Human ovarian cell map from womb to menopause for data-driven development of folliculogenesis in vitro

Female fertility depends on ovaries that harbor the reserve of immature oocytes and produce hormones. Incontrast to men, fertility in women is limited ending in menopause.

The limiting role of oocytes is reflected by the diversity of experimental fertility treatment options being developed for women ranging from growing oocytes in vitro to transplantable ovarian constructs. None of the approaches has been successful.

The purpose of this ambitious project is to map human ovarian cell types from fetal development to menopause in order to enable data-driven reconstruction of folliculogenesis in the laboratory.

Using high-quality ovarian tissue and single-cell profiling techniques, we will delineate cell types and mechanism controlling germ line differentiation and development.

Infrastructure and methods are in place due to our work on adult ovariant tissue (Wagner et al. 2020 Nat Commns) and Sveafertil, a national fertility preservation project for girls that we have started.

Specifically, we will map ovarian cell types as a function of age; carry out deep RNA analysis of isolated follicles; isolate and culture key cell types; and use the data to recreate folliculogenesis in vitro. The applicants have expertise covering all aspects of the project.

The results could lead to a paradigm shift in assisted reproduction in addition to informing about mechanisms of ovarian senescence, molecular targets for contraception and giving models for assessing drug and chemical safety.