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There is no doubt that intracytoplasmic sperm injection (ICSI) has been a major breakthrough in treating male infertility, accounting for 70–80% of all the cycles performed worldwide. Surprisingly, there were very few animal studies conducted before the first babies were born, in part because of technical challenges that were experienced in most animal systems. Technological advancements were required to develop appropriate animal models for assessing the safety of ICSI. These studies identified many cytoskeletal changes that occurred in the oocyte cytoplasm after ICSI versus natural conception or even IVF, raising concerns about the long-term health of ICSI offspring. This chapter summarizes the animal models that have contributed to our understanding of the cellular and molecular aspects of ICSI, as well as providing models to investigate both the developmental origins of adult disease and transgenerational implications as they relate to ICSI.
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