Birth of mice from meiotically arrested spermatocytes following biparental meiosis in halved oocytes

Abstract

Microinjection of spermatozoa or spermatids into oocytes is a major choice for infertility treatment. However, the use of premeiotic spermatocytes has never been considered because of its technical problems. Here, we show that the efficiency of spermatocyte injection in mice can be improved greatly by reducing the size of the recipient oocytes. Live imaging showed that the underlying mechanism involves reduced premature separation of the spermatocyte's meiotic chromosomes, which produced much greater (19% vs. 1%) birth rates in smaller oocytes. Application of this technique to spermatocyte arrest caused by STX2 deficiency, an azoospermia factor also found in humans, resulted in the production of live offspring. Thus, the microinjection of primary spermatocytes into oocytes may be a potential treatment for overcoming a form of nonobstructive azoospermia caused by meiotic failure.

The large cytoplasmic volume of oocyte

“…In human oocytes, chromosomal misalignment due to unstable spindle bipolarity does not block anaphase onset through the spindle checkpoint [ 99 ]. A recent study showed that the efficiency of spermatocyte injection in mice could be greatly improved by reducing the size of recipient oocytes [ 100 ]. In this study, spermatocyte chromosomes, which might be intrinsically more error-prone, were dramatically rescued from segregation error by reducing the cytoplasm.…”

Working in close quarters: biparental meiosis in the oocyte

“…A study by Ogonuki et al ( 2022 ) of EMBO Reports deals with a different in vitro fertilization method in mouse oocytes: injection of diploid sperm nuclei before they undergo the first meiotic division, into equally diploid, GV‐stage oocytes. The logic behind this approach is that the oocyte cytoplasm should be able to support the meiotic divisions not only of female, but also of male chromosomes, should they be present (i.e., biparental meiosis).…”