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. 2026 Mar 5;23(1):56-63.
doi: 10.4274/tjod.galenos.2025.93630. Epub 2026 Jan 29.

The effect of tinzaparin sodium and leuprolide acetate in an experimental mouse model of endometriosis: The rol of the WNT/beta-catenin pathway

Yasemin Albak  1 , Gamze Sönmez Ünal  2 , Çağlar Yıldız  3 , Meral Çetin  4 , Sevgi Durna Daştan  5 , Erkan Gümüş  6 , Ahmet Şevki Taşkıran  7 , Ali Çetin  8
Affiliations

The effect of tinzaparin sodium and leuprolide acetate in an experimental mouse model of endometriosis: The rol of the WNT/beta-catenin pathway

Yasemin Albak et al. Turk J Obstet Gynecol. .

Abstract
in English, Turkish

Objective: Endometriosis is a benign condition driven by estrogen and inflammation in which endometrial-like tissue develops in ectopic locations. We aimed to determine whether non-steroidal agents acting on the WNT/beta-catenin signaling axis could provide therapeutic benefit in this disease.

Materials and methods: Forty adult female mice underwent surgical creation of endometriotic implants and were then distributed into five experimental arms: untreated controls, early leuprolide (leup1d), early tinzaparin (tnz1d), delayed leuprolide (leup7d), and delayed tinzaparin (tnz7d). Early treatment groups received drug treatment beginning at postoperative hour 24, whereas delayed groups began treatment on postoperative day 8. At two weeks post-surgery, lesions were harvested for RNA extraction and transcript profiling. Tissues were also processed for hematoxylin-eosin staining with semi-quantitative grading. Immunostaining was performed using antibodies against HIF1a and WNT2.

Results: The tnz7d group exhibited decreased inflammatory markers, while the leup7d group displayed reduced epithelial content; both changes resulted in lower disease severity scores. WNT2 and HIF1a immunostaining revealed greater reductions in score in the tnz7d group compared with controls and other treatment arms, but these differences were not statistically significant.

Conclusion: Further investigation is warranted to determine how tinzaparin sodium and leuprolide acetate modulate the WNT/β-catenin axis for the management of endometriosis.

Amaç: Endometriozis, iyi huylu, östrojen bağımlı bir enflamatuvar hastalık olup, ektopik endometriyal implantlarla karakterizedir. Bu çalışma, insanlarda endometriozis tedavisi için WNT/beta-katenin yoluna odaklanan yeni non-steroid ilaçların potansiyelini araştırmayı amaçlamıştır.

Gereç ve yöntemler: Çalışmaya 40 yetişkin dişi fare dahil edilmiştir. Farelerde cerrahi olarak endometriotik odaklar oluşturulduktan sonra, fareler rastgele beş gruba ayrıldı: 1- Kontrol, 2- Profilaktik leuprolid asetat grubu (leup1d), 3- Profilaktik tinzaparin sodyum grubu (tnz1d), 4- Terapötik leuprolid asetat grubu (leup7d), 5- Terapötik tinzaparin sodyum grubu (tnz7d). Leup1d ve tnz1d gruplarına ameliyat sonrası 24. saatten itibaren profilaktik dozlarda ilaçlar verildi. Leup7d ve tnz7d gruplarına ise ameliyat sonrası 8. günden itibaren terapötik dozlarda ilaçlar verildi. Ameliyat sonrası 14. günde, çıkarılan endometriotik odaklar üzerinde toplam RNA izolasyonu ve gen ekspresyonu analizleri yapıldı. Ek olarak, odaklar hematoksilen ve eozin ile boyandı ve endometriozis için yarı kantitatif olarak puanlandı. HIF1a ve WNT2 için birincil antikorlar kullanılarak immünohistokimyasal analiz yapıldı.

Bulgular: Tinzaparin 7 günlük grupta enflamasyonda azalma görülürken, leuprolid 7 günlük grupta epitel dokusunda azalma görülmüş ve bu da endometriozis skorunda düşüşe yol açmıştır. WNT2 ve HIF1a ile yapılan immünohistokimyasal boyama, kontrol grubu ve diğer gruplara kıyasla tinzaparin 7 günlük grupta endometriozis skorunda daha belirgin bir azalma olduğunu göstermiştir, ancak bu istatistiksel olarak anlamlı değildir.

Sonuç: Endometriozis tedavisinde tinzaparin sodyum ve leuprolid asetatın WNT/beta-katenin yolakları üzerindeki etkilerini doğrulamak için daha fazla çalışma yapılması gerekmektedir.

Keywords: Endometriosis; WNT/beta-catenin pathway; immunohistochemistry; leuprolide acetate; tinzaparin sodium.

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Conflict of interest statement

No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
Transcript abundance profiles for control, leu1d, leu7d, tnz1d, and tnz7d groups encompassing WNT2, HIF1a, and related pathway components. Values represent the median and interquartile range
Figure 2
Figure 2
Histological and immunohistochemical findings in endometriotic foci following tinzaparin sodium and leuprolide acetate administration EF: Endometriotic foci, X20: 20-fold optical magnification
Figure 3
Figure 3
Disease severity scores and immunostaining indices across all experimental groups (control, tnz1d, tnz7d, leup1d, leup7d). Data are shown as median (interquartile range). Inflammatory scores in tnz7d were significantly reduced compared with controls (designated ‘a’; p<0.05), and epithelial scores in leup7d were significantly decreased compared with the control and tnz1d groups (designated ‘b’; p<0.05)
See this image and copyright information in PMC

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