Nihan SEMERCİ, Gökçen BİLİCİ, Filiz YILMAZ, Zahide ÇAVDAR, Uygar SACIK, Ümit KAYIŞLI, Güven ERBİL

THE EFFECTS OF IMMOBILIZATION STRESS ON PLACENTA AND FETUS IN PREGNANT MICE

ObjectiveStress can affect negatively mother and fetuses during pregnancy. We aimed to investigate the effects ofchronic immobilization stress on placental maturationand fetal development.Materials And MethodsBalb/c virgin female mice (20-30 g) were mated withmale mice in a 2 to 1 female to male ratio. Pregnantmice in control group (n=6) were left undisturbed,whereas pregnant mice in the stress group (n=6)were exposed to 45 min chronic immobilization stressfor three times/day starting from gestational day 6 till18. Fetuses and placentas were removed from damson the gestational day 18 under anesthesia.ResultsThe prenatal stress significantly increased apoptosisin several placental cells including trophoblastic giantcells, glycogen cells and labyrinth trophoblastic cells and resulted in intrauterine growth restriction. Thestress caused a decreased superoxide dismutaseand glutathione levels. Alizarin Red S staining showsthe ossification center of the fetuses to see developmental abnormality.ConclusionGestational stress causes placental dysfunctions bytriggering apoptosis, reducing the labyrinth zone aswell as increasing collagen levels, which may impairfetal development that may contribute to pathogenesis of intrauterine growth restriction.

FARE GEBELİK DÖNEMİNDE HAREKETSİZLİK STRESİNİN PLASENTA VE YAVRUYA ETKİLERİ

Amaç Stres gebelik sürecinde anne ve fetüs sağlığını olumsuz etkilemektedir. Çalışmamızda kronik hareketsizlik stresinin plasenta ve fetüs gelişimi üzerine etkilerini araştırmayı hedefledik. Gereç ve Yöntem Balb/c suşu dişi fareler (20-30gr), 2dişi-1erkek olacak şekilde katıma alındı. Kontrol grubundaki (n=6) gebe farelere herhangi bir uygulama yapılmazken, stres grubundaki (n=6) gebe farelere gebeliğin 6.gününden 18.gününe kadar günde 3 defa 45dakikalık kronik hareketsizlik stresine maruz bırakıldı. Gebeliğinin 18. Gününde plasenta ve fetüsler anestezi altında sezaryen ile alındı. Bulgular Prenatal stres, trofoblastik dev hücreler, glikojen içeren hücreler ve labirent trofoblastik hücreler dahil olmak üzere birçok plasental hücrede apoptozu önemli ölçüde arttırdı ve intrauterin büyüme geriliğine sebep oldu. Stres süperoksit dismutaz ve glutatyon seviyelerini azalttı. Fetüsün gelişimini değerlendirmek için, Alizarin Red S boyaması ile fetüsün kemikleşme merkezleri değerlendirildi. Sonuç Gebelik sürecindeki stres, apoptozu tetikleyerek, labirent bölgesi küçüldü ve plasenta yetmezliğine sebep oldu, ayrıca kollajen seviyelerini arttırarak fetüs gelişimini olumsuz yönde etkileyerek intrauterin büyüme geriliği patogenezinde katkısı olduğunu gözlemledik. Keywords: Fetus; hareketsizlik stresi; plasenta.

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1. Watson ED, Cross JC. Development of structures and transport functions in the mouse placenta, Physiology (Bethesda). 2005 Jun;20:180-93.

2. Jefferey MR, Yasuhiro Y, Monika AW, Abby CC. Placental inflammation and oxidative stress in the mouse model of assisted reproduction, Placenta. 2011 Nov; 32(11): 852–858. Published online 2011 Sep 1. doi: 10.1016/j.placenta.2011.08.003

3. Herman, J.P., Mcklveen J.M., Ghosal S. et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response, Compr. Physiol. 6 (2016) 603–621. doi:10.1002/cphy.c150015.

4. Harris R.B.S., Chronic and acute effects of stress on energy balance: are there appropriate animal models?, Am. J. Physiol. - Regul. Integr. Comp. Physiol. 308 (2015) R250–R265. doi:10.1152/ajpregu.00361.2014.

5. Perkinsa G., Bossy-Wetzelb E., Ellisman M.H., New Insights into Mitochondrial Structure during Cell Death, Exp. Neurol. 218 (2010) 183–192. doi:10.1016/j.expneurol.2009.05.021.

6. Straszewski-Chavez S.L., Abrahams V.M., Mor G., The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy, Endocr. Rev. 26 (2005) 877–897. doi:10.1210/er.2005-0003.

7. Uckan D., Steele A., Cherry et al. Trophoblasts express Fas ligand: a proposed mechanism for immune privilege in placenta and maternal invasion., Mol. Hum. Reprod. 3 (1997) 655–662. doi:10.1093/molehr/3.8.655.

8. Huppertz B., Frank H.G., Kingdom J.C.P., Reister F., Kaufmann P., Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta, Histochem. Cell Biol. 110 (1998) 495–508. doi:10.1007/s004180050311.

9. Demir R., İnsan plasentasında ışık mikroskobu, tarayıcı elektron mikroskobu bulguları ve ikizlerde perfüzyon incelemeleri, 1978.

10. Burtis C.A., Ashwood E.R., Tietz textbook of clinical chemistry, W.B. Saunders Company, Pennsylvania, 1994.

11. Benirschke K., The placenta in the litigation process, Am. J. Obstet. Gynecol. 162 (1990) 1445–1450. doi:10.1016/0002-9378(90)90904-L.

12. Benirschke K., Kaufmann P., Baergen R.N., Abortion, placentas of trisomies, and immunologic considerations of recurrent reproductive failure, in: Pathol. Hum. Placenta, 2006: pp. 762–796.

13. Kaufmann P., Demonstration os cytoplasmic polyps from the human trophoblast by scanning electron microscopy, Arch. Gynakol. 211 (1970) 523.

14. Schulze B., Schlesinger C., Miller K., Chromosomal mosaicism confined to chorionic tissue, Prenat. Diagn. 7 (1987) 451–453. doi:10.1016/j.ajpath.2011.02.031.

15. Demir R., Demir A.Y, Yinanc M., Structural changes in placental barrier of smoking mother a quantitative and ulstrastructural study, Pathol. - Res. Pract. 190 (1994) 656–667. doi:10.1016/ S0344-0338(11)80744-2.

16. Rassoulzadegan M., Rosen B.S., Gillot I., Cuzin F., Phagocytosis reveals a reversible differentiated state early in the development of the mouse embryo., EMBO J. 19 (2000) 3295–3303. doi:10.1093/emboj/19.13.3295.

17. El-Hashash A.H.K., Warburton D., Kimber S.J., Genes and signals regulating murine trophoblast cell development, Mech Dev. 127 (2010) 1–20. doi:10.1007/s11103-011-9767-z.Plastid.

18. Chakraborty D., Rumi M.A.K., Soares M.J., NK cells, hypoxia and trophoblast cell differentiation, Cell Cycle. 11 (2012) 2427– 2430. doi:10.4161/cc.20542.

19. Nadeau V., Bissonauth V., Charron J., Le rôle des kinases Mek1 et Mek2 dans la formation de la barrière hématoplacentaire chez la souris, (2012).

20. Girardin F., Membrane transporter proteins: A challenge for CNS drug development, Dialogues Clin. Neurosci. 8 (2006) 311–321. doi:10.1016/0266-7681(94)90280-1.

21. Wataganara T., Bianchi D.W., Fetal cell-free nucleic acids in the maternal circulation: New clinical applications, Ann. N. Y. Acad. Sci. 1022 (2004) 90–99. doi:10.1196/annals.1318.015.

22. Gavrieli Y., Sherman Y., Ben-Sasson S.A., Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation, J. Cell Biol. 119 (1992) 493–501. doi:10.1083/ jcb.119.3.493.

23. D’mello A.P., Liu Y., Effects of maternal immobilization stress on birth weight and glucose homeostasis in the offspring, Psychoneuroendocrinology. 31 (2006) 395–406. doi:10.1016/j. psyneuen.2005.10.003.

24. Molehin D., Dekker Nitert M., Richard K., Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism, J. Thyroid Res. 2016 (2016). doi:10.1155/2016/8765049.

25. Mairesse J., Lesage J., Breton C., et al. Maternal stress alters endocrine function of the feto-placental unit in rats, AJP Endocrinol. Metab. 292 (2007) E1526–E1533. doi:10.1152/ajpendo.00574.2006.

26. Morrison J.L., Sheep models of intrauterine growth restriction: Fetal adaptations and consequences, Clin. Exp. Pharmacol. Physiol. 35 (2008) 730–743. doi:10.1111/j.1440- 1681.2008.04975.x.

27. Jang E.A., Longo L.D., Goyal R., Antenatal maternal hypoxia: criterion for fetal growth restriction in rodents., Front. Physiol. 6 (2015) 176. doi:10.3389/fphys.2015.00176.

28. Dimasuay K.G., Boeuf P., Powell T.L., Jansson T., Placental responses to changes in the maternal environment determine fetal growth, Front. Physiol. 7 (2016) 1–9. doi:10.3389/fphys.2016.00012.

29. Gundogan F., Elwood G., Mark P., Feijoo A., Longato L., Ethanol-induced oxidative stress and mitochondrial dysfunction in rat placenta: Relevance to Pregnancy Loss, Alcohol. Clin. Exp. Res. 34 (2010) 415–423. doi:10.1111/j.1530-0277.2009.01106 .x.Ethanol-Induced.

30. Neale D.M., Mor G., The role of Fas mediated apoptosis in preeclampsia, J. Perinat. Med. 33 (2005) 471–477. doi:10.1515/ JPM.2005.085.

31. Yasemin Aksoy, The Role Of Glutathıone In Antıoxıdant Mechanısm, Turkiye Klinikleri J Med Sci. 2002;22(4):442-8.

32. Murat Baflar, Mehmet Türker, Tülay İrez, Oktay Arda, Süperovulasyon Protokolünde Kullanılan GnRH Agonistinin Oosit Olgunluğu ve Çapına Etkileri, Cerrahpaşa Tıp Dergisi 2008; 39(2): 41-48 ISSN: 1300-5227.

33. Erica D. Watson, James C. Cross, Development of Structures and Transport Functions in the Mouse Placenta, Physiology (Bethesda). 2005 Jun;20:180-93.