Kontrollü Ovaryen Hiperstimulasyon Uterusta Apelin ve Apelin Reseptör Ekspresyonunu Arttırır

Abstract

Amaç: Bu çalışmada, klinikle sıklıkla kullanılan süperovülasyon uygulamasının Apelin (APLN) ve Apelin Reseptör (APJ) ekspresyonunuterusta ne şekilde etkilediği araştırılmıştır. Gereç ve Yöntemler: Bu çalışmada 6-8 haftalık on iki dişi Balb-C faresi kullanıldı. Gruplar şu şekilde oluşturuldu; herhangi bir uygulama yapılmayan çiftleşmemiş kontrol grubu (Knt), bir günlük gebe olan gebe kontrol grubu (GK) ve 5 IU/fare/intraperitoneal (ip) PMSG ve 5 IU/fare/ip hCG uygulanan ve gebe olan (P+H) grubu. P+H ve GK gruplarındaki farelerde, çiftleşmeye atıldıktan sonraki gün vajinal plak kontrolü yapılarak vajinal plak pozitif fareler gebeliğin 0.5. gününde kabul edildi. P+ H grubundaki fareler, hCG enjeksiyonundan 42 saat sonra sakrifiye edildi. Tüm gruplardan immünohistokimyasal analiz için uterus dokuları elde edilerek parafin kesitler elde edildi. Yağ dokusu pozitif kontrol olarak kullanıldı. Bulgular: İmmunohistokimyasal boyanma yoğunluğu değerlendirildiğinde; APLN, Knt grubunda özellikle uterus bezlerinde ve bez etrafındaki stromal hücrelerde görüldü. APJ’nin uterustaki lokalizasyonu da APLN’ye benzerdi. GK grubunda APLN ve APJ ekspresyon seviyeleri kontrol grubu ile benzerdi. Ancak APJ’nin lokalizasyonu değerlendirildiğinde, Knt grubundan farklı olarak özellikle uterusun perimetriyal bezlerinde yoğun olarak ekspre edildiği izlendi. APLN ekspresyonu, Knt ve GK grupları ile karşılaştırıldığında P+H grubundaki endometrial bezlerde ve stromada belirgin olarak artmıştı (p<0.05). Sonuçlar: PMSG ve hCG uygulaması sonrasında uterusta APLN ve APJ ekspresyon düzeyi artmıştır. Artışın, özellikle östradiol (E2) ve progesteron (P4) reseptörlerini içeren uterin bezleri, uterus epiteli ile stromal hücrelerde gözlenmesi, bu artışın hiperstimülasyon sonrasında kanda artan E2 ve/veya P4 düzeyleri ilişkili olabileceğini ve uterin metabolizmayı embriyo implantasyonu için düzenleyebileceğini düşündürmüştür. Bulgularımız, bu konuda yeni çalışmaların planlanmasına temel bilgi sağlamıştır.

Keywords

• Apelin
• Apelin Reseptörü
• Kontrollü Ovaryen Hiperstimülasyon

Controlled ovarian hyperstimulation increases the expression of apelin and apelin receptor in uterus

Abstract

Objective; In this study, we investigated whether superovulation, which is frequently used in the clinic as controlled ovarian hyperstimulation, affect the expression of Apelin (APLN) and Apelin Receptor (APJ) in the uterus. Methods: Twelve female Balb-C mice 6-8 weeks old were used in this study. The groups were established as follows; virgin control female group (Knt) which did not receive any treatment, the pregnant control group (GK) which was on their pregnancy day 1, and the PMSG+hCG group (P+H) that received 5 IU/mouse/intraperitoneal (ip) PMSG and 5 IU/mouse/ip hCG . Vaginal plaque control was performed on the day after mating in the P+H and GK groups, and vaginal plaque-positive mice were accepted at day 0.5 of pregnancy. Mice in the P+H group were sacrificed 42 hours after hCG injection. Uterine tissues were obtained from all groups for immunohistochemical analysis, and paraffin sections were obtained. Adipose tissue was used as a positive control. Results: In the Knt group, APLN protein expression was present especially in the uterine glands and stromal cells that are located close to the glands. The localization of APJ protein expression was also similar to APLN. In the GK group, APLN and APJ expression levels were similar to the Knt group. However, when the localization of APJ was evaluated, it has been observed that APJ expression was intensely expressed especially in the perimetrial glands of the uterus, which was not present in the Knt group. In the P+H group, APLN expression significantly increased in the endometrial glands and stromal cells compared to the Knt and GK groups (p<0.05). Conclusions: APLN and APJ proetin expression levels increased in uterus after PMSG and hCG administration. The increase was observed especially in uterine glands, uterine epithelium and stromal cells that are known to express estradiol (E2) and progesterone (P4) receptors. Altohgether these results suggest that the increase of APLN/APJ expression in these uterin compartments may be related to the increased E2 and/or P4 levels after hyperstimulation which may also regulate metabolism of the uterus for implantation. These results provided the first basic knowledge for the possible roles of APLN/APJ system in endometrium and established the need of planning new studies on this subject.

Keywords

• Controlled Ovarian Hyperstimulation
• Apelin
• Apelin Receptor

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