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العنوان
Effect of dynein mRNA expression and autophagy on fertility potential of human spermatozoa /
المؤلف
El-Zeiny, Dina Ashraf Ahmed.
هيئة الاعداد
باحث / دينا أشرف أحمد الزيني
مشرف / عادل عبد القادر زلطة
مشرف / كريمة محمد السبخاوي
مشرف / ريهان منير يوسف يوسف سليمان
مشرف / محمد خالد جلال سليم.
الموضوع
Infertility. Spermatozoa. Genetics. DNA Damage. Epigenesis, Genetic.
تاريخ النشر
2020.
عدد الصفحات
237 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
1/10/2020
مكان الإجازة
جامعة المنصورة - كلية الطب - لكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

from 279

from 279

Abstract

Infertility is a significant reproductive problem influencing about 15% of couples. Males are responsible for about half of these cases. Autophagy affects activation of sperm flagellar motility, acrosome reaction or capacitation. In contrast, it can trigger apoptosis that may lead to oligozoospermia and infertility. Dyneins, the microtubule‐dependent ATPases, are the molecular motors responsible for sperm motility. DYNLT1 protein is situated to Golgi complexes, and was found in sperm tails and oocytes. It plays a role in vesicle transport, lymphocyte division, and human embryo implantation. Autophagy is controlled by several proteins such as Beclin1 which activates autophagosome formation and fusion with lysosome.The aim of this study was to assess DYNLT1 mRNA expression in mature spermatozoa and investigate its association with Beclin1 expression as a marker of autophagy which may help in understanding the pathogenesis in different groups of male infertility.It included 80 males attending the Andrology Outpatient Clinic, Mansoura University Hospital. The studied subjects were grouped into: Healthy fertile control group (n=20), Varicocele infertile patients (n=20), Male accessory gland infection (MAGI) infertile patients (n=20), Idiopathic infertile patients (n=20). Fresh semen samples were collected from cases by masturbation after 3-4 days of sexual abstinence and allowed to liquefy for 15-30 minutes. After complete liquefaction, computer assisted semen analysis using Autosperm and acrosin activity test were performed according to the recommendations of the world health organization. Sperm morphology was evaluated by phase contrast microscope and Sperm Mac stain. WBCs were determined by peroxidase stain.Moreover, the results of this study revealed a significant increase of DYNLT1 mRNA expression in mature spermatozoa extracted from all studied subjects compared with the whole sample. However, Beclin1 mRNA and protein expression were significantly decreased in extracted mature spermatozoa versus whole semen samples from different groups.Multiple stepwise regression analysis was done to determine the independent variables which could explain the changes of Beclin1 mRNA, protein and DYNLT1 mRNA expression in whole sperm pellet. The most significant variables that affect Beclin1 mRNA expression were velocity, normal morphology, and MDA per 108 sperm. However, grade (A+B) motility, MDA/108 sperm and WBCs were the independent variables which could explain the changes of Beclin1/108 sperm. Furthermore, the most significant variables which could explain DYNLT1 mRNA expression variations were normal morphology, MDA per 108 sperm and acrosin activity index.Conclusion: The decreased expression of DYNLT1 mRNA and the marked expression of Beclin1 mRNA and protein in the spermatozoa of infertile males from different etiologies suggest that these markers might have a role in spermatogenesis and fertility potential of sperm. According to the present study, autophagy process could be also involved in the regulation of additional functions in human spermatozoa, such as acrosome reaction or maturation.The positive correlation between both Beclin1 mRNA and protein expression, and MDA per sperm revealed the combined relationship between oxidative stress and autophagy that might be of many practical and therapeutic applications.