Autophagic activity as an indicator for selecting good quality embryos

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Autophagic activity as an indicator for selecting good quality embryos Satoshi Tsukamoto

Received: 30 June 2014 / Accepted: 9 October 2014 Ó Japan Society for Reproductive Medicine 2014

Abstract Is it possible to predict the quality of embryos that appear to be morphologically identical when viewed under a microscope? Thirty-five years have passed since the world’s first human birth from in vitro fertilization. While the dissemination of assisted reproduction technologies during this time has been remarkable, the evaluation of embryo quality in both humans and mice currently relies entirely on morphological observation. More efficient infertility treatments will likely be possible if high-quality embryos can be selected by screening. To develop a novel quality evaluation method that does not rely on morphology, we focused on autophagy, one of the molecular mechanisms essential for the early embryonic development. Autophagy is a massive cytoplasmic degradation pathway mediated by the lysosome. Our previous studies have demonstrated that fertilization-induced autophagy is essential for preimplantation embryonic development. This autophagy is thought to supply the nutrients and amino acids necessary for maintaining subsequent embryo development, through the bulk degradation of maternal cytoplasmic factors that are accumulated during oogenesis. Here, we briefly summarize autophagy and its physiological function, and describe a recently developed method for using autophagic activity as an indicator to predict embryo quality. Keywords Assisted reproductive technologies  Autophagy  Embryo quality  Fertilization  GFP-LC3  Mice

S. Tsukamoto (&) Laboratory Animal and Genome Sciences Section, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan e-mail: [email protected]

Introduction The world’s first child conceived through in vitro fertilization (IVF), generally referred to as a test tube baby, was born in 1978 in the United Kingdom [1]. In Japan, currently one out of every 40 individuals is born through assisted reproductive technologies (ART) such as IVF; however, ART results in live birth in only 10.7 % of cases [2]. Among the various reasons for such a low rate, reduced embryo quality due to maternal aging has become a major causal factor. Moreover, even if multiple embryos are obtained through IVF, only one embryo can be transferred into the uterus of the mother, due to the higher risk of multiple pregnancy when multiple embryos are transferred [3, 4]. It is important, therefore, to select the high-quality embryos for transfer from among those collected. Generally, a grading method is used that is based on morphological observation of the nucleus and cytoplasm of the embryos [5]. In some cases, however, embryos given a low grade grow normally following implantation. This can also be observed with mouse embryos. As such, it is difficult to conclude that morphological grade correlates with embryo viability. It appears important then to supplement conventiona