Abstract
Human ovarian folliculogenesis is a highly regulated and complex process. Characterization of follicular cell signatures during this dynamic process is important to understand follicle fate (to grow, become dominant, or undergo atresia). The transcriptional signature of human oocytes and granulosa cells (GCs) in early-growing and ovulatory follicles have been previously described; however, that of oocytes with surrounding GCs in small antral follicles have not been studied yet. Here, we have generated a unique dataset of single-cell transcriptomics (SmartSeq2) consisting of the oocyte with surrounding GCs from several individual (non-dominant) small antral follicles isolated from adult human ovaries. We have identified two main types of (healthy) follicles, with a distinct oocyte and GC signature. Using the CellphoneDB algorithm, we then investigated the bi-directional ligand–receptor interactions regarding the transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP), wingless-type (MMTV)-integration site (WNT), NOTCH, and receptor tyrosine kinases (RTK) signaling pathways between oocyte and GCs within each antral follicle type. Our work not only revealed the diversity of small antral follicles, but also contributes to fill the gap in mapping the molecular landscape of human folliculogenesis and oogenesis.
Highlights
Human ovarian folliculogenesis represents one of the most complex biological processes within the body and protocols to recapitulate folliculogenesis in vitro in clinical settings are highly desirable for fertility preservation purposes [1,2]
The generation of primordial ovarian follicles, consisting of an oocyte arrested at the diplotene stage of meiotic prophase I surrounded by a single layer of flat granulosa cells (GCs) occurs before birth [4,5]
From the four small antral follicles that we examined, AF9.3b showed a small number of GCs expressing high levels of S100B and lower expression of GJA1, compared with the other three follicles (AF10.3, AF8.3, AF10.1a) (Figure 4E,F)
Summary
Human ovarian folliculogenesis represents one of the most complex biological processes within the body and protocols to recapitulate folliculogenesis in vitro in clinical settings are highly desirable for fertility preservation purposes [1,2]. Its complexity is reflected in the balance between growth and remodeling of the ovarian follicles, and on the high level of synchronization in the different follicular cell types within one follicle with the common goal of producing a competent mature oocyte [3]. The generation of primordial ovarian follicles, consisting of an oocyte arrested at the diplotene stage (dictyate) of meiotic prophase I surrounded by a single layer of flat (or squamous) granulosa cells (GCs) occurs before birth [4,5]. A pool of primordial follicles will become active, the layer of GCs surrounding the oocyte will change morphology from flat to cuboidal and the oocyte will start increasing in size. Factors that determine follicle fate (dominance or atresia) are still not well understood [7,11]
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