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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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Implantation is essential for a successful pregnancy. Despite the increasing number of studies, implantation is still an unknown process. This study aimed to determine whether sirtuin-1 has a role in embryo implantation in oxidative stress-induced mice., Methods: Pregnant mice were separated into 5 groups: control, vehicle, paraquat, SRT1720, and SRT1720+Paraquat. Paraquat is a herbicide and is used to induce oxidative stress. SRT1720 is a specific sirtuin-1 activator. Implantation and inter-implantation sites were removed in the morning of the 5th day of pregnancy after Chicago blue injection was performed. Sirtuin-1 and Forkhead box O1 (FoxO1) were detected by immunohistochemistry and Western blot while acetylated lysine was evaluated by Western blot analysis. Reactive oxygen and nitrogen species (ROS/RNS) and superoxide dismutase (SOD) activity were determined by fluorometric and spectrometric methods, respectively., Results: Although there was no embryo implantation in paraquat-treated mice, 5 out of 9 SRT1720+Paraquat-treated mice had implantation sites which were significantly higher compared to the paraquat-treated group. Sirtuin-1 and FoxO1 expressions were increased at implantation sites of SRT1720-treated mice. ROS/RNS levels were decreased, while deacetylated FoxO1 levels and SOD activity were increased in SRT1720-treated mice., Conclusion: Our findings suggest that sirtuin-1 may play a role in embryo implantation against oxidative stress through FoxO1-SOD signaling., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C-8C) and sham groups (5S-8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.

The complex and multifactorial mechanisms that initiate and sustain the early labor process in the human uterus and cervix are still not well defined. Cervical maturation or ripening is likely to play a key role in preparing for birth. Prostaglandins have many different functions, including the regulation of uterine contractility and structure during pregnancy. The prostaglandin E1 analogue misoprostol is frequently used as a uterotonic and cervical ripening agent. Notch is a transmembrane receptor family responsible for basic functions such as cell survival, cell-cell communication, and differentiation and decidualization in pregnancy. However, our understanding of the effect of Notch signaling on the cervical ripening process is limited. This study was conducted in 20 pregnant women aged at 12 to 20 weeks of gestation undergoing medical abortion for fetal or maternal indications. True-Cut needle biopsies were taken from the anterior cervix 4 hours after oral ingestion of 200-μg misoprostol or before the ingestion of misoprostol in the control group. Cervical expression of Notch receptors and ligands changed during the early phase of prostaglandin-induced preterm labor. Four hours after the administration of misoprostol, it was seen that N1 expression increased in muscle, while DLL1 and J2 expression increased in blood vessels, and N4 expression increased in macrophages. Knowing the mechanisms that initiate preterm birth is the most important step in planning the treatments and actions to prevent premature birth. As a signal that affects and perhaps directs preterm labor, Notch is prone to be an important actor in this process.