Diseases of the Reproductive System
(T212) CONSEQUENCES OF A MASSIVE FETAL GERM CELL DEPLETION ON FOLLICLE HISTOGENESIS AND EARLY FOLLICLE DEVELOPMENT IN RAT OVARIES.
Mazaud-Guittot, Severine1, 2, Guigon, Celine2, Coudouel, Noelline2, Magre, Solange2, 1 CRBR-CHUL Research Center , Laval University, Ste-Foy, QC, Canada2 CNRS-Paris VI University UMR 7079, Paris, France
ABSTRACT- Follicle histogenesis, in which follicle arise from fragmenting ovigerous cords, is a poorly understood mechanism strictly dependent on the presence of germ cells. Oocyte-depleted ovaries are characterized by the absence of fragmentation of sterile ovigerous cords and their final regression leading to streak gonads. When oocyte loss is partial, follicles, however, differentiate and mature insuring the onset of ovary functionality. In this study, we have analyzed follicle histogenesis in -irradiated ovaries at 15.5 dpc. Just after birth, in addition to sterile ovigerous cords, we observed the emergence of the first follicles. They immediately appear as primary-like follicles in which the oocyte is surrounded by a layer of cuboidal cells and thus differ from the primordial follicles observed in control ovaries in which squamous cells surround the oocyte. Granulosa cells of these primary-like follicles do not proliferate and do not display amh, activin A or aromatase gene expression normally observed in neonatal primary follicles. In contrast, oocytes grow in size and express high levels of gdf-9, which is characteristic of primary-growing follicles. There is thus no synchronization of the development of oocytes and granulosa cells. In addition, we observed a high frequency of multi-oocyte follicles (MOFs) in irradiated ovaries, and correlated this with the absence of completion of follicular unit separation. Altogether, our observations enlarge the phenotype of follicle pathologies linked to severe fetal germ cell depletion. Besides the classically described sterile cords, we point up the differentiation of primary-like quiescent follicles and MOFs which both evolve in growing follicles and participate to ovarian differentiation. We propose that these phenotypes are closely correlated to the unbalanced proportion of granulosa cells to oocytes at the time of neonatal follicle histogenesis.
KEY WORDS: follicle histogenesis, fetal irradiation, ovarian dysgenesy