Duygu MUTLUAY, Özlem ÖZBEY, Leyla KILINÇ, Jale ÖNER, Hakan ÖNER, İsmail ÜSTÜNEL

İmplantasyon ve desidualizasyon esnasında fare uterus dokusunda PROK1 ve PROKR1’in ekspresyonu

İmplantasyon, embriyonun özel hücreleri olan trofoektoderm ve trophoblast vasıtasıyla uterus dokusuyla bağlantı kurulması ile son bulan bir süreçtir. Başarılı bir implantasyon, plasentasyon ve sonrasında gebeliğin gerçekleşebişmesi için damardan zengin bir endometriyum, koordine olmuş bir damar gelişimi ve plasental villöz damarların genişlemesine gereksinim vardır. Bu bilgiler anjiyogenezin gebeliğin erken dönemleri için önemli fizyolojik bir süreç olduğunu göstermiştir. Prokinetisin ailesinin bir üyesi olan vasküler endoteliyal büyüme faktörü (EG-VEGF) diğer bir adıyla prokinetisin 1 (PROK1) plasentayı da içine alan spesifik endokrin dokular için anjiyogenik bir faktör olarak rapor edilmiştir. Biyolojik aktivitesini iki G protein bağlı reseptör, prokinetisin reseptör 1 (PROKR1) ve prokinetisin reseptör 2 (PROKR2) aracılığı ile gerçekleştirir. Trofoblast invazyonunu kontrol eden PROK1ve PROKR1 plasentada eksprese edilmektedir. Ayrıca, PROK1 plasental anjiyogenezi kontrol eder ve yüksek oranda birinci trimester boyunca eksprese edilmektedir. Çalışmamızda kullanılan dişi fareler, östrus siklusu tayini yapıldıktan sonra, 1 gece erkek fareler ile birlikte bırakılarak gebe kalmaları sağlandı. Vaginal plak (tıkaç) görülen dişiler gebe olarak değerlendirildi. Gebeliğin 1, 2, 3, 4, 5, 6, 7 ve 8. günlerinde alınan uterus doku örneklerinde Western Blot yöntemi kullanılarak PROK1, PROKR1 proteinlerinin ekspresyon analizi yapıldı ve günler arasında bir farklılığın olup olmadığını belirlemek için varyans analizi yöntemi kullanıldı. Çalışmamızda PROK1 ve PROKR1 proteinlerinin gebeliğin ilk 8 günü boyunca eksprese edildiği görüldü. Bu bulgular bize PROK1 ve PROKR1 proteinlerinin erken embriyo gelişimi ve implantasyon sırasında eksprese edildiğini ve bu proteinlerin embriyo gelişiminde önemli roller oynuyor olabileceğini önermiştir.

Anahtar Kelimeler:

Desidualizasyon, İmplantasyon, Preimplantasyon, Prokinetisin 1, Prokinetisin reseptör 1

Expression of PROK-1 and PROKR-1 in mouse uterine tissue during implantation and decidualization

Implantation is a process culminating whereby specialized cells of the embryo, the trophectoderm and trophoblast, establish contact with a specialized tissue of the mother, the uterus. During this process trophoblast invades the maternal endometrium and makes contact with the maternal blood supply, which is critical for establishment of pregnancy. Successful implantation, placentation and subsequent gestation require coordinated vascular development to provide a richly vascularized endometrium for implantation and the development and expansion of the placental villous vasculature to facilitate transport of nutrients and oxygen to the embryo. This knowledge supports that angiogenesis is an essential physiological component of implantation, and placental and embryonic development in early stages of pregnancy. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1(PROK1), is the member of the prokineticin family which is an angiogenic factor reported to be specific for endocrine tissues, including the placenta. Its biological activity is mediated via two G protein coupled receptors, prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). PROK1 and PROKR1 are expressed in placenta and control trophoblast invasion. Additionally, PROKR1 controls placental angiogenesis and is highly expressed throughout the first trimester. Mice were mated overnight after determining of estrus. Pregnant mice were determined by vaginal plug control. Expressions of PROK-1 and PROKR1 proteins were determined by Western Blot analysis in uterine tissue samples taken at 1, 2, 3, 4, 5, 6, 7, and 8 days of gestation and the results were compared statistically by using the variance analysis to determine whether there was a significant difference between days. In our study, we showed that PROK1 and PROKR1 proteins were expressed during the first 8 days of gestation. These findings suggested that PROK1 and PROKR1 proteins were expressed during early embryo development and implantation and these proteins may play important roles in embryo development.

Keywords:

Desidualization, Implantation, Preimplantation, Prokineticin, Prokineticin receptor 1,

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