Advertisement

Cell and Tissue Research

, Volume 354, Issue 3, pp 729–741 | Cite as

Preimplantation genetic diagnosis (PGD) influences adrenal development and response to cold stress in resulting mice

  • Yan Zeng
  • Zhuo Lv
  • Leilei Gu
  • Liu Wang
  • Zuomin Zhou
  • Hui ZhuEmail author
  • Qi ZhouEmail author
  • Jiahao Sha
Regular Article

Abstract

Preimplantation genetic diagnosis (PGD) has gained widespread application in clinical medicine and hence the health of PGD offspring needs to be systematically assessed. Given the critical role of the stress response in growth and health, assessments of the development and function of the stress system might help to clarify the health outcomes of PGD. In this study, we constructed a PGD-conceived mouse model and used naturally conceived mice as controls; we used this model to evaluate the potential effect of PGD procedures on the stress system of the offspring. Serum and tissues of stress organs, namely the hypothalamus, locus coeruleus and adrenal gland, were collected from 5-week-old mice in the basal state or after cold stress. The serum levels of stress-related hormones and the structural and functional indices of the stress organs were then examined. In the basal state, ultrastructural abnormalities and low expression of genes involved in steroid hormone synthesis were found in the adrenals of the PGD mice, which had low corticosterone and high epinephrine levels compared with those of control mice. After acute cold stress, the PGD mice continued to show structural and glucocorticoid secretion abnormalities resulting in a late response to the environmental change. Thus, our study indicates that PGD manipulations affect adrenal development, result in structural and functional abnormalities of the adrenals in the offspring and influence their reactivity and adaptability to cold stress.

Keywords

Preimplantation genetic diagnosis (PGD) Assisted reproduction technology (ART) Adrenal gland Corticosterone Cold stress Mouse (ICR) 

Notes

Acknowledgments

We thank Prof. Ming Xiao for his technical support during the brain morphological analysis.

References

  1. Bernuci MP, Szawka RE, Helena CVV, Leite CM, Lara HE, Anselmo-Franci JA (2008) Locus coeruleus mediates cold stress-induced polycystic ovary in rats. Endocrinology 149:2907–2916PubMedCrossRefGoogle Scholar
  2. Bielohuby M, Herbach N, Wanke R, Maser-Gluth C, Beuschlein F, Wolf E, Hoeflich A (2007) Growth analysis of the mouse adrenal gland from weaning to adulthood: time- and gender-dependent alterations of cell size and number in the cortical compartment. Am J Physiol Endocrinol Metab 293:E139–E146PubMedCrossRefGoogle Scholar
  3. Bland ML, Desclozeaux M, Ingraham HA (2003) Tissue growth and remodeling of the embryonic and adult adrenal gland. Ann N Y Acad Sci 995:59–72PubMedCrossRefGoogle Scholar
  4. Chrousos GP (2009) Stress and disorders of the stress system. Nat Rev Endocrinol 5:374–381PubMedCrossRefGoogle Scholar
  5. Crivellato E, Nico B, Perissin L, Ribatti D (2003) Ultrastructure morphology of adrenal chromaffin cells indicative of a process of piecemeal degranulation. Anat Rec A Discov Mol Cell Evol Biol 270:103–108PubMedCrossRefGoogle Scholar
  6. Crivellato E, Belloni A, Nico B, Nussdorfer GG, Ribatti D (2004) Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion. Anat Rec A Discov Mol Cell Evol Biol 277:204–208PubMedCrossRefGoogle Scholar
  7. de Mouzon J, Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, Kupka M, Nygren KG, Andersen AN (2012) Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE. Hum Reprod 27:954–966PubMedCrossRefGoogle Scholar
  8. Desmyttere S, Bonduelle M, Nekkebroeck J, Roelants M, Liebaers I, Schepper JD (2009) Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening. Early Hum Dev 85:755–759PubMedCrossRefGoogle Scholar
  9. Ecker DJ, Stein P, Xu Z, Williams CJ, Kopf GS, Bilker WB, Abel T, Schultz RM (2004) Long-term effects of culture of preimplantation mouse embryos on behavior. Proc Natl Acad Sci U S A 101:595–1600CrossRefGoogle Scholar
  10. El-Maghraby M, Lever JD (1980) Typification and differentiation of medullary cells in the developing rat adrenal. A histochemical and electron microscopic study. J Anat 131:103–120PubMedGoogle Scholar
  11. Ferraz-de-Souza B, Achermann JC (2008) Disorders of adrenal development. Endocr Dev 13:19–32PubMedCrossRefGoogle Scholar
  12. Handyside AH, Kontogianni EH, Hardy K, Winston RM (1990) Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344:768–770PubMedCrossRefGoogle Scholar
  13. Hardy K, Martin KL, Leese HJ, Winston RM, Handyside AH (1990) Human preimplantation development in vitro is not adversely affected by biopsy at the 8-cell stage. Hum Reprod 5:708–714PubMedGoogle Scholar
  14. Hu DG, Webb G, Hussey N (2004) Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization. Mol Hum Reprod 10:283–289PubMedCrossRefGoogle Scholar
  15. Hu DG, Guan XY, Hussey N (2007) Gender determination and detection of aneuploidy in single cells using DNA array-based comparative genomic hybridization. Methods Mol Med 132:135–151PubMedCrossRefGoogle Scholar
  16. Klein SC, Peterson ME (2010) Canine hypoadrenocorticism: part I. Can Vet J 51:63–69PubMedGoogle Scholar
  17. Kovacs KJ (1998) c-Fos as a transcription factor: a stressful (re)view from a functional map. Neurochem Int 33:287–297PubMedCrossRefGoogle Scholar
  18. Kvetnansky R, Sabban EL, Palkovits M (2009) Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 89:535–606PubMedCrossRefGoogle Scholar
  19. Kyrou I, Tsigos C (2009) Stress hormones: physiological stress and regulation of metabolism. Curr Opin Pharmacol 9:787–793PubMedCrossRefGoogle Scholar
  20. Maher ER (2005) Imprinting and assisted reproductive technology. Hum Mol Genet 14:R133–R138PubMedCrossRefGoogle Scholar
  21. McDonald SD, Murphy K, Beyene J, Ohlsson A (2005) Perinatal outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. J Obstet Gynaecol Can 27:449–459PubMedGoogle Scholar
  22. Middelburg KJ, Heide M van der, Houtzager B, Jongbloed-Pereboom M, Fidler V, Bos AF, Kok J, Hadders-Algra M, PGS-Follow-up Study Group (2011) Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial. Fertil Steril 96:165–169PubMedCrossRefGoogle Scholar
  23. Miles HL, Hofman PL, Peek J, Harris M, Wilson D, Robinson EM, Gluckman PD, Cutfield WS (2007) In vitro fertilization improves childhood growth and metabolism. J Clin Endocrinol Metab 92:3441–3445PubMedCrossRefGoogle Scholar
  24. Miller WL (1995) Mitochondrial specificity of the early steps in steroidogenesis. J Steroid Biochem Mol Biol 55:607–616PubMedCrossRefGoogle Scholar
  25. Miller WL (2011) Role of mitochondria in steroidogenesis. Endocr Dev 20:1–19PubMedGoogle Scholar
  26. Provost PR (2005) Genes involved in the adrenal pathway of glucocorticoid synthesis are transiently expressed in the developing lung. Endocrinology 146:2239–2245PubMedCrossRefGoogle Scholar
  27. Sakka SD, Loutradis D, Kanaka-Gantenbein C, Margeli A, Papastamataki M, Papassotiriou I, Chrousos GP (2010) Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization. Fertil Steril 94:1693–1699PubMedCrossRefGoogle Scholar
  28. Sermon K, Van Steirteghem A, Liebaers I (2004) Preimplantation genetic diagnosis. Lancet 363:1633–1641PubMedCrossRefGoogle Scholar
  29. Watkins AJ, Platt D, Papenbrock T, Wilkins A, Eckert JJ, Kwong WY, Osmond C, Hanson M, Fleming TP (2007) Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure. Proc Natl Acad Sci U S A 104:5449–5454PubMedCrossRefGoogle Scholar
  30. Wells D, Levy B (2003) Cytogenetics in reproductive medicine: the contribution of comparative genomic hybridization (CGH). Bioessays 25:289–300PubMedCrossRefGoogle Scholar
  31. Wilson CL, Fisher JR, Hammarberg K, Amor DJ, Halliday JL (2011) Looking downstream: a review of the literature on physical and psychosocial health outcomes in adolescents and young adults who were conceived by ART. Hum Reprod 26:1209–1219PubMedCrossRefGoogle Scholar
  32. Wilton L (2002) Preimplantation genetic diagnosis for aneuploidy screening in early human embryos: a review. Prenat Diagn 22:512–518PubMedCrossRefGoogle Scholar
  33. Winston RM, Hardy K (2002) Are we ignoring potential dangers of in vitro fertilization and related treatments? Nat Cell Biol 4(s1):s14–s18PubMedCrossRefGoogle Scholar
  34. Yu Y, Wu J, Fan Y, Lv Z, Guo X, Zhao C, Zhou R, Zhang Z, Wang F, Xiao M, Chen L, Zhu H, Chen W, Lin M, Liu J, Zhou Z, Wang L, Huo R, Zhou Q, Sha J (2009) Evaluation of blastomere biopsy using a mouse model indicates the potential high risk of neurodegenerative disorders in the offspring. Mol Cell Proteomics 8:1490–1500PubMedCrossRefGoogle Scholar
  35. Ziegler MG, Elayan H, Milic M, Sun P, Gharaiben M (2012) Epinephrine and the metabolic syndrome. Curr Hypertens Rep 14:1–7PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.State Key Laboratory of Reproductive Medicine, Department of Histology and EmbryologyNanjing Medical UniversityNanjingChina
  2. 2.State Key Laboratory of Reproductive Biology, Institute of ZoologyChinese Academy of ScienceBeijingChina

Personalised recommendations