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Establishment of the Reproductive Function and Transient Fertility of Female Rats Lacking Primordial Follicle Stock after Fetal -Irradiation

Laboratoire de Physiologie et Physiopathologie, Centre National de la Recherche Scientifique-UMR 7079, Université Paris VI (S.M., C.J.G., A.L., N.C., S.M.), Paris, France; Institut National de la Santé et de la Recherche Médicale, U-329, Hôpital Debrousse (M.G.F.), 69322 Lyon, France; and Département de Radiobiologie et Radiopathologie, Commissariat à l’Energie Atomique (H.C.), 92265 Fontenay-aux-Roses, France

Address all correspondence and requests for reprints to: Dr. S. Magre, Laboratoire de Physiologie et Physiopathologie, UMR 7079, Université Paris VI, 7 quai Saint-Bernard, 75005 Paris, France. E-mail: solange.magre{at}snv.jussieu.fr

In mammals, the primordial follicle stock is not renewable, and its size, therefore, limits the reproductive life span of the female. In this study we have investigated the morphological and functional differentiation of dysgenesic ovaries in female rats exposed in utero to 1.5 Gy -irradiation. As a consequence of the severe depletion in oocytes, females evidenced premature ovarian failure from 6 months on. Nevertheless, puberty onset and fertility at the beginning of reproductive life were similar to those of controls.

The differentiation and evolution of the entire follicular population were followed during the immature period, using follicle counts, in situ hybridization of follicular maturation markers, and analysis of atresia. Primordial follicles were much more affected by irradiation (1.4–1.9% of controls) than growing follicles (30–45% of controls). As the very low number of primordial follicles remained constant throughout this period, it may be considered that the growing follicle pool plays the role of follicular reserve, permitting the transient normal fertility of irradiated females. Within the neonatal period, primary and secondary follicles, as revealed by proliferating cell nuclear antigen immunostaining, remain quiescent longer in irradiated than in control ovaries. Consequently, the majority of the most mature follicles (i.e. the first follicular wave) characterized by a high expression of aromatase transcripts during the infantile period, are missing in irradiated ovaries. Concomitantly, the 17ß-estradiol plasma peak is absent, and plasma FSH levels are higher than those in control females.

In conclusion, these observations emphasize that the female reproductive life span depends not merely on the size of the primordial follicle stock, but also on the entire follicle complement as well as follicular dynamics during the immature period.

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