الفهرس 
EndometriosisOnly 14 pages are availabe for public view
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Abstract
Endometriosis is a chronic gynecological disease characterized by the growth of ectopic endometrial tissue outside the uterine cavity, ovaries, fallopian tubes, intestine and even on the bladder. It affects about 10% of women and the main symptoms are dysmenorrhea and subfertility.
The most accepted theory is that of retrograde menstruation, according to it menstrual endometrial fragments migrate through the fallopian tubes to the peritoneal cavity, where they implant, proliferate and invade the pelvic peritoneum.
The etiology of endometriosis is highly complex and although it is a benign disease. It has several biological behaviors similar to malignant lesions including cell invasion, neo-angiogenesis and decreased apoptosis. Because laparoscopy is regarded as the gold standard for confirming the diagnosis, the prevalence of endometriosis is underestimated. The condition affects about 10-15% of all women of reproductive age globally.
Mitochondrion is majorly involved in energy production via the electron-transport chain, oxidative phosphorylation system (OXPHOS) and required for normal cellular physiology. Mitochondrial DNA copy number (mtDNA CN) is a promising biomarker of mitochondrial function and altered levels are associated with the development of chronic diseases and cancer. The regulation of mtDNA CN is complex and depends on several factors, including mtDNA mutations and genetic variations within the genes involved in mtDNA replication and transcription.
Mitochondrial transcription factor A (TFAM) plays a key role in replication and transcription of mtDNA. It is also important for the maintenance of mtDNA integrity and stability, thus mirrors the changing levels of mtDNA in the cell. TFAM has shown to play a central role in the
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maintenance and regulation of mtDNA CN, inflammatory response and mitochondrial genome activity.
Endometriosis is a benign but invasive gynecological disease with increased levels of reactive oxygen species (ROS) and oxidative stress. Mitochondria as a major source of ROS generation may be implicated in the pathogenesis of endometriosis. Studies showed an association of TFAM polymorphism with the progression of inflammatory diseases like Alzheimer’s disease and Huntington’s neuropathy, diabetic neuropathy and ovarian cancer.
The aim of the study is to analyze the potential link between mtDNA CN and risk of endometriosis &its association with TFAM gene polymorphism in Egypt. This case control study was done by cooperation between Medical Biochemistry & Molecular Biology and Obstetrics & Gynecology departments, Faculty of Medicine, Menoufia University during the period from January till August 2022. A total of one hundred sixty women undergoing laparoscopy for suspected endometriosis are included in the study. According to result of laparoscopy, subjects were classified into two groups endometriosis group (group I) and controls (group II).
Endometriosis group included 80 females confirmed by laparoscopy and histopathology. Their mean age ±SD was 29.7±5.17 (range: 21–42) years. The control group included 80 age matched women with no evidence of endometriosis on laparoscopy. Their mean age ±SD was 31.24±5.17 (range: 21–42). All the participants have been subjected to the following: Full history taking, general examination, local pelvic examination, abdomino-pelvic ultrasound and laboratory investigation including: Complete blood
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count, serum CA125, Hormonal assay of female sex hormones: follicle-stimulating hormone, luteinizing hormone, progesterone, estradiol and prolactin. Quantification of mitochondrial DNA copy number by real time Polymerase Chain Reaction and Genotyping of TFAM single nucleotide polymorphism (rs 1937) by real time PCR using TaqMan allelic discrimination assay technique. The obtained data were tabulated and subjected to statistical analysis using different tests of significance and the results of the present study can be summarized as follows:
There was highly significant statistical difference between group I and group II regarding family history and menarche, while there was no significant statistical difference between them regarding age, body mass index (BMI), parity and menstrual pattern.
50% of endometriosis cases were ovarian lesions, 86.3% presenting with pain and most of patients are in stage III (38.8%) and stage VI (36.3%).
There was highly significant statistical increase of FSH, estradiol, progesterone, prolactin, CA125 levels in group I when compared to group II. While there was no significant statistical difference between the two groups regarding Hb and LH levels.
There was highly significant statistical decrease in mtDNA CN in group I when compared to group II.
There was significant statistical association between mtDNA CN and family history.
At cut off point ≤ 21 for the mtDNA CN, mtDNA CN alone has higher sensitivity, specificity, positive and negative predictive values than CA125 alone at cutoff point >27.3 for CA125.
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Combined mtDNA CN and CA125 have higher sensitivity, specificity, positive and negative predictive values than each alone.
Genotype frequency & allelic distribution of TFAM SNP (rs 1937) was in Hardy-Weinberg equilibrium (HWE). The frequency of GC genotype was higher in group I when compared to group II (15% vs. 3.8%). There was also a higher C allele frequency in group I compared to group II (7.5% vs. 1.9%). The presence of GC genotype and C allele increased the risk for developing endometriosis.
There was significant statistical association between GC genotype and ovarian site and stage IV. There was no significant statistical association between different genotypes and age, BMI, menarche, family history, parity, menstrual pattern and presence of pain.
There was no significant statistical association between TFAM (rs1937) genotypes and different laboratory parameters.
Family history was the most significantly associated parameter with the risk of endometriosis by univariate analysis followed by TFAM (rs 1937) genotype GC, then by CA125 then mtDNA CN and menarche. While the multivariate analysis showed that endometriosis was associated with elevated CA125 levels followed by lower mtDNA CN.