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

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REGULAR ARTICLE

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 Zhu & Qi Zhou & Jiahao Sha

Received: 3 January 2013 / Accepted: 2 September 2013 / Published online: 9 October 2013 # Springer-Verlag Berlin Heidelberg 2013

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

Yan Zeng and Zhuo Lv contributed equally to the work. This study was supported by grants from the Major State Basic Research Development Program of China (973 Program; no. 2012CB944902) and from the National Science Foundation of China (no. 31271604). Y. Zeng : L. Gu : Z. Zhou : H. Zhu (*) : J. Sha State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China e-mail: [email protected] Z. Lv : L. Wang : Q. Zhou (*) State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China e-mail: [email protected]

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)

Introduction Assisted reproductive technologies (ARTs) have been widely used in the treatment of human infertility. However, some processes involved in ART-mediated conception are markedly different from those in spontaneous conception, such as ovarian hyperstimulation and exposure of the embryo to tissue culture medium. Both clinical investigations and animal studies have indicated an increased inc