Effects of electromagnetic pulse on polydactyly of mouse fetusesby Ming-Juan Yang, Jun-Ye Liu, Ya-Feng Wang, Hai-yang Lang, Xia Miao, Li-Yan Zhang, Li-Hua Zeng, Guo-Zhen Guo

Theriogenology

About

Year
2013
DOI
10.1016/j.theriogenology.2013.03.004
Subject
Equine / Food Animals / Small Animals / Animal Science and Zoology

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Article history:

Received 6 July 2012

Received in revised form 18 March 2013

Accepted 18 March 2013

Keywords:

Electromagnetic pulse

Polydactyly

EMP signals, including strong electrical field apparatuses, such as high-pressure gas switches and Tesla transformer generators under certain occupational conditions. In addition, EMPs are used extensively in medical, security whole-body exposure (including exposure of the head) to 100 kV/m [4]. However, the International Commission on

Non-Ionizing Radiation Protection reference level for occupational exposure to electric fields that vary over time is 137 kV/m [5].

There is increasing interest in the link between EMR and human health [6,7]. Many researchers have suggested a link between EMR and various adverse effects on the * Corresponding authors. Tel.:þ86 29 84774873; fax:þ86 29 84774873.

E-mail addresses: lzwei1998@gmail.com (L.-H. Zeng), guozhen@ fmmu.edu.cn (G.-Z. Guo).

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Theriogenology 80 (2013) 18–231. Introduction

Modern technology has caused both the types and intensities of electromagnetic radiation (EMR) to increase rapidly. Every day, humans are exposed to various artificial sources of EMR. An electromagnetic pulse (EMP) is a highenergy electromagnetic wave with an extremely fast rising time and a broad bandwidth [1]. There are many sources of screening, and military applications [2,3]. The distinguishing properties of EMP have raised concerns regarding their biological effects and possible health hazards to humans, especially to some workers and researchers who are regularly exposed. Different countries and associations have issued different recommendations regarding reasonable limits to exposure. For example, in occupational cases, the Institute of Electrical and Electronics Engineers limitsFibroblast growth factor 4 (Fgf4)

Sonic hedgehog (Shh)

Kruppel family member 3 (Gli3)

Programmed cell death0093-691X/$ – see front matter  2013 Elsevier Inc http://dx.doi.org/10.1016/j.theriogenology.2013.03.0There is an increasing public concern regarding potential health impacts from electromagnetic radiation exposure. Embryonic development is sensitive to the external environment, and limb development is vital for life quality. To determine the effects of electromagnetic pulse (EMP) on polydactyly of mouse fetuses, pregnant mice were shamexposed or exposed to EMP (400 kV/m with 400 pulses) from Days 7 to 10 of pregnancy (Day 0 ¼ day of detection of vaginal plug). As a positive control, mice were treated with 5bromodeoxyuridine on Days 9 and 10. On Days 11 or 18, the fetuses were isolated.

Compared with the sham-exposed group, the group exposed to EMP had increased rates of polydactyly fetuses (5.1% vs. 0.6%, P < 0.05) and abnormal gene expression (22.2% vs. 2.8%,

P < 0.05). Ectopic expression of Fgf4 was detected in the apical ectodermal ridge, whereas overexpression and ectopic expression of Shh were detected in the zone of polarizing activity of limbs in the EMP-exposed group and in the positive control group. However, expression of Gli3 decreased in mesenchyme cells in those two groups. The percentages of programmed cell death of limbs in EMP-exposed and positive control group were decreased (3.57% and 2.94%, respectively, P < 0.05, compared with 7.76% in sham-exposed group). In conclusion, polydactyly induced by EMP was accompanied by abnormal expression of the above-mentioned genes and decreased percentage of programmed cell death during limb development.  2013 Elsevier Inc. All rights reserved.a r t i c l e i n f o a b s t r a c tEffects of electromagnetic pulse on

Ming-Juan Yang, Jun-Ye Liu, Ya-Feng Wang, H

Li-Hua Zeng*, Guo-Zhen Guo*

Department of Radiation Medicine and the Ministry of Education Key Lab of H

Health, Fourth Military Medical University, Xi’an, Shaanxi, China journal homepage:. All rights reserved. 04lydactyly of mouse fetuses yang Lang, Xia Miao, Li-Yan Zhang,

Assessment and Control in Special Operational Environment, School of Public ology . ther io journal .com

M.-J. Yang et al. / Theriogenology 80 (2013) 18–23 19nervous, endocrine, cardiovascular, and reproductive systems [8–11]. Some reports have also described teratogenicity, including polydactyly, when pregnant animals were exposed to EMR [12]. However, the specific mechanism underlying EMR-induced polydactyly has not been investigated. In the present study, pregnantmicewere used as a model to explore mechanisms of EMP-induced polydactyly. In this study, pregnant mice were exposed to EMP during the period of organogenesis, which is highly sensitive to teratogens [13].

Developmental systems of vertebrate limbs are accurately controlled by complex cellular and molecular mechanisms, depending on reciprocal interactions between the two signaling centers, namely the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). In these two centers, sonic hedgehog (SHH) and fibroblast growth factors (FGFs), respectively, are the key signaling molecules [14].

It is well established that Shh is associated with patterning of the anterior-posterior (A-P) axis and that it mediates the activity of the ZPA. It is also necessary for continuous limb growth. Interactions of Shh with AER help to establish all three of the limb axes (proximal-distal axis, anterior-posterior axis, and dorsal-ventral axis). The sonic hedgehog–Patched–Gli (Shh-Ptch-Gli) pathwaybeginswith the secreted protein Shh, which initiates a chain of events in target cells that leads to the activation and repression of target genes by transcription factors in the Gli family [15].

Although Gli1 and Gli2 are apparently indispensable during limb development, Kruppel family member 3 (Gli3) is especially crucial because all Gli3-associated human congenital diseases comprise limb malformations. Shh downregulates Gli3 expression in mesenchymal cells of the developing limb bud [16].

Proximal-distal limb outgrowth is controlled by the AER that expresses members of the FGF family. Experiments on chicks suggested that Shh expression in the ZPA is maintained by fibroblast growth factor 4 (Fgf4) expression in the