Production of offspring from azoospermic mice with meiotic failure: Precise biparental meiosis within halved oocytes

While the large volume of mammalian oocytes is necessary for embryo development, it can lead to error-prone chromosomal segregation during meiosis. Consequently, a smaller ooplasm might assure better chromosomal integrity of oocytes and embryos, but there is no evidence to support this hypothesis. Here, we show that reducing the ooplasm is 38 beneficial for assisted fertilization using primary spermatocytes, involving 39 synchronous biparental meiosis within oocytes. High-resolution live-imaging analysis revealed that erroneous chromosome segregation occurred in most (90%) spermatocyte-injected oocytes of normal size, but could be ameliorated to 40% in halved oocytes. The birth rate improved remarkably from 1% to 19% (P < 0.0001). Importantly, this technique enabled the production of offspring from azoospermic mice with spermatocyte arrest caused by STX2 deficiency, an azoospermia factor also found in humans. Thus, reduced ooplasmic volume can indeed correct the lethal meiotic errors and might help rescue cases of untreatable human azoospermia with spermatocyte arrest.