Immunohistochemical Investigation of Autophagy in the Uterus during the First Trimester of Pregnancy in Rats

Öz

During placental development, autophagy has an important role at the molecular level, especially in cases such as trophoblast cell proliferation and cell death. Abnormal placental development due to trophoblast dysfunction causes serious gynaecological diseases and various fetal malformations. In the study conducted to investigate autophagy on the 5th day of pregnancy, in the pregnant and non pregnant group uterus tissues, uterine glands LC3 and Beclin 1 (+), in the evaluation of myometrium and perimetrium, weak (+) was observed in myometrium cells in pregnancy, while (+) reaction could not be distinguished in perimetrium. In this study, it was concluded that the immunohistochemical increase in LC3 and Beclin 1 intensity in the uterus, especially in the endometrial areas in the first trimester of pregnancy compared to the control group tissues is related to the physiology of pregnancy, homeostasis in pregnancy and hormonal mechanism.

Anahtar Kelimeler

• Autophagy
• Beclin1
• LC3
• pregnancy
• rat
• uterus

Ratlarda Gebelikte Birinci Trimesterde Uterusta Otofajinin İmmunohistokimyasal Olarak Araştırılması

Öz

Plasental gelişim sırasında otofaji, özellikle trofoblast hücre proliferasyonu ve hücre ölümü gibi durumlarda moleküler düzeyde önemli bir role sahiptir. Trofoblast disfonksiyonuna bağlı anormal plasental gelişim, ciddi jinekolojik hastalıklara ve çeşitli fetal malformasyonlara neden olmaktadır. Gebeliğin 5. gününde otofajiyi araştırmak için yapılan çalışmada gebe ve gebe olmayan grupta uterus dokularında, uterus bezlerinde LC3 ve Beclin 1 (+), myometrium ve perimetriumun değerlendirilmesinde gebelikte myometrium hücrelerinde zayıf (+) gözlenirken, perimetriumda (+) reaksiyon ayırt edilememiştir. Bu çalışmada, kontrol grubu dokularına kıyasla gebeliğin ilk trimesterinde uterusta, özellikle endometrial alanlarda LC3 ve Beclin 1 yoğunluğundaki immünohistokimyasal artışın gebelik fizyolojisi, gebelikteki homeostaz ve hormonal mekanizma ile ilişkili olduğu sonucuna varılmıştır.

Anahtar Kelimeler

• Beclin1
• gebelik
• LC3
• otofaji
• rat
• uterus

Kaynakça

1. Aita VM, Liang XH, Murty VVVS et al. (1999). Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics, 59 (1), 59- 65.
2. Al Rawi S, Louvet-Vallee S, Djeddi A, et. al. (2011). Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science, 334 (6059), 1144-1147.
3. Allaire M, Rautou PE, Codogno P, Lotersztajn S (2019). Autophagy in liver diseases: Time for translation? J Hepatol, 70 (5), 985–998.
4. Arslan DÖ, Korkmaz G, Gözüaçık D (2011). Otofaji: Bir hücresel stres yanıtı ve ölüm mekanizması. AÜHSJ, 4, 184-194.
5. Chen S, Rehman SK, Zhang W et al. (2010). Autophagy is a therapeutic target in anticancer drug resistance. BBA -Reviews on Cancer, 1806 (2), 220-229.
6. Chifenti B, Locci MT, Lazzeri G et. al. (2013). Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy. Clin Exp Reprod Med, 40 (1), 33-37.
7. Curtis S, Jones CJ, Garrod A, Hulme CH, Heazell AE (2013). Identification of autophagic vacuoles and regulators of autophagy in villous trophoblast from normal term pregnancies and in fetal growth restriction. J Matern Fetal Neonatal Med, 26, 339-46.
8. Deretic V, Singh S, Master S et al. (2006). Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism. Cell Microbiol, 8, 719–727.

9. Di Bartolomeo S, Nazio F, Cecconi F (2010). The role of autophagy during development in higher eukaryotes. Traffic, 11 (10), 1280–1289.
10. Eskelinen EL (2005). Maturation of autophagic vacuoles in mammalian cells. Autophagy, 1, 1–10.
11. Fisher SJ (2015). Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol, 213 (4 Suppl), 115-122.
12. Gong JS, Kim GJ (2014). The role of autophagy in the placenta as a regulator of cell death. Clin Exp Reprod Med, 41 (3), 97-107.
13. Hung TH, Chen SF, Lo LM et al. (2012). Increased autophagy in placentas of intrauterine growthrestricted pregnancies. PLoS One, 7 (7), e40957.
14. Kim DH, Sarbassov DD, Ali SM et. al. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell, 110 (2), 163-175.
15. Mooren FC, Krüger K (2015). Exercise, autophagy, and apoptosis. Progress in Molecular Biology and Translational Science, C. Bouchard (Ed.). 407-422.
16. Mortensen M, Ferguson DJ, Simon AK (2010). Mitochondrial clearance by autophagy in developing erythrocytes: clearly important, but just how much so? Cell Cycle, 9, 1901–1906.
17. Munz C (2006). Autophagy and antigen presentation. Cell Microbiol, 8, 891–898.
18. Oh SY, Choi SJ, Kim KH et al. (2008). Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. Reprod Sci, 15, 912-920.
19. Ozpolat B, Benbrook DM (2015). Targeting autophagy in cancer management-stragies and development. Cancer Manag Res, 7, 291-299.
20. Pan YJ, He L, Zhou SJ et al. (2018). Expression of urotensin II is associated with placental autophagy in patients with severe preeclampsia. J Hum Hypertens, 32 (11), 759-769.
21. Rubinsztein DC, Difiglia M, Heintz N et. al. (2005). Autophagy and its possible roles in nervous system diseases, damage and repair Autophagy, 1, 11–22.
22. Sato M, Sato K (2011). Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science, 334, 1141-1144.
23. Song WH, Yi YJ, Sutovsky M, Meyers S, Sutovsky P (2016). Autophagy and ubiquitin-proteasome system contribute to sperm mitophagy after mammalian fertilization. Proc Natl Acad Sci, 113 (36), e526-570.
24. Stitzel ML, Seydoux G (2007). Regulation of the oocyte-to-zygote transition. Sci, 316 (5823), 407–408.
25. Tatar M, Tufekci KK, Uslu S, Öner J (2023). Expression of ADAMTS 1-4-8 and placental growth factor in ovary and oviduct during pregnancy in the first trimester. Anat Histol Embryol, 52 (4), 619-626.
26. Xie Z, Klionsky DJ (2007). Autophagosome formation: core machinery and adaptations. Nat Cell Biol, 9 (10), 1102.
27. Wileman T (2006). Aggresomes and autophagy generate sites for virus replication. Sci, 312, 875–878.
28. Wirawan E, Lippens S, Vanden Berghe T et al. (2012). Beclin1: a role in membrane dynamics and beyond. Autophagy, 8, 6-17.
29. Yang YP, Liang ZQ, Gu ZL, Qin ZH (2005). Molecular mechanism and regulation of autophagy. Acta Pharmacol Sin, 26 (12), 1421-1434.
30. Yang P, Li ZQ, Tye KD et. al. (2020). Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy. BMC Pregnancy Childbirth, 20, 216.
31. Yoshida GJ (2017). Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. J Hematol Oncol, 10, 67.