Assessment of novel drugs for treating preterm labour using a translational model

UoM administered thesis: Phd

  • Authors:
  • Ammar Mohammed

Abstract

The uterus and placenta are essential organs playing key roles in reproductive processes. Labour is modulated by several factors such as sex hormones, nitric oxide, prostaglandins and the ROCK pathway, which stimulate the uterus via the phosphorylation of myosin-light chain (MLC). Abnormal function of these factors may lead to preterm labour (PTL) which still has no effective management strategies. The aims of this project were to: (i) examine the regulation of myometrial contractility in non-pregnant and pregnant mice, (ii) assess the ability of ripasudil (a ROCK inhibitor) to diminish uterine contractions, (iii) evaluate the effect of NO on myometrial contractility, and (iv) investigate the influence of administrating empty and NO-loaded liposomes on the level of lipid mediators in the uterus and placenta from C57 and eNOS KO pregnant mice at term. Results showed a significant higher contractility of the upper segment of uterus as compared to the lower segment (p4×108) compared with the Free SE175. SE175 significantly increased the concetration of the 15 HETrE. The majority of lipid mediators detected were the LOX-derived (myometrium) and COX-derived (placenta). In conclusion, the data support the higher myogenic activity of uterus in pregnant mice. It demonstrated for the first time that ppMLC is expressed in mouse myometrium and that ROCK inhibition is a promising tocolytic candidate for the treatment of PTL. Targeted liposomes were effective in modulating the level of certain lipid mediators. Administration of NO-donors at late pregnancy can regulate uterine activity and control placental blood flow.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date1 Aug 2020