Aglepriston ile gebelikleri sonlandırılan köpeklerde uterus ve maternal plasentada morfolojik değişiklikler, matriks metalloproteinazı-2, -9, doku uyuşum kompleksi molekülü-I, II ve steroid hormon reseptörlerinin belirlenmesi
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Date
2007
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Sağlık Bilimleri Enstitüsü
Abstract
Morphological Changes and Uterine and Maternal Placental Expression of MatrixMetalloproteinases-2, -9, Major Histocompatibility Complex-I, -II and SteroidReceptors After Interruption of Canine Pregnancy By AglepristoneIn this study, morphological changes and uterine and maternal placental expression of matrixmetalloproteinases (MMP)-2, -9, major histocompatibility complex (MHC) molecules-I, -II,progesterone receptors (PR) and estrogen receptors (ER) was investigated after termination ofmid-term canine pregnancy by a progesterone receptor antagonist, aglepristone. Tissue samplesof placental and interplacental uterine horns and uterine body were compared between dogs ofinduced resorption/abortion (Induced resorption/abortion, IRA group, n=10), spontaneousresorption/abortion (SRA Group, n=5) and normal pregnancy (Control Group, n=7). In addition,effects of aglepristone were clinically monitored in two subgroups of IRA group based on thestage of pregnancy drug administrations were done (Group I, 25-35 days of pregnancy, n=5;Group II, 36-45 days of pregnancy, n=5).Aglepristone, administered by two s.c. injections 24h apart, successfully terminatedpregnancies in all treated bitches. No side effects were observed. Interval between the first druginjection and expulsion of first foetus and the time needed for expulsion of all foetuses in groups Iand II (86,3±3,81; 70,74±52,49 and 14,75±4,20; 10,18±8,63, respectively) were not statisticallydifferent (p>0,05). Serum estradiol (E2) and progesterone (P4) concentrations were measured byEIA and chemiluminescence methods, respectively. There were no significant changes in serumE2 concentrations while P4 concentrations declined during the time course of pregnancytermination. Despite the tendency of declining, serum P4 levels on the day of pregnancytermination were above the basal hormone levels.The effects of aglepristone on the uterine morphology was assessed by macroscopicevaluation and morphometry. No effects were observed. Expression and localization of MMP-2,-9, MHC-I, -II, PR and ER were determined immunohistochemically. MHC-I molecules werepresent in all somatic cells. MHC-II molecule positive cells were observed in myometrium, basaland superficial endometriyal gland regions, endometrial connective tissue and glandularchambers part of the maternal placenta. MHC-II positive cells were counted and compared withinabovementioned regions and between training groups. Higher numbers of MHC-II positive cellswere encountered in the endometria of SRA and IRA bitches compared to those of controlbitches. ER and PR were detected in myometrial smooth muscle cells, stromal and epithelial cellsof endometrium and glandular chambers epithelium. Immunostainig was compared betweenwithin cell groups and between training groups by using an innunohistochemical staining score.Lower endometrial stromal cell staining scores were found in SRA and IRA groups compared tothe control group. MMP-2 immunoreactivity was observed in endothelia and smooth muscle cellsof blood vessels and in myometrium. Blood vessels, myometrial smooth muscle cells endometrialglandular and superficial epithelia and epithelium of glandular chambers were positive for MMP-9 staining. Active amounts of myometrial and endometrial MMP-2 and -9 in placental andinterplasental parts of uterine horns were measured by gelatine zymography. The amounts ofactive gelatinases did not differ significantly neither between Groups I and II nor between IRAand SRA groups. In contrast, lesser amounts of placental part myometrial and endometrial MMP-2,-9 active forms and interplacental myometrial MMP-2 active forms were measured in thecontrol group, compared to the amounts measured in IRA and SRA groups. MMP-2, -9 and PRmRNA was investigated by Reverse Transcryptase-Polymerase Chain Reaction. The presence ofMMP-2 and-9 was approved by PCR analyses. No PR mRNA was found in tissue samplesobtained from bitches in IRA and SRA groups while all tissue samples investigated in the controlgroup contained PR mRNA.In conclusion, aglepristone can effectively and safely be used in termination of caninepregnancy. The use of aglepristone in different stages of pregnancy does not effect the clinicaloutcome. The increase in the number of endometrial MHC-II positive cells, changes inendometrial stromal PR and ER and the uterine MMP-2,-9 activity are involved in spontaneousand aglepristone induced resorption/abortion in bitches.
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Keywords
Aglepristone, Matriks metalloproteinaz, Doku uyuşum kompleksi, Steroidreseptörü, Dişi köpek, Aglepristone, Matrix metalloproteinase, Major histocompatibility complex, Steroidreceptor, Bitch