RESUMEN
PURPOSE: To evaluate the expression of core molecular clock genes/proteins in penile cavernous tissue from healthy male subjects and to determine whether their expression has circadian variation. MATERIALS AND METHODS: Corpus cavernosum biopsy samples were obtained from 10 healthy males with penile deviation or fracture who underwent surgical intervention during the day and night. The daytime group (n=5) underwent corpus cavernosum tissue sampling during zeitgeber time (ZT) 8-12, while the nighttime group (n=5) underwent sampling during ZT 20-24. The expression and localization of BMAL1, CLOCK, PER1, PER2, PER3, CRY1, and CRY2 proteins were analyzed using immunohistochemistry and quantified using H-score analysis. RT-qPCR analysis was performed to assess the expression of core molecular clock genes in the corpus cavernosum tissue of 5 additional daytime patients. RESULTS: The expression of core molecular clock proteins was detected in vascular endothelial cells (VECs) and smooth muscle cells (SMCs) in corpus cavernosum during daytime and nighttime. BMAL1 exhibited the most significant nuclear expression during daytime in both cell types, whereas its expression decreased significantly at night. In VECs, a significant decrease in the nuclear expression of CRY1 was observed at night. In SMCs, a significant decrease in the cytoplasmic expression of PER3 was observed at night. The expression patterns of the core molecular clock genes were ascertained through a RT-qPCR analysis. CONCLUSIONS: Our research provides compelling evidence that core molecular clock genes are distinctly expressed in penile tissue in humans. Furthermore, we observed the expression of molecular clock proteins within the VECs and SMCs of the corpus cavernosum, with BMAL1 being the most prominently expressed. The discovery of core molecular clock genes in penile tissue, as well as proteins within the SMCs and VECs of the corpus cavernosum, introduces the potential significance of the molecular clock mechanism in the physiology of penile erection.
RESUMEN
PURPOSE: This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. METHODS: CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 µg/100 µl; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. RESULTS: Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. CONCLUSION: In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.
