Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Prenatal Stress Induces Skeletal Malformations in Mouse Embryos

  • Kim, Jongsoo (Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine) ;
  • Yun, Hyo Jung (Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine) ;
  • Lee, Ji-Yeon (Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine) ;
  • Kim, Myoung Hee (Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine)
  • Received : 2014.10.21
  • Accepted : 2014.12.05
  • Published : 2015.03.31
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Abstract

Dexamethasone, a synthetic glucocorticoid (GC), is clinically administered to woman at risk for premature labor to induce fetal lung maturation. However, exposure to repeated or excess GCs leads to intrauterine growth restriction (IUGR) and subsequently increases risk of psychiatric and cardio-metabolic diseases in later life through fetal programming mechanisms. GCs are key mediators of stress responses, therefore, maternal nutrient restriction or psychological stress during pregnancy also causes negative impacts on birth and neurodevelopment outcome of fetuses, and other congenital defects, such as craniofacial and skeletal abnormalities. In this study, to examine the effect of prenatal stress on fetal skeletal development, dexamethasone (1 mg/kg [DEX1] or 10 mg/kg [DEX10] maternal body weight per day) was administered intraperitoneally at gestational day 7.5~9.5 and the skeletons were prepared from embryos at day 18.5. Seven out of eighteen (39%) embryos treated with DEX10 showed axial skeletal abnormalities in either the T13 or L1 vertebrae. In addition, examination of the sternum revealed that xiphoid process, the protrusive triangular part of the lower end of the sternum, was bent more outward or inward in DEX group embryos. In conclusion, our findings suggest a possible link to the understanding of the effect of uterine environment to the fetal skeletal features.

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References

  1. Bale TL. Sex differences in prenatal epigenetic programming of stress pathways. Stress. 2011. 14: 348-356. https://doi.org/10.3109/10253890.2011.586447
  2. Canalis E. Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep. 2005. 3: 98-102. https://doi.org/10.1007/s11914-005-0017-7
  3. Choe HK, Son GH, Chung S, Kim M, Sun W, Kim H, Geum D, Kim K. Maternal stress retards fetal development in mice with transcriptome-wide impact on gene expression profiles of the limb. Stress. 2011. 14: 194-204. https://doi.org/10.3109/10253890.2010.529972
  4. Cuffe JSM, Dickinson H, Simmons DG, Moritz KM. Sex specific changes in placental growth and MAPK following short term maternal dexamethasone exposure in the mouse. Placenta. 2011. 32: 981-989. https://doi.org/10.1016/j.placenta.2011.09.009
  5. del Mar Lorente M, Marcos-Gutierrez C, Perez C, Schoorlemmer J, Ramirez A, Magin T, Vidal M. Loss- and gain-of-function mutations show a polycomb group function for Ring1A in mice. Development. 2000. 127: 5093-5100.
  6. Donet E, Bayo P, Calvo E, Labrie F, Perez P. Identification of novel glucocorticoid receptor-regulated genes involved in epidermal homeostasis and hair follicle differentiation. J Steroid Bioche Mol Biol. 2008. 108: 8-16. https://doi.org/10.1016/j.jsbmb.2007.05.033
  7. Eijken M, Koedam M, van Driel M, Buurman CJ, Pols HA, van Leeuwen JP. The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol Cell Endocrinol. 2006. 248: 87-93. https://doi.org/10.1016/j.mce.2005.11.034
  8. Faichney GJ, White GA. Effect of maternal nutritional status on fetal and placental growth and on fetal urea synthesis in sheep. Aus J Biol Sci. 1987. 40: 365-378. https://doi.org/10.1071/BI9870365
  9. Favier B, Dolle P. Developmental functions of mammalian Hox genes. Mol Hum Reprod. 1997. 3: 115-131. https://doi.org/10.1093/molehr/3.2.115
  10. Fokin AA, Steuerwald NM, Ahrens WA, Allen KE. Anatomical, histologic, and genetic characteristics of congenital chest wall deformities. Semin Thorac Cardiovasc Surg. 2009. 21: 44-57. https://doi.org/10.1053/j.semtcvs.2009.03.001
  11. Gale CR, Martyn CN, Kellingray S, Eastell R, Cooper C. Intrauterine programming of adult body composition. J Clin Endocrinol Metab. 2001. 86: 267-272.
  12. Garcia-Caceres C, Lagunas N, Calmarza-Font I, Azcoitia I, Diz-Chaves Y, Garcia-Segura LM, Baquedano E, Frago LM, Argente J, Chowen JA. Gender differences the long-term effects of chronic prenatal stress on the HPA axis and hypothalamic structure in rats. Psychoneuroendocrinology. 2010. 35: 1525-1535. https://doi.org/10.1016/j.psyneuen.2010.05.006
  13. Glover V, Hill J. Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: An evolutionary perspective. Physiol Behav. 2012. 106: 736-740. https://doi.org/10.1016/j.physbeh.2012.02.011
  14. Henneicke H, Gasparini SJ, Brennan-Speranza TC, Zhou H, Seibel MJ. Glucocorticoids and bone: local effects and systemic implications. Trends Endocrinol Metab. 2014. 25: 197-211. https://doi.org/10.1016/j.tem.2013.12.006
  15. Kim SH, Lee J-Y, Park SJ, Kim MH. Effects of dexamethasone on embryo development and Hox gene expression patterns in mice. J Exp Biomed Sci. 2011. 17: 231-238.
  16. Korakaki E, Damilakis J, Gourgiotis D, Katonis P, Aligizakis A, Yachnakis E, Stratakis J, Manoura A, Hatzidaki E, Saitakis E, Giannakopoulou C. Quantitative ultrasound measurements in premature infants at 1 year of age: the effects of antenatal administered corticosteroids. Calcif Tissue Int. 2011. 88: 215-222. https://doi.org/10.1007/s00223-010-9451-3
  17. Korakaki E, Gourgiotis D, Aligizakis A, Manoura A, Hatzidaki E, Giahnakis E, Marmarinos A, Kalmanti M, Giannakopoulou C. Levels of bone collagen markers in preterm infants: relation to antenatal glucocorticoid treatment. J Bone Miner Metab. 2007. 25: 172-178. https://doi.org/10.1007/s00774-006-0742-8
  18. Lee J-Y, Park SJ, Kim SH, Kim MH. Prenatal administration of dexamethasone during early pregnancy negatively affects placental development and function in mice. J Anim Sci. 2012. 90: 4846-4856. https://doi.org/10.2527/jas.2012-5090
  19. Lee YE, Byun SK, Shin S, Jang JY, Choi B-I, Park D, Jeon JH, Nahm S-S, Kang J-K, Hwang S-Y, Kim J-C, Kim Y-B. Effect of maternal restraint rtress on fetal development of ICR mice. Exp Anim. 2008. 57: 19-25. https://doi.org/10.1538/expanim.57.19
  20. Lorente M, Perez C, Sanchez C, Donohoe M, Shi Y, Vidal M. Homeotic transformations of the axial skeleton of YY1 mutant mice and genetic interaction with the Polycomb group gene Ring1/Ring1A. Mech Dev. 2006. 123: 312-320. https://doi.org/10.1016/j.mod.2006.02.003
  21. Lumey L. Compensatory placental growth after restricted maternal nutrition in early pregnancy. Placenta. 1998. 19: 105-111. https://doi.org/10.1016/S0143-4004(98)90105-9
  22. Mallo M, Vinagre T, Carapuco M. The road to the vertebral formula. Int J Dev Biol. 2009. 53: 1469-1481. https://doi.org/10.1387/ijdb.072276mm
  23. McCrabb GJ, Egan AR, Hosking BJ. Maternal undernutrition during mid-pregnancy in sheep: Variable effects on placental growth. J Agric Sci. 1992. 118: 127-132. https://doi.org/10.1017/S002185960006809X
  24. Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008. 28: 9055-9065. https://doi.org/10.1523/JNEUROSCI.1424-08.2008
  25. Newnham JP, Moss TJ. Antenatal glucocorticoids and growth:single versus multiple doses in animal and human studies. Semin Neonatol. 2001. 6: 285-292. https://doi.org/10.1053/siny.2001.0064
  26. O'Connell BA, Moritz KM, Roberts CT, Walker DW, Dickinson H. The placental response to excess maternal glucocorticoid exposure differs between the male and female conceptus in spiny mice. Biol Reprod. 2011. 85: 1040-1047. https://doi.org/10.1095/biolreprod.111.093369
  27. Robicsek F, Watts LT, Fokin AA. Surgical repair of pectus excavatum and carinatum. Semin Thorac Cardiovasc Surg. 2009. 21: 64-75. https://doi.org/10.1053/j.semtcvs.2009.03.002
  28. Sliwa E, Tatara MR, Nowakowski H, Pierzynowski SG, Studzinski T. Effect of maternal dexamethasone and alpha-ketoglutarate administration on skeletal development during the last three weeks of prenatal life in pigs. J Matern Fetal Neonatal Med. 2006. 19: 489-493. https://doi.org/10.1080/14767050600850381
  29. Sloboda D, Challis J, Moss T, Newnham J. Synthetic glucocorticoids:antenatal administration and long-term implications. Curr Pharm Des. 2005. 11: 1459-1472. https://doi.org/10.2174/1381612053507873
  30. Subramaniam N, Campion J, Rafter I, Okret S. Cross-talk between glucocorticoid and retinoic acid signals involving glucocorticoid receptor interaction with the homoeodomain protein Pbx1. Biochem J. 2003. 370: 1087-1095. https://doi.org/10.1042/bj20020471
  31. Swolin-Eide D, Dahlgren J, Nilsson C, Albertsson Wikland K, Holmang A, Ohlsson C. Affected skeletal growth but normal bone mineralization in rat offspring after prenatal dexamethasone exposure. J Endocrinol. 2002. 174: 411-418. https://doi.org/10.1677/joe.0.1740411
  32. Tegethoff M, Greene N, Olsen J, Meyer AH, Meinlschmidt G. Maternal psychosocial stress during pregnancy and placental weight: Evidence from a national cohort study. PLoS One. 2010. 5: e14478. https://doi.org/10.1371/journal.pone.0014478
  33. van Den Akker E, Fromental-Ramain C, de Graaff W, Le Mouellic H, Brulet P, Chambon P, Deschamps J. Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes. Development. 2001. 128: 1911-1921.
  34. Ward R. Pharmacologic enhancement of fetal lung maturation. Clin Perinatol. 1994. 21: 523-542. https://doi.org/10.1016/S0095-5108(18)30330-0
  35. Weinstein RS. Glucocorticoid-induced bone disease. New Eng J Med. 2011. 365: 62-70. https://doi.org/10.1056/NEJMcp1012926
  36. Wellik DM, Capecchi MR. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science. 2003. 301: 363-367. https://doi.org/10.1126/science.1085672
  37. Yun HJ, Lee J-Y, Kim J, Kim MH. Effect of prenatal dexamethasone on sex-specific changes in embryonic and placental growth. Biomed Sci Lett. 2014. 20: 43-47.