The Effect of Low Molecular Weight Heparins on Placentation: A Rat Model Study

Yıl 2022, Cilt: 43 Sayı: 4, 564 - 568, 27.12.2022

Gülizar Özer Çağlar Yıldız Hatice Özer Ali Çetin

https://doi.org/10.17776/csj.1169083

Öz

Low molecular weight heparins (LMWHs) have been used for the treatment for recurrent pregnancy loss (RPL) for a long time. We aimed to investigate the efficacy of the LMWHs on angiogenesis and apoptosis during placentation. A total of twenty-four rats were randomly divided into three groups each containing 8 rats: normal saline; enoxaparine sodium 0.4 ml, and enoxaparine sodium 0.8 ml were given to the Group 1, 2 and 3, respectively. Normal saline and enoxaparine sodium 0.4 ml or 0.8 ml were given to the rats beginning on the day the pregnancy was detected and continued until the 15th day of the pregnancy. The tissues containing placental decidual zone were immunostained for vascular endothelial growth factor A (VEGF-A) and caspase 7. The decidual and placental VEGF-A and the decidual caspase 7 immunostaining scores of all of the groups were high, however, there were no statistically significant differences among the groups (p>0.05). On the other hand, the placental caspase 7 immunostaining scores of the normal saline group were significantly lower than those of the enoxaparine sodium 0.4 and the enoxaparine sodium 0.8 groups (p<0.05). LMWHs seem to have effects on placental angiogenesis and apoptosis.

Anahtar Kelimeler

Low molecular weight heparin, Placenta, Angiogenesis, Apoptosis.

Kaynakça

• [1] Bick R.L., Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group, Clin. Appl. Thromb. Hemost., 6 (3) (2000) 115-125.
• [2] Ford H. B., Schust D. J., Recurrent pregnancy loss: etiology, diagnosis, and therapy, Rev. Obstet. Gynecol., 2 (2) (2009) 76-83.
• [3] Greer I.A., Inherited thrombophilia and venous thromboembolism. Best Pract. Res. Clin. Obstet. Gynaecol., 17 (3) (2003) 413-425.
• [4] Robertson L., Wu O., Langhorne P., Twaddle S., Clark P., Lowe G.D.O., Walker I.D., Greaves M., Brenkel I., Regan L., Greer I. A., for TheThrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study, Thrombophilia in pregnancy: a systematic review, Br. J. Haematol., 132 (2) (2006) 171-196.
• [5] Blumenfeld Z., Brenner B., Thrombophilia-associated pregnancy wastage, Fertil. Steril., 72 (5) (1999) 765-774.
• [6] Ingman K., Cookson V.J.K.W., Jones C.J.P., Aplin J.D., Characterisation of hofbauer cells in first and second trimester placenta: incidence, phenotype, survival in vitro and motility, Placenta, 31 (6) (2010) 535-544.
• [7] Poole, T.J., Coffin, J. D., Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern, J. Exp. Zool., 251 (2) (1989) 224-231.
• [8] Speroff L., Fritz M.A., In: Taylor, H.S. (Ed). Klinik Jinekolojik Endokrinoloji ve İnfertilite. 7th ed. İstanbul: Güneş Kitabevi (2007).
• [9] Toder V., Carp H., Fein A. Torchinsky A., The role of pro- and antiapoptotic molecular interactions in embryonic maldevelopment, Am J Reprod Immunol., 48 (4) (2002) 235-244.
• [10] Pierangeli S.S., Pojen P.C., Raschi E., Scurati S., Grossi C., Borghi M.O., Palomo I., Harris E.N., Meroni P.L., Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms, Semin. Thromb. Hemost,, 34 (3) (2008) 236-250.
• [11] Berker B., Cengiz L., Gestasyonel Trombofili, Maternal Fetal Tıp & Perinatoloji, (13) (2001) 725-729.
• [12] Brenner B., Hoffman R., Blumenfeld Z., Weiner Z., Younis J.S., Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin, Thromb. Haemost., 83 (05) (2000) 693-697.
• [13] Price G.C., Thompson S.A, Kam P.C.A., Tissue factor and tissue factor pathway inhibitor, Anaesthesia, 59 (5) (2004) 483-492.
• [14] Mätzsch T., Bergqvist D., Hedne U., Ostergaard P., Effects of an enzymatically depolymerized heparin as compared with conventional heparin in healthy volunteers, Thromb. Haemost., 57 (01) (1987) 97-101.
• [15] Watson E.D., Cross J.C., Development of structures and transport functions in the mouse placenta, Physiology, 20 (3) (2005) 180-193.
• [16] Brosens I., Pijnenborg, R., Vercruysse L., Romero R., The “Great Obstetrical Syndromes” are associated with disorders of deep placentation, Am. J. Obstet. Gynecol., 204 (2011) 193–201.
• [17] Creeth H.D.J., John R.M., The placental programming hypothesis: placental endocrine insufficiency and the co-occurrence of low birth weight and maternal mood disorders, Placenta, 98 (2020) 52–59.
• [18] Davies J.E., Pollheimer J., Yong H.E.J., et al., Epithelial-mesenchymal transition during extravillous trophoblast differentiation, Cell Adh. Migr., 10 (3) (2016) 310-321.
• [19] İrtegün S., Ağaçayak E., Deveci E., Preeklamptik ve normotansif plasentalarda VEGF ve Vimentin ekspresyon düzeylerinin immunohistokimya ve Western Blot yöntemleri ile incelenmesi, Dicle Tıp Derg., 43 (3) (2016) 400-405.
• [20] Flint E.J., Cerdeira A.S., Redman C.W., Vatish M., The role of angiogenic factors in the management of preeclampsia, Acta Obstet Gynecol Scand , 98 (6) (2019) 700-707.
• [21] Lunghi L., Ferretti M. E., Medici S., Biondi C., Vesce F., Control of human trophoblast function, Reprod. Biol. Endocrinol., 5 (6) (2007) 1-14.
• [22] Deruelle P., Coulon C., The use of low molecular weight heparins in pregnancy, how safe are they? Curr. Opin. Obstet. Gynecol., 19 (6) (2007) 573-577.
• [23] De Carolis S., Ferrazzani S., De Stefano V., Garofalo S., Fatigante G., Rossi E., Leone G., Caruso A., Inherited thrombophilia: treatment during pregnancy, Fetal. Diagn. Ther., (21) (2006) 281-286.
• [24] Di Simone N., Di Nicuolo F., Sanguinetti M., Ferrazzani S., D'Alessio M. C., Castellani R., Bompiani A., Caruso A., Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors, Placenta, 28 (4) (2007) 298-304.
• [25] Monien S., Kadecki O., Baumgarten S., Salama A., Dörner T., Kiesewetter H., Use of heparin in women with early and late miscarriages with and without thrombophilia, Clin. Appl. Thromb. Hemost., 15 (6) (2009) 636-644.
• [26] Sarto A., Rocha M., Geller M., Capmany C., Martinez M., Quintans C., Donaldson M., Pasqualini R. S., Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia, Medicina, 61 (4) (2001) 406-412.
• [27] Sobel M.L., Kingdom J., Drewlo S., Angiogenic response of placental villi to heparin, Obstet. Gynecol., 117 (6) (2011) 1375-1383.
• [28] Xia H.F., Sun J., Sun Q. H., Yang Y., Peng J.P., Implantation-associated gene-1 (Iag-1): a novel gene involved in the early process of embryonic implantation in rat, Hum. Reprod., 23 (7) (2008) 1581-1593.
• [29] Perez M.J., Macias R.I.R., Marin J.J.G., Maternal cholestasis induces placental oxidative stress and apoptosis. Protective effect of ursodeoxycholic acid, Placenta, 27 (1) (2006) 34-41.
• [30] Yuan Z., Mei Z., Fengyan Liu., Low molecular weight heparin inhibits cell apoptosis in the placenta of rats with preeclampsia-like symptoms. Nan Fang Yi Ke Da Xue Xue Bao, 32 (6) (2012) 862-6.
• [31] Fox H., Wells M., Haines and Taylor, Obstetrical and Gynaecological Pathology.4 th ed. Churchill Livingstone; (1995).
• [32] Battistelli M., Burattini S., Pomini F., Scavo M., Caruso A., Falcieri E., Ultrastructural study on human placenta from intrauterin growth retardation cases, Micros. Res. Tech., 65 (2004) 150-158.
• [33] Altshuler G., A conceptual approach to placental pathology and pregnancyoutcome, Semin. Diagn. Pathol., 10(3) (1993) 204-221.