Annexin-2, pentraxin-3, and osteopontin expressions in the endometrium of women with idiopathic recurrent pregnancy loss during the implantation window

Abstract

Aim: Failed expression of endometrial receptivity molecules and genes during the implantation window may lead to idiopathic recurrent pregnancy loss (IRPL). The aim of this study was to investigate annexin-2 (ANXA-2), pentraxin-3 (PTX-3) and osteopontin (OPN) expressions in the endometrium of women with IRPL. Methods: A total of 34 women with IRPL and 34 age-matched healthy women were recruited in this case control study. Serum samples were collected in the mid-luteal phase of the menstrual cycle and endometrial biopsies were harvested in the window of implantation days. The expressions of ANXA-2, PTX-3, and OPN in the endometrial biopsies according to localizations were examined by immunohistochemistry. The H-score method was used to evaluate the intensity of endometrial ANXA-2, PTX-3, and OPN immune-reactivity. Results: The mean PTX-3 score was significantly higher in the epithelial endometrium of women with IRPL compared with control cases (2.47 (0.56) vs 1.44 (0.50), P<0.001). Both luminal and glandular epithelial and stromal components of the endometrium showed increased staining for PTX-3 in women with IRPL. The increase of PTX-3 expression in the epithelial endometrium correlated with the decrease of serum progesterone level (P=0.016). When ANXA-2 and OPN expressions in the epithelial endometrium of IRPL samples were compared with the age-matched control subjects, although there was lower expression, no statistically significant difference was observed (1.97 (0.71) vs 2.21 (0.59), P=0.145 and 1.97 (0.79) vs 2.12 (0.68), P=0.418). Conclusion: PTX-3 expression increases in the epithelial and stromal endometrium of women with IRPL during the implantation window. As the serum progesterone level decreases, endometrial PTX-3 expression increases in glandular and luminal epithelium in women with IRPL. Endometrial PTX-3 may be a potential molecular target for IRPL.

Keywords

• Pregnancy loss
• Annexin-2
• Endometrium
• Osteopontin
• Pentraxin-3

İdiyopatik tekrarlayan gebelik kaybı olan kadınların endometriyumunda implantasyon penceresi sırasında Annexin-2, Pentraxin-3 ve Osteopontin ekspresyonları

Öz

Amaç: İmplantasyon penceresi sırasında endometriyal reseptivite moleküllerinin ve genlerinin başarısız ekspresyonu, idiyopatik tekrarlayan gebelik kaybına (ITGK) yol açabilir. Bu çalışmanın amacı, ITGK'li kadınlarda endometriumda annexin-2 (ANXA-2), pentraxin-3 (PTX-3) ve osteopontin (OPN) ekspresyonlarını incelemekti. Yöntemler: Bu vaka kontrol çalışmasına ITGK'li toplam 34 kadın ve yaşları eşleştirilmiş 34 sağlıklı kadın dahil edilmiştir. Menstruel döngüsünün orta luteal fazında serum örnekleri toplandı ve implantasyon penceresi günlerinde endometriyal biyopsiler alındı. Endometriyal biyopsilerde lokalizasyonlara göre ANXA-2, PTX-3 ve OPN ekspresyonları immunohistokimya ile incelendi. Endometriyal ANXA-2, PTX-3 ve OPN immün reaktivitesinin yoğunluğunu değerlendirmek için H-skor yöntemi kullanıldı. Bulgular: Ortalama PTX-3 skoru, ITGK'li kadınların epitel endometriyumunda kontrol vakalarına göre anlamlı olarak daha yüksekti (2,47 (0,56)'ya karşı 1,44 (0,50), P<0,001). ITGK 'li kadınlarda endometriyumun hem luminal hem de glandüler epitel ve stromal bölümleri, PTX-3 için artmış boyanma gösterdi. Epitelyal endometriyumda PTX-3 ekspresyonundaki artış, serum progesteron seviyesindeki düşüş ile korelasyon gösterdi (P=0,016). ITGK örneklerinin epitel endometriyumundaki ANXA-2 ve OPN ekspresyonları yaşa uygun kontrol denekleriyle karşılaştırıldığında daha düşük ekspresyon görülmesine rağmen istatistiksel olarak anlamlı bir fark gözlenmedi (1,97 (0,71)'e karşı 2,21 (0,59), P=0,145 ve 1,97 (0,79)'a karşı 2,12 (0,68), P=0,418). Sonuç: İmplantasyon penceresi sırasında ITGK'li kadınların epitel ve stromal endometriyumunda PTX-3 ekspresyonu artmaktadır. ITGK'li kadınlarda serum progesteron seviyesi düştükçe glandüler ve lüminal epitelde endometrial PTX-3 ekspresyonu artmaktadır. Endometriyal PTX-3, ITGK için potansiyel bir moleküler hedef olabilir.

Anahtar Kelimeler

• Annexin-2
• Endometrium
• Osteopontin
• Pentraxin-3
• Gebelik kaybı

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