Impact of Antenatal Steroid Treatment on External Morphological Feature of Newly Born Rats
Keywords:
Prenatal glucocorticoids, Dexamethasone, Hydrocortisone, Fetal growth retardation, Congenital anomaliesAbstract
This paper is about the application of Steroid treatment during pregnancy as practiced in common in practice, in rheumatological and autoimmune diseases, its prolonged use has an adverse effect on fetal growth. The study aimed to assess the effect of prenatal dexamethasone and hydrocortisone treatment on rats' offspring concerning growth parameters, congenital malformation, and survival rate. Sixty pregnant rats were allocated into 12 groups, and administered intraperitoneally either dexamethasone (1mg/kg/day) or hydrocortisone (9 mg/kg/day), and a control group that received normal saline. These were administered in the first week or last week of gestation. Neonatal body weight, length, and gross morphological anomalies were evaluated postnatal at 1 and 15 days. Prenatal dexamethasone treatment in late pregnancy resulted in 27 % neonatal mortality on day 3. Dexamethasone and hydrocortisone significantly reduced body weight and length of neonates compared to the control group, which is more prominent in dexamethasone treatment. However, both glucocorticoids resulted in profound developmental deficits when given in late pregnancy, especially dexamethasone, which causes profound growth retardation and teratogenic effects in neonates. At the same time hydrocortisone has a less severe impact on postnatal malformations and growth retardation. This sheds more light on the timing of steroid administration during the prenatal period, which should be taken into consideration for risk-benefit assessment.
References
[1] Xiao, W.l.; Liu, X.Y.; Liu, Y.S.; Zhang, D.Z.; Xue, L.F.; "The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis". Reprod Toxicol., 69:99-105, 2017. DOI: https://doi.org/10.1016/j.reprotox.2017.02.006
[2] Fahmy, S.G.; Al-Amgad, Z.; Abdallah, R.M.; Rehan, I.F.; Mahmoud, F.A.; Mahmoud, M.; "Effect of Sustained Dexamethasone Treatment on Anxiety and Depression-related Behaviors in Pregnant Rats". Sohag J Sci, 10(1): 137-43, 2025. DOI: 10.21608/sjsci.2025.338539.1236
[3] Kataja, E.L.; Rodrigues, A.J.; Scheinin, N.M.; Nolvi S, Korja, R.; Häikiö, T.; Ekholm, E.; et al.; "Prenatal Glucocorticoid-Exposed Infants Do Not Show an Age-Typical Fear Bias at 8 Months of Age–Preliminary Findings From the FinnBrain Birth Cohort Study". Front. Psychol., 12: 655654, 2021. DOI: https://doi.org/10.3389/fpsyg.2021.655654
[4] Fowden, A.L.; Vaughan, O.R.; Murray, A.J; Forhead, A.J; "Metabolic consequences of glucocorticoid exposure before birth". Nutrients., 14(11):2304, 2022. DOI: https://doi.org/10.3390/nu14112304
[5] Van den Bergh, B.R.; van den Heuvel, M.I.; Lahti, M.; Braeken, M.; de Rooij, S.R.; Entringer, S.; Hoyer, D.; et al.; "Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy". Neurosci Biobehav Rev., 117:26-64, 2020. DOI: https://doi.org/10.1016/j.neubiorev.2017.07.003
[6] Al-Shammary, Z.A.; Sally, A.; Sabti, Z.S.; Jouda, J.; Hameid, S.A.; "The Effect of Acute and Chronic Noise Stress Exposure on some Physiological and Immunological Parameters in Male and Female Adult Mice". Al-Nahrain J. Sci, 27(2):127-32, 2024. DOI: https://doi.org/10.22401/chej3z39
[7] Rakers, F.; Schleussner, E.; Cornelius, A.; Kluckow, S.; Muth, I.; Hoyer, D.; Rupprecht, S.; et al.; "Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study". Acta Obstet Gynecol Scand, 103(8):1530-40, 2024. DOI: https://doi.org/10.1111/aogs.14885
[8] Laugesen, K.; Sørensen, H.T.; Jørgensen, JOL.; Petersen, I.; "In utero exposure to glucocorticoids and risk of anxiety and depression in childhood or adolescence". Psychoneuroendocrinology, 141: 105766, 2022.DOI: https://doi.org/10.1016/j.psyneuen.2022.105766
[9] Korgun, E.T.; Ozmen, A.; Unek, G.; Mendilcioglu, I.; "The effects of glucocorticoids on fetal and placental development". In: Glucocorticoids - New Recognition of Our Familiar Friend, 1st ed.; Qian, X., Ed.; IntechOpen: Rijeka, Croatia, 306-324, 2012. DOI: http://dx.doi.org/10.5772/50103
[10] Yahi, D.; Ojo, N.A.; Mshelia, G.D.; "Influence of dexamethasone on some reproductive hormones and uterine progesterone receptor localization in pregnant Yankasa sheep in semiarid zones of Nigeria". J Vet Med., 2017(1): 9514861, 2017. DOI:
https://doi.org/10.1155/2017/9514861
[11] latif Al-Hussainy, A.D.; Khalaf, T.K.; "Effects of the prednisolone and hydrocortisone on the body weight of the pregnant rats and their embryo in the different stages of pregnancy". Al-Qadisiyah Med. J., 12(21):147-54, 2016. DOI:https://www.qmj.qu.edu.iq/index.php/QMJ/article/download/24/23
[12] Kurtoğlu, S.; Sarıcı, D.; Akın, M.A.; Daar, G.; Korkmaz, L.; Memur, Ş.; "Fetal adrenal suppression due to maternal corticosteroid use: case report". J Clin Res Pediatr Endocrinol, 3(3): 160, 2011. DOI: 10.4274/jcrpe.v3i3.31
[13] Priya, G.; Laway, B.A.; Ayyagari, M.; Gupta, M.; Bhat, G.H.; Dutta, D.; "The Glucocorticoid Taper: A Primer for the Clinicians". Indian J Endocrinol Metab, 28(4): 350-62, 2024. DOI: https://doi.org/10.4103/ijem.ijem_410_23
[14] Mateos, R.M.; Jiménez, G.; Álvarez-Gil C.; Visiedo, F.; Rivera-Rodríguez, F.; Santos-Rosendo, C.; Rodriguez-Pareja, A.; et al.; "Excess hydrocortisone hampers placental nutrient uptake disrupting cellular metabolism". Biomed Res. Int., 2018(1): 5106174, 2018. DOI: https://doi.org/10.1155/2018/5106174
[15] Thalluri, V.; Woodman, R.; Vollenhoven, B.; Tremellen, K.; Zander-Fox, D.; "Exposure to corticosteroids in the first trimester is associated with an increased risk of urogenital congenital anomalies". Hum. Reprod., 37(9): 2167-74, 2022. DOI: https://doi.org/10.1093/humrep/deac142
[16] Takahashi, M.; Ushijima, K.; Hayashi, Y.; Maekawa, T.; Ando, H.; Tsuruoka, S.I.; Fujimura, A.; et al.; "Dosing-time dependent effect of dexamethasone on bone density in rats". Life sci., 86(1-2): 24-9, 2010. DOI: https://doi.org/10.1016/j.lfs.2009.10.020
[17] Tomoko, F.; Matsue, H.; Mamoru, H.; "Functional effects of glucocorticoid exposure during fetal life". Prog Neuropsychopharmacol Biol Psychiatry, 17(2): 279-93, 1993. DOI: https://doi.org/10.1016/0278-5846(93)90048-W
[18] Ahmadabad, H.N.; Jafari, S.K.; Firizi, M.N.; Abbaspour, A.R.; Gharib, F.G.; Ghobadi, Y.; Gholizadeh, S.; et al.; "Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy". Clin Exp Reprod Med. , 43(1): 15, 2016. DOI: 10.5653/cerm.2016.43.1.15
[19] Lee, J.Y.; Park, S.; Kim, S.; Kim, M.; "Prenatal administration of dexamethasone during early pregnancy negatively affects placental development and function in mice". J Anim Sci., 90(13): 4846-56, 2012. DOI: https://doi.org/10.2527/jas.2012-5090
[20] Gunberg, D.L.; "Some effects of exogenous hydrocortisone on pregnancy in the rat". Anat Rec., 129(2): 133-53, 1957. DOI: https://doi.org/10.1002/ar.1091290202
[21] de Figueiredo Moraes, E.F.; Wanderley-Teixeira, V.; Teixeira A.A.C.; da Silva, W.E.; Batista A.P.C.; de Lemos, A.J.J.M.; "Effect of the treatment with dexamethasone, for 10 and 15 days, on the fertility in induced rats to polycystic ovaries, by constant illumination". Int. J. Morphol., 26(3):659-63, 2008. DOI: https://doi.org/10.4067/S071795022008000300024
[22] Wangui, N.U.; "Maternal Dexamethasone Use and Risk of Congenital Anomalies and Pre-term Births in Rats". Int. J. Appl. Sci. and Res., 4(5): 9, 2021.DOI: https://www.ijasr.org/paper/IJASR0042528.pdf
[23] Ahmed, A.A.; Barakat, N.T.; Ali, A.M.; Ismail, N.H.; Yaseen, N.Y.; Thaer, N.; Muttlak, F.A.; et al.; "Brain atrophy in Iraqi children associated with chromosome 6 abnormality". Al-Nahrain J. Sci, 17(4):180-5, 2014. DOI: 10.22401/JNUS.17.4.24
[24] Kemp, M.W.; Newnham, J.P.; Challis, J.; Jobe, A.H.; Stock, S.; "The clinical use of corticosteroids in pregnancy". Hum Reprod Update, 22(2): 240-59, 2016. DOI: https://doi.org/10.1093/humupd/dmv047
[25] Agnew, E.J.; Ivy, J.R.; Stock, S.J.; Chapman, K.E.; "Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation". J Mol Endocrinol., 61(1): R61-R73, 2018. DOI: https://doi.org/10.1530/JME-18-0077
[26] Cella, E.C.; Conte, J.; Stolte, R.C.; Lorenzon, F.; Gregorio, T.; Simas, B.B.; Rafacho, A.; et al.; "Gestational exposure to excessive levels of dexamethasone impairs maternal care and impacts on the offspring's survival in rats". Life Sci., 264: 118599, 2021. DOI: https://doi.org/10.1016/j.lfs.2020.118599
[27] Selvido, D.I.; Bhattarai, B.P.; Niyomtham, N.; Riddhabhaya, A.; Vongsawan, K.; Pairuchvej, V.; Wongsirichat, N.; et al.; "Review of dexamethasone administration for management of complications in postoperative third molar surgery". J Korean Assoc Oral Maxillofac Surg., 47(5): 341-50, 2021.DOI: https://doi.org/10.5125/jkaoms.2021.47.5.341
[28] Xiao, H.; He, B.; Liu, H.; Chen, Y.; Xiao, D.; Wang, H.; "Dexamethasone exposure during pregnancy triggers metabolic syndrome in offspring via epigenetic alteration of IGF1". Cell Commun Signal., 22(1): 62, 2024. DOI: https://doi.org/10.1186/s12964-024-01472-6
[29] Kwack, M.H.; Ben Hamida, O.; Kim, M.K.; Kim, J.C.; Sung, Y.K.; "Dexamethasone, a synthetic glucocorticoid, induces the activity of androgen receptor in human dermal papilla cells". Skin Pharmacol Physiol., 35(5): 299-304, 2022. DOI: https://doi.org/10.1159/000525067.
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