In mammals, ovaries contain a definite number of follicles, each containing a germ cell, the oocyte. The production of fertilizable ovocytes involves complex molecular, cellular, paracrine and endocrine mechanisms and requires a growth phase where RNAs, proteins and organelles accumulate. A ~300-fold increase in oocyte volume is observed during that period in the mouse. Throughout folliculogenesis, a large majority of ovarian follicles is eliminated by the process of follicular atresia, resulting in the death of the oocyte and companion granulosa cells. As oocytes are non-renewable, their progressive exhaustion eventually leads to ovarian senescence.
During folliculogenesis, oocyte growth is accompanied by a dramatic increase in gene transcription, a necessary step for the synthesis and storage of proteins ensuring oocyte growth and dialogue with companion granulosa cells in addition to fertilization and embryo development. Limited data is available regarding the transcriptional machinery and its regulation during oocyte growth and development. We used oocyte specific gene inactivation to study the interplay between pre-mRNA processing and maintenance of genomic integrity in female germ cells. We have generated a novel mouse mutant of premature ovarian insufficiency (POI) displaying complete elimination of early growing oocytes and sterility. This model represents a unique tool to identify the pathways involved in oocyte death. Moreover, the mutant female mice exhibit patterns of sexual cyclicity despite the absence of terminal folliculogenesis. This challenges, in the case of premature ovarian insufficiency, the current dogma whereby sexual cyclicity is tightly dependent upon oocyte endowment and pace of folliculogenesis. This work was supported by the ANR EARLYFOLL and is performed in collaboration with the team “Physiology of Gonadotrope Axis” from the university Paris-Diderot.
We are also characterizing ribosome biogenesis during folliculogenesis and analysing the impact of perturbations of this process on growth and acquisition of developmental competences of mouse oocytes.