title: Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats.
abstract: We aimed to evaluate: (1) endometrial and ovarian tissue injury caused by the glucose toxicity in diabetic rat model and (2) the effect of GLP-1 analog (exenatide) on endometrial and ovarian diabetes induced injury with emphasizing the underlying mechanism. The study group composed of 24 female rats assigned randomly into 3 groups. Group 1 was the control group (n = 8) and received no treatment. Diabetes was induced by intraperitoneal injection of streptozocin for 16 rats which are further assigned randomly into 2 groups: 1 ml/kg intraperitoneal saline was given to Group-2 (diabetic non-treated control group, 8 rats) and 10 µg/kg/day of intraperitoneal exenatide was given to Group 3 (exenatide treated group, 8 rats) for four weeks. After four weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Diabetes caused endometrial and ovarian tissue injury in rats (p < 0.0001). Serum transforming growth factor beta (TGF-ß), malonylaldehyde (MDA), pentraxin-3 (PTX-3) levels were higher in diabetic rats (p < 0.0001), whereas antimullerian hormone (AMH) was lower (p < 0.001). Serum levels of these markers reflected that Diabetes induced injury in the reproductive tract occured via oxidative stress, fibrosis and severe inflammation. Diabetes diminished ovarian reserve. Exenatide treatment improved the histological degeneration and fibrosis in the endometrium and ovary with concomitant decrease in inflammatory and oxidative stress markers (p < 0.05). Exenatide also improved ovarian reserve (p < 0.05). Glucose toxicity occured severely in ovary and endometrium in DM. After exenatide treatment; ovarian and endometrial injury and fibrosis seems to decrease significantly. The effects of exenatide in rat models give hope to prevent the women with DM from premature ovarian failure and endometrial dysfunction.
authors.affiliation: Obstetrics and Gynecology Department, Perinatology Division, Celal Bayar University School of Medicine, Manisa , Turkey .
authors.forename: Burcu
authors.initials: B
authors.lastname: Artunc-Ulkumen
authors.forename: Halil Gursoy
authors.initials: HG
authors.lastname: Pala
authors.forename: Emel Ebru
authors.initials: EE
authors.lastname: Pala
authors.forename: Altug
authors.initials: A
authors.lastname: Yavasoglu
authors.forename: Gurkan
authors.initials: G
authors.lastname: Yigitturk
authors.forename: Oytun
authors.initials: O
authors.lastname: Erbas
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000077270:Exenatide; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000097:blood; D065851:Ovarian Reserve / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000683:Serum Amyloid P-Component / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D014688:Venoms / Q000494:pharmacology*; D000099153:Pentraxins
chemical_list: D054304:Anti-Mullerian Hormone; D002097:C-Reactive Protein; D000077270:Exenatide; D008315:Malondialdehyde; D010455:Peptides; D000683:Serum Amyloid P-Component; D016212:Transforming Growth Factor beta; D014688:Venoms; D000099153:Pentraxins
keywords: Anti mullerian hormone; diabetes mellitus; endometrial dysfunction; exenatide; glucagone like peptide-1 (GLP-1) analogue; ovarian injury; oxidative stress; pentraxine-3