HSPC117 deficiency in cloned embryos causes placental abnormality and fetal death

Journal Article · Fri Jul 02 00:00:00 EDT 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2010.05.105· OSTI ID:22202669

Wang, Yingying ^[1]; Hai, Tang; Liu, Zichuan; Zhou, Shuya; Lv, Zhuo ^[2]; Ding, Chenhui; Liu, Lei ^[2]; Niu, Yuyu ^[1]; Zhao, Xiaoyang; Tong, Man ^[2]; Wang, Liu ^[2]; Jouneau, Alice ^[3]; Zhang, Xun ^[4]; Ji, Weizhi ^[1]; Zhou, Qi ^[2]

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1. Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China)
2. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China)
3. INRA, UMR 1198, ENVA, CNRS, FRE 2857, Biologie du Developpement et Reproduction, Jouy en Josas F-78350 (France)
4. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States)

Somatic cell nuclear transfer (SCNT) has been successfully used in many species to produce live cloned offspring, albeit with low efficiency. The low frequency of successful development has usually been ascribed to incomplete or inappropriate reprogramming of the transferred nuclear genome. Elucidating the genetic differences between normal fertilized and cloned embryos is key to understand the low efficiency of SCNT. Here, we show that expression of HSPC117, which encodes a hypothetical protein of unknown function, was absent or very low in cloned mouse blastocysts. To investigate the role of HSPC117 in embryo development, we knocked-down this gene in normal fertilized embryos using RNA interference. We assessed the post-implantation survival of HSPC117 knock-down embryos at 3 stages: E9 (prior to placenta formation); E12 (after the placenta was fully functional) and E19 (post-natal). Our results show that, although siRNA-treated in vivo fertilized/produced (IVP) embryos could develop to the blastocyst stage and implanted without any difference from control embryos, the knock-down embryos showed substantial fetal death, accompanied by placental blood clotting, at E12. Furthermore, comparison of HSPC117 expression in placentas of nuclear transfer (NT), intracytoplasmic sperm injection (ICSI) and IVP embryos confirmed that HSPC117 deficiency correlates well with failures in embryo development: all NT embryos with a fetus, as well as IVP and ICSI embryos, had normal placental HSPC117 expression while those NT embryos showing reduced or no expression of HSPC117 failed to form a fetus. In conclusion, we show that HSPC117 is an important gene for post-implantation development of embryos, and that HSPC117 deficiency leads to fetal abnormalities after implantation, especially following placental formation. We suggest that defects in HSPC117 expression may be an important contributing factor to loss of cloned NT embryos in vivo.

• OSTI ID: 22202669
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 397, Issue 3; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLOOD COAGULATION
DEATH
EMBRYOS
FETUSES
GENES
IN VIVO
MICE
PLACENTA
PROTEINS
RNA
SOMATIC CELLS
SPERMATOZOA