TOP6BL, also known as C11orf80, is an essential partner of SPO11 protein. It plays a crucial role in the meiotic recombination pathway, where meiotic programmed DNA double-strand breaks (DSBs) are formed. This process is vital for sexual reproduction and fertility as it ensures faithful chromosome segregation and gamete generation [1,2,3].

In a study of four infertile siblings from a consanguineous marriage, an autosomal recessive mutation in TOP6BL was found co-segregating with infertility. In a male patient, this led to failure in programmed meiotic DSB formation and meiotic arrest prior to the pachytene stage of prophase I. Mouse models carrying similar mutations recapitulated the spermatogenic abnormalities seen in the patient. In female patients, observations in mice showed that meiotic programmed DSBs failed to form in mutant oocytes, resulting in oocyte maturation failure due to absence of meiotic recombination [1]. Also, bi-allelic deleterious mutations in TOP6BL were identified in women with recurrent androgenetic complete hydatidiform moles, suggesting its role in preventing such abnormal pregnancies [4].

In conclusion, TOP6BL is essential for meiotic DSB formation, which is crucial for normal sexual reproduction and fertility. Mouse models with TOP6BL mutations have been valuable in revealing its role in spermatogenic and oogenic processes, as well as in understanding the mechanisms behind certain infertility-related conditions like non-obstructive azoospermia, unexplained female infertility, and recurrent androgenetic complete hydatidiform moles [1,4].