Transforming Growth Factor-beta and Liver Injury in an Arginine Vasopressin-induced Pregnant Rat Model

Overview

Journal Clin Exp Reprod Med

Date 2021 May 24

PMID 34024085

Citations 1

Authors

Nalini Govender

Sapna Ramdin

Rebecca Reddy

Thajasvarie Naicker

Affiliations

Soon will be listed here.

Abstract

Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model.

Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats.

Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group.

Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.

Citing Articles

The Clinical Value of Rodent Models in Understanding Preeclampsia Development and Progression.

Ramdin S, Baijnath S, Naicker T, Govender N Curr Hypertens Rep. 2023; 25(6):77-89.

PMID: 37043097 PMC: 10172248. DOI: 10.1007/s11906-023-01233-9.

References

Valensise H, Vasapollo B, Gagliardi G, Novelli G . Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension. 2008; 52(5):873-80. DOI: 10.1161/HYPERTENSIONAHA.108.117358. View

Levine R, Maynard S, Qian C, Lim K, England L, Yu K . Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350(7):672-83. DOI: 10.1056/NEJMoa031884. View

Shekhar S, Diddi G . Liver disease in pregnancy. Taiwan J Obstet Gynecol. 2015; 54(5):475-82. DOI: 10.1016/j.tjog.2015.01.004. View

August P, LEVENTHAL B, Suthanthiran M . Hypertension-induced organ damage in African Americans: transforming growth factor-beta(1) excess as a mechanism for increased prevalence. Curr Hypertens Rep. 2000; 2(2):184-91. DOI: 10.1007/s11906-000-0080-5. View

Scroggins S, Santillan D, Lund J, Sandgren J, Krotz L, Hamilton W . Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia. Clin Sci (Lond). 2018; 132(3):419-436. PMC: 5947858. DOI: 10.1042/CS20171059. View

Lyall F, Simpson H, Bulmer J, Barber A, Robson S . Transforming growth factor-beta expression in human placenta and placental bed in third trimester normal pregnancy, preeclampsia, and fetal growth restriction. Am J Pathol. 2001; 159(5):1827-38. PMC: 1867050. DOI: 10.1016/s0002-9440(10)63029-5. View

Sandgren J, Deng G, Linggonegoro D, Scroggins S, Perschbacher K, Nair A . Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice. JCI Insight. 2018; 3(19). PMC: 6237463. DOI: 10.1172/jci.insight.99403. View

Dixon T, PURDOM M . Serum 5-nucleotidase. J Clin Pathol. 1954; 7(4):341-3. PMC: 1023849. DOI: 10.1136/jcp.7.4.341. View

Brown M, Magee L, Kenny L, Karumanchi S, McCarthy F, Saito S . Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension. 2018; 72(1):24-43. DOI: 10.1161/HYPERTENSIONAHA.117.10803. View

10.

Froese A, Shimbori C, Bellaye P, Inman M, Obex S, Fatima S . Stretch-induced Activation of Transforming Growth Factor-β1 in Pulmonary Fibrosis. Am J Respir Crit Care Med. 2016; 194(1):84-96. DOI: 10.1164/rccm.201508-1638OC. View

11.

Lafontaine L, Chaudhry P, Lafleur M, Van Themsche C, Soares M, Asselin E . Transforming growth factor Beta regulates proliferation and invasion of rat placental cell lines. Biol Reprod. 2010; 84(3):553-9. PMC: 6366158. DOI: 10.1095/biolreprod.110.086348. View

12.

Li Q . Transforming growth factor β signaling in uterine development and function. J Anim Sci Biotechnol. 2014; 5(1):52. PMC: 4255921. DOI: 10.1186/2049-1891-5-52. View

13.

Gowda S, Desai P, Hull V, Math A, Vernekar S, Kulkarni S . A review on laboratory liver function tests. Pan Afr Med J. 2011; 3:17. PMC: 2984286. View

14.

Caniggia I, Kuliszewsky M, Post M, Lye S . Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest. 1999; 103(12):1641-50. PMC: 408387. DOI: 10.1172/JCI6380. View

15.

Hyder M, Hasan M, Mohieldein A . Comparative Study of 5'-Nucleotidase Test in Various Liver Diseases. J Clin Diagn Res. 2016; 10(2):BC01-3. PMC: 4800507. DOI: 10.7860/JCDR/2016/12754.7163. View

16.

Munder M, Eichmann K, Moran J, Centeno F, Soler G, Modolell M . Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J Immunol. 1999; 163(7):3771-7. View

17.

Bronte V, Zanovello P . Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. 2005; 5(8):641-54. DOI: 10.1038/nri1668. View

18.

Drawz P, Rosenberg M . Slowing progression of chronic kidney disease. Kidney Int Suppl (2011). 2014; 3(4):372-376. PMC: 4089661. DOI: 10.1038/kisup.2013.80. View

19.

Landmesser U, Drexler H . Endothelial function and hypertension. Curr Opin Cardiol. 2007; 22(4):316-20. DOI: 10.1097/HCO.0b013e3281ca710d. View

20.

Toporsian M, Gros R, Kabir M, Vera S, Govindaraju K, Eidelman D . A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res. 2005; 96(6):684-92. DOI: 10.1161/01.RES.0000159936.38601.22. View