Shedding light on recruitment and differentiation of human theca interna cells

The transplantable engineered ovary is a promising approach to restore fertility in women and prepubertal girls at high risk of metastatic cancers. It is essentially a 3D matrix encapsulating isolated preantral follicles and ovarian cells. These cells are responsible for extracellular matrix and bioactive factor synthesis, as well as vascularization, and some will be recruited to differentiate into theca cells (TCs). Although TCs play a pivotal role in follicle development and steroid production, there is not much information on their recruitment and differentiation in human ovaries. Studies in animal models suggest two hypotheses on the origin of TCs: (i) a subpopulation of precursor TCs or (ii) all stromal cells are able to differentiate into TCs. To shed light on TC populations and their origin in the human ovary, we first investigated their steroidogenic pathway. We then assessed the presence of a subpopulation of precursor TCs in human fetal, prepubertal, reproductive-age and postmenopausal ovaries. While we could not identify them, we demonstrated that TCs could differentiate in vitro from stromal cells isolated from human postmenopausal ovarian cortex.