الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 97 |  |  |
| | | from | 97 | | |
Abstract
Meiotic maturation of the oocytes is a critical process for generating healthy euploid egg able to be fertilized by healthy viable haploid sperm. Cathepsin roles in reproduction has been recently one of the research focus. A lot of research was done on CTSB and how it can affect the oocytes and embryos development potential, However CTSL role in regulating oocytes maturation and developmental competence in mammals has never been studied before. This study showed for the first time to our knowledge, the important role of CTSL in completion of meiosis I and production of healthy and euploid eggs using the mouse oocyte in vitro maturation system as a model.In the first experiment we detected the CTSL protein expression in all stages of meiosis I in mouse meiotic maturation, suggesting a requirement of this protein during meiosis.Then, we inhibited CTSL activity during meiosis to evaluate the importance for maturation, interestingly, we found a significant decrease in the maturation rates. Not only the maturation rates, but also the timing of maturation was delayed after CTSL inhibition for the pool of the oocytes that were able to finish the meiosis I suggesting that CTSL activity is important for proper changes that happen during meiosis. To understand what is the reason for reducing maturation rates and kinetics, we stained the chromosomes and spindles after CTSL inhibition, and we found a significant increase in the chromosomal misalignment that might be attributed to reduction of the maturation rates by activating the SAC mechanism.At the end, we evaluated the quality of the produced eggs after CTSL inhibition by doing the chromosomal counting assay and evaluate the ploidy status. Interestingly, we found CTSL inhibition significantly increases the aneuploidy incidence, confirming that CTSL is an essential protein which is required for completion of meiosis I in mouse oocytes unlike other cathepsins which are associated with low-quality oocytes and embryos. This study shed the light on one essential protease for meiotic maturation and open the door for doing more research to investigate the underlying mechanisms for deep understanding of aneuploidy reasons and infertility in mammals including human infertility.