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Pre- and Post-Natal Endotoxin Exposures: Effects on Leucocyte Ratios and Levels of IL-1β, TNF-, Gonadotropins and Corticosterone in Female Rats

Year 2021, Volume: 3 Issue: 3, 239 - 244, 01.09.2021
https://doi.org/10.37990/medr.891293

Abstract

Aim: The aim of this study is to investigate the long-term effects of prenatal and postnatal endotoxin exposure on hematological parameters, blood cytokines (TNF-α, IL-1β), gonadotropins and corticosterone levels in female rats.
Material and Method: Pregnant rats were injected intraperitoneally sterile saline (SF) or endotoxin (LPS) on days 17-18 of pregnancy. Following birth, female pups were subdivided into two groups and injected either sterile saline (SF, n=17) or endotoxin (LPS, n=17) on postnatal day 60 and four experimental groups were formed (SF+SF, SF+LPS, LPS+SF and LPS+LPS). Blood samples were taken 4 hours after final injection. Plasma levels of IL-1β, TNF-α, corticosteron, LH, FSH and blood leucocyte ratios were evaluated.
Results: Neutrophil % ratio was higher but lymphocyte % ratio was lower in SF+LPS, LPS+SF and LPS+LPS groups than SF+SF group. Corticosterone, LH and FSH levels were not different between the groups but TNF-α level of LPS+LPS groups was higher than SF+SF and LPS+SF groups. IL-1β level of SF+LPS group was higher than SF+SF and LPS+SF groups.
Conclusion: The results suggest that prenatal and post-pubertal endotoxin exposure programs cytokine level neutrophil and lymphocyte percentages without affecting hypothalamo-pituitary-adrenal and –gonadal axes.

Supporting Institution

İnonu University BAP

Project Number

153/2011

Thanks

This study was supported by İnonu University BAP, Turkey (#153/2011). We thank biostatisticans Prof. Dr. Saim Yologlu and Research assistant Ahmet Karaaslan for their statistical help.

References

  • Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010;327(5963):291-5.
  • Mohamadin AM, Elberry AA, Elkablawy MA, Gawad HS, Al-Abbasi FA. Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology. 2011;18(3):235-42.
  • Dong HP, Chunag IC, Wang DC, Huang LJ, Lee CI, Tsai JH, et al. Lipopolysaccharide-stimulated leukocytes contribute to platelet aggregative dysfunction, which is attenuated by catalase in rats. Kaohsiung J Med Sci. 2010;26(11):584-92.
  • Remacle C, Bieswal F, Bol V, Reusens B. Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance. Am J Clin Nutr. 2011;94(6 Suppl):1846S-52S.
  • Reusens B, Theys N, Dumortier O, Goosse K, Remacle C. Maternal malnutrition programs the endocrine pancreas in progeny. Am J Clin Nutr. 2011;94(6 Suppl):1824S-9S.
  • Hodyl NA, Krivanek KM, Lawrence E, Clifton VL, Hodgson DM. Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring. J Neuroimmunol. 2007;190(1-2):61-71.
  • Brahimi M, Osmani S, Arabi A, Enta-Soltane B, Taghezout Z, Elkahili BS, et al. The estimation of platelet count from a blood smear on the basis of the red cell: platelet ratio. Turk J Haematol. 2009;26(1):21-4.
  • Pappa A, Seferiadis K, Marselos M, Tsolas O, Messinis IE. Development and application of competitive ELISA assays for rat LH and FSH. Theriogenology. 1999;51(5):911-26.
  • Ozgocer T, Yildiz S, Elbe H, Vardi N. Endotoxin exposure and puberty in female rats: the role of nitric oxide and caspase-1 inhibition in neonates. Can J Physiol Pharmacol. 2015;93(8):603-14.
  • Wang H, Yang LL, Hu YF, Wang BW, Huang YY, Zhang C, et al. Maternal LPS exposure during pregnancy impairs testicular development, steroidogenesis and spermatogenesis in male offspring. PLoS One. 2014;9(9):e106786.
  • Bernardi MM, Kirsten TB, Matsuoka SM, Teodorov E, Habr SF, Penteado SH, et al. Prenatal lipopolysaccharide exposure affects maternal behavior and male offspring sexual behavior in adulthood. Neuroimmunomodulation. 2010;17(1):47-55.
  • Golan HM, Lev V, Hallak M, Sorokin Y, Huleihel M. Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy. Neuropharmacology. 2005;48(6):903-17.
  • Gao M, Zhang X, Chen X, Mi C, Tang Y, Zhou J, et al. Prenatal exposure to lipopolysaccharide results in local RAS activation in the adipose tissue of rat offspring. PLoS One. 2014;9(10):e111376.
  • Chen K, Geng S, Yuan R, Diao N, Upchurch Z, Li L. Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality. EBioMedicine. 2015;2(4):324-33.
  • Wei YL, Li XH, Zhou JZ. Prenatal exposure to lipopolysaccharide results in increases in blood pressure and body weight in rats. Acta Pharmacol Sin. 2007;28(5):651-6.
  • Kao SJ, Wang D, Lin HI, Chen HI. N-acetylcysteine abrogates acute lung injury induced by endotoxin. Clin Exp Pharmacol Physiol. 2006;33(1-2):33-40.
  • Doursout MF, Schurdell MS, Young LM, Osuagwu U, Hook DM, Poindexter BJ, et al. Inflammatory cells and cytokines in the olfactory bulb of a rat model of neuroinflammation; insights into neurodegeneration? J Interferon Cytokine Res. 2013;33(7):376-83.
  • Zager A, Pinheiro ML, Ferraz-de-Paula V, Ribeiro A, Palermo-Neto J. Increased cell-mediated immunity in male mice offspring exposed to maternal immune activation during late gestation. Int Immunopharmacol. 2013;17(3):633-7.
  • Luo D, Schowengerdt KO, Jr., Stegner JJ, May WS, Jr., Koenig JM. Decreased functional caspase-3 expression in umbilical cord blood neutrophils is linked to delayed apoptosis. Pediatr Res. 2003;53(5):859-64.
  • von Dadelszen P, Watson RW, Noorwali F, Marshall JC, Parodo J, Farine D, et al. Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction. Am J Obstet Gynecol. 1999;181(2):408-14.
  • Kramer BW, Kallapur SG, Moss TJ, Nitsos I, Polglase GP, Newnham JP, et al. Modulation of fetal inflammatory response on exposure to lipopolysaccharide by chorioamnion, lung, or gut in sheep. Am J Obstet Gynecol. 2010;202(1):77 e1-9.
  • Triantafilou M, Triantafilou K. The dynamics of LPS recognition: complex orchestration of multiple receptors. J Endotoxin Res. 2005;11(1):5-11.
  • Williams CL, Teeling JL, Perry VH, Fleming TP. Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring. Bmc Biol. 2011;9.
  • Enayati M, Solati J, Hosseini MH, Shahi HR, Saki G, Salari AA. Maternal infection during late pregnancy increases anxiety- and depression-like behaviors with increasing age in male offspring. Brain Res Bull. 2012;87(2-3):295-302.
  • Lasala N, Zhou H. Effects of maternal exposure to LPS on the inflammatory response in the offspring. J Neuroimmunol. 2007;189(1-2):95-101.
  • Solati J, Hajikhani R, Rashidieh B, Jalilian MF. Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring. Int J Fertil Steril. 2012;6(1):51-8.
  • Bernardi MM, Teixeira, L. P., Ligeiro-de-Oliveira, A. P., et al. Neonatal lipopolysaccharide exposure induces sexually dimorphic sickness behavior in adult rats. Psychology & Neuroscience. 2014;7(2):113-23.
  • Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I. Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci. 2011;29(6):663-71.
  • Hodyl NA, Krivanek KM, Clifton VL, Hodgson DM. Innate immune dysfunction in the neonatal rat following prenatal endotoxin exposure. J Neuroimmunol. 2008;204(1-2):126-30.

Prenatal Ve Postnatal Endotoksin Maruziyetleri: Dişi Sıçanlarda Lökosit Oranları Ve IL-1β, TNF-α, Gonadotropin Ve Kortikosteron Seviyeleri Üzerindeki Etkileri

Year 2021, Volume: 3 Issue: 3, 239 - 244, 01.09.2021
https://doi.org/10.37990/medr.891293

Abstract

Amaç: Bu çalışmanın amacı doğum öncesi ve doğum sonrası endotoksin maruziyetinin dişi sıçanlarda hematolojik parametreler, kan sitokinleri (TNF-α, IL-1β), gonadotropinler ve kortikosteron seviyeleri üzerindeki uzun vadeli etkilerini araştırmaktır.
Materyal ve Metot: Gebe sıçanlara gebeliğin 17-18. günlerinde intraperitoneal olarak steril salin (SF) veya endotoksin (LPS) enjekte edildi. Doğumdan sonra dişi yavrular iki gruba ayrılarak doğum sonrası 60. günde steril salin (SF, n= 17) veya endotoksin (LPS, n= 17) enjekte edildi ve dört deney grubu oluşturuldu (SF+SF, SF+LPS, LPS+SF ve LPS+LPS). Son enjeksiyondan 4 saat sonra kan örnekleri alındı. Plazma IL-1β, TNF-α, kortikosteron, LH, FSH düzeyleri ve kan lökosit oranları değerlendirildi.
Bulgular: Nötrofil % oranı SF+LPS, LPS+SF ve LPS+LPS gruplarında SF+SF grubuna göre daha yüksek ancak lenfosit % oranı daha düşüktü. Kortikosteron, LH ve FSH düzeyleri gruplar arasında farklı değildi ancak TNF-α düzeyleri LPS+LPS gruplarında SF+SF ve LPS+SF gruplarından daha yüksekti. SF+LPS grubunun IL-1β düzeyi SF+SF ve LPS+SF gruplarından daha yüksekti.
Sonuç: Prenatal ve post-pubertal endotoksin maruziyetinin, hipotalamo-hipofiz-adrenal ve -gonadal eksenleri etkilemeden sitokin düzeyi, nötrofil ve lenfosit yüzdelerini programladığı belirlenmiştir.

Project Number

153/2011

References

  • Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010;327(5963):291-5.
  • Mohamadin AM, Elberry AA, Elkablawy MA, Gawad HS, Al-Abbasi FA. Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology. 2011;18(3):235-42.
  • Dong HP, Chunag IC, Wang DC, Huang LJ, Lee CI, Tsai JH, et al. Lipopolysaccharide-stimulated leukocytes contribute to platelet aggregative dysfunction, which is attenuated by catalase in rats. Kaohsiung J Med Sci. 2010;26(11):584-92.
  • Remacle C, Bieswal F, Bol V, Reusens B. Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance. Am J Clin Nutr. 2011;94(6 Suppl):1846S-52S.
  • Reusens B, Theys N, Dumortier O, Goosse K, Remacle C. Maternal malnutrition programs the endocrine pancreas in progeny. Am J Clin Nutr. 2011;94(6 Suppl):1824S-9S.
  • Hodyl NA, Krivanek KM, Lawrence E, Clifton VL, Hodgson DM. Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring. J Neuroimmunol. 2007;190(1-2):61-71.
  • Brahimi M, Osmani S, Arabi A, Enta-Soltane B, Taghezout Z, Elkahili BS, et al. The estimation of platelet count from a blood smear on the basis of the red cell: platelet ratio. Turk J Haematol. 2009;26(1):21-4.
  • Pappa A, Seferiadis K, Marselos M, Tsolas O, Messinis IE. Development and application of competitive ELISA assays for rat LH and FSH. Theriogenology. 1999;51(5):911-26.
  • Ozgocer T, Yildiz S, Elbe H, Vardi N. Endotoxin exposure and puberty in female rats: the role of nitric oxide and caspase-1 inhibition in neonates. Can J Physiol Pharmacol. 2015;93(8):603-14.
  • Wang H, Yang LL, Hu YF, Wang BW, Huang YY, Zhang C, et al. Maternal LPS exposure during pregnancy impairs testicular development, steroidogenesis and spermatogenesis in male offspring. PLoS One. 2014;9(9):e106786.
  • Bernardi MM, Kirsten TB, Matsuoka SM, Teodorov E, Habr SF, Penteado SH, et al. Prenatal lipopolysaccharide exposure affects maternal behavior and male offspring sexual behavior in adulthood. Neuroimmunomodulation. 2010;17(1):47-55.
  • Golan HM, Lev V, Hallak M, Sorokin Y, Huleihel M. Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy. Neuropharmacology. 2005;48(6):903-17.
  • Gao M, Zhang X, Chen X, Mi C, Tang Y, Zhou J, et al. Prenatal exposure to lipopolysaccharide results in local RAS activation in the adipose tissue of rat offspring. PLoS One. 2014;9(10):e111376.
  • Chen K, Geng S, Yuan R, Diao N, Upchurch Z, Li L. Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality. EBioMedicine. 2015;2(4):324-33.
  • Wei YL, Li XH, Zhou JZ. Prenatal exposure to lipopolysaccharide results in increases in blood pressure and body weight in rats. Acta Pharmacol Sin. 2007;28(5):651-6.
  • Kao SJ, Wang D, Lin HI, Chen HI. N-acetylcysteine abrogates acute lung injury induced by endotoxin. Clin Exp Pharmacol Physiol. 2006;33(1-2):33-40.
  • Doursout MF, Schurdell MS, Young LM, Osuagwu U, Hook DM, Poindexter BJ, et al. Inflammatory cells and cytokines in the olfactory bulb of a rat model of neuroinflammation; insights into neurodegeneration? J Interferon Cytokine Res. 2013;33(7):376-83.
  • Zager A, Pinheiro ML, Ferraz-de-Paula V, Ribeiro A, Palermo-Neto J. Increased cell-mediated immunity in male mice offspring exposed to maternal immune activation during late gestation. Int Immunopharmacol. 2013;17(3):633-7.
  • Luo D, Schowengerdt KO, Jr., Stegner JJ, May WS, Jr., Koenig JM. Decreased functional caspase-3 expression in umbilical cord blood neutrophils is linked to delayed apoptosis. Pediatr Res. 2003;53(5):859-64.
  • von Dadelszen P, Watson RW, Noorwali F, Marshall JC, Parodo J, Farine D, et al. Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction. Am J Obstet Gynecol. 1999;181(2):408-14.
  • Kramer BW, Kallapur SG, Moss TJ, Nitsos I, Polglase GP, Newnham JP, et al. Modulation of fetal inflammatory response on exposure to lipopolysaccharide by chorioamnion, lung, or gut in sheep. Am J Obstet Gynecol. 2010;202(1):77 e1-9.
  • Triantafilou M, Triantafilou K. The dynamics of LPS recognition: complex orchestration of multiple receptors. J Endotoxin Res. 2005;11(1):5-11.
  • Williams CL, Teeling JL, Perry VH, Fleming TP. Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring. Bmc Biol. 2011;9.
  • Enayati M, Solati J, Hosseini MH, Shahi HR, Saki G, Salari AA. Maternal infection during late pregnancy increases anxiety- and depression-like behaviors with increasing age in male offspring. Brain Res Bull. 2012;87(2-3):295-302.
  • Lasala N, Zhou H. Effects of maternal exposure to LPS on the inflammatory response in the offspring. J Neuroimmunol. 2007;189(1-2):95-101.
  • Solati J, Hajikhani R, Rashidieh B, Jalilian MF. Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring. Int J Fertil Steril. 2012;6(1):51-8.
  • Bernardi MM, Teixeira, L. P., Ligeiro-de-Oliveira, A. P., et al. Neonatal lipopolysaccharide exposure induces sexually dimorphic sickness behavior in adult rats. Psychology & Neuroscience. 2014;7(2):113-23.
  • Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I. Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci. 2011;29(6):663-71.
  • Hodyl NA, Krivanek KM, Clifton VL, Hodgson DM. Innate immune dysfunction in the neonatal rat following prenatal endotoxin exposure. J Neuroimmunol. 2008;204(1-2):126-30.
There are 29 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Articles
Authors

Hilal Yıldırım 0000-0003-3971-3799

Sedat Yıldız 0000-0002-7872-790X

Tuba Özgöçer 0000-0002-4590-1342

Project Number 153/2011
Publication Date September 1, 2021
Acceptance Date May 6, 2021
Published in Issue Year 2021 Volume: 3 Issue: 3

Cite

AMA Yıldırım H, Yıldız S, Özgöçer T. Pre- and Post-Natal Endotoxin Exposures: Effects on Leucocyte Ratios and Levels of IL-1β, TNF-, Gonadotropins and Corticosterone in Female Rats. Med Records. September 2021;3(3):239-244. doi:10.37990/medr.891293

17741

Chief Editors

Assoc. Prof. Zülal Öner
Address: İzmir Bakırçay University, Department of Anatomy, İzmir, Türkiye

Assoc. Prof. Deniz Şenol
Address: Düzce University, Department of Anatomy, Düzce, Türkiye

E-mail: medrecsjournal@gmail.com

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