis by remodeling tunica albuginea. We thus explored whether androgen supplement could accelerate tunica albuginea remodeling (induced by Anti-LOX + VED) to promote penile growth. Forty-two SD male rats (4 weeks old) were purchased and divided into 7 groups: control, Anti-LOX, HCG, VED (with a negative aspirated pressure of -300 mmHg), Anti-LOX + VED, HCG + VED, and Anti-LOX + HCG + VED. After an intervention for 4 weeks, all rats’ penile length, exposed penile length, and erectile function were measured. Serum samples were collected to detect hormone levels and penile corpus cavernosum were harvested for histo-pathological analysis. All intervention groups showed significantly longer penis than controlled rats. Anti-LOX sharply increased penile length and exposed length by 15% and 9% respectively, this lengthening effect was more obvious in Anti-LOX + VED group (26% and 19%, respectively). Although HCG promoted penile length by 8%, this effect was slight for exposed length (3%). Moreover, Anti-LOX + HCG + VED dramatically increased penile length and exposed length by 22% and 18%, respectively, which was similar with that in Anti-LOX + VED (26% and 19%, respectively). HCG dramatically stimulated testosterone and dihydrotestosterone secretions than control group, whether with or without Anti-LOX and VED; while it induced more AR expression than other groups. Finally, all procedures did not improve or deteriorate normal erectile function. Although we verified that Anti-LOX + VED lengthened penis by inducing tunica albuginea remodeling, however, androgen supplement did not synergize with Anti-LOX + VED to accelerate albuginea remodeling to facilitate penile growth.

Penile size is closely concerned and short penis contributes serious sexual dysfunction and tremendous psychological problems to couples. Androgen is essential for penile development and testosterone replacement is recommended to patients with micropenis. We previously proved that inhibiting activity of lysyl oxidase (Anti-lysyl oxidase, Anti-LOX) combined with vacuum erectile device (VED) lengthened penis by remodeling tunica albuginea. We thus explored whether androgen supplement could accelerate tunica albuginea remodeling (induced by Anti-LOX+VED) to promote penile growth. Forty-two SD male rats (4 weeks old) were purchased and divided into 7 groups: control, Anti-LOX, HCG, VED (with a negative aspirated pressure of -300 mmHg), Anti-LOX+VED, HCG+VED, and Anti-LOX+HCG+VED. After an intervention for 4 weeks, all rats’ penile length, exposed penile length, and erectile function were measured. Serum samples were collected to detect hormone levels and penile corpus cavernosum were harvested for histo-pathological analysis. All intervention groups showed significantly longer penis than controlled rats. Anti-LOX sharply increased penile length and exposed length by 15% and 9% respectively, this lengthening effect was more obvious in Anti-LOX+VED group (26% and 19%, respectively). Although HCG promoted penile length by 8%, this effect was slight for exposed length (3%). Moreover, Anti-LOX+HCG+VED dramatically increased penile length and exposed length by 22% and 18%, respectively, which was similar with that in Anti-LOX+VED (26% and 19%, respectively). HCG dramatically stimulated testosterone and dihydrotestosterone secretions than control group, whether with or without Anti-LOX and VED; while it induced more AR expression than other groups. Finally, all procedures did not improve or deteriorate normal erectile function. Although we verified that Anti-LOX+VED lengthened penis by inducing tunica albuginea remodeling, however, androgen supplement did not synergize with Anti-LOX+VED to accelerate albuginea remodeling to facilitate penile growth.