Role Of S100 Calcium Binding Protein A8 During Mouse Primordial Folliculogenesis

In mammal ovaries, follicles is the basic structure and functional unit of the gland. As the first developmental stage of a follicle, primordial follicle is the only source of mature oocytes for fertilization. Hence, the follicle number of a primordial follicle pool determines a female animal’s life long reproductive capability. The primordial follicle is composed by two cell members, the oocyte and the pre-granulosa cells surrounding the oocyte. However, it is unclear who initiates the process to organize the two distinct types of cells.By assistant with a series of in vitro experiments, this study used 19.0 day post coitum (dpc) fetal mouse ovary as experimental material to examine the interaction between the pre-granulosa cells and the oocytes, which aimed at exploring the uncovered mechanism regulating primordial follicle assembly. First, as proved by a follicle in vitro reconstruction system, dispersed ovarian cells from 19.0 dpc fetal ovary were able to reassemble into follicle-like structure even though physical distance existed among the cells, implying that either oocytes or ovarian somatic cells (OSCs) were motile. Then, in a transwell assay, purified 19.0 dpc fetal OSCs showed significant chemotactic response to fetal bovine serum than the oocytes. And a similar response of the OSCs can be induced by the oocytes. This result indicated that oocyte might be capable of recruiting OSCs. Inspiringly, S100A8, a multi-function chemokine, was found to be expressed mainly in oocytes within the cysts/plasmodia perinatally. On the one hand, as demonstrated by the transwell assay, the addition of S100A8 not only significantly promoted the number of total migrating OSCs, but also the OSCs expressing FOXL2, a proved pre-granulosa cell bio-marker, as well as its ration of total migrated cell. On the other hand, S100A8 specific antibody can dosage-dependently inhibit the formation of follicle-like reconstruction cell mass in vitro. Meanwhile, the primordial follicle formation was reduced when S100α8-specific siRNA was applied to in vitro cultured 17.5 dpc ovaries. Collectively, S100A8 might be an oocytes origin chemokine that attracts OSCs to form the primordial follicles.In conclusion, S100A8 is an oocyte-expressed chemotaxin which functions by directing OSC migration during primordial follicle formation. The S100A8 protein itself, along with S100A8-related processes may provide greater understanding about the cell behavior during primordial follicle assembly. However, the exact function of S100A8 on primordial follicle formation in vivo needs further study.