Developmental and functional evidence of nuclear immaturity in prepubertal oocytes

Background: The nuclear compartment has been proposed as responsible for the developmental arrest of prepubertal mouse oocytes while the studies on prepubertal sheep and cow oocyte model suggested the cytoplasm immaturity accounts for this failure. Methods: The apparent disagreement on the causes of developmental defects between these two species prompted us to study: (i) follicular and oocyte growth allometry in lambs, (ii) oocyte compartment (nucleus versus cytoplasm) responsible for developmental failure by nucleus exchange between lamb and adult sheep oocytes, (iii) nucleolar features of prepubertal oocytes by ultrastructural observation and (iv) in vivo developmental survey of prepubertally derived embryos. Results: The oocyte growth inside the follicle is asynchronous during prepuberty. The nuclear transfer revealed that the lamb nucleus was responsible for developmental failure. Immature fibrillogranular structure of the nucleolus has been revealed in small lamb oocytes and also in a few adult-size lamb oocytes. Studies in vivo revealed a high occurrence of developmental arrest of prepubertal derived fetuses, which we have attributed to the low genome-wide methylation detected in prepubertal oocytes. Conclusions: Our studies have indicated incomplete nuclear maturation of prepubertal gamete. The implication of this finding suggests caution when the strategy of rescue of prepubertal oocytes for assisted fertilization is considered such as in the case of therapeutic treatment which precludes the maintenance of fertility of sexually immature patients