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Unaltered Development of the Initial Follicular Waves and Normal Pubertal Onset in Female Rats after Neonatal Deletion of the Follicular Reserve

Laboratoire de Physiologie et Physiopathologie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7079, Université Pierre et Marie Curie (C.J.G., S.M., N.C., S.M.), 75005 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité (U)-329, Laboratoire de Pathologie Hormonale Moléculaire, Hôpital Debrousse (M.G.F.), 69322 Lyon, France; and INSERM, U-135, Laboratoire d’Hormonologie et Biologie Moléculaire, Hôpital de Bicêtre (S.B.-T.), 94275 Le Kremlin Bicêtre, France

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

In rats, the pool of primordial follicles is established within the first 3 d postnatally (dpn). Immediately after their differentiation, a subset of follicles begins to grow and constitutes the initial follicular waves. In this study we investigated the development of these early growing follicles after deletion of the primordial follicle pool induced by 1.5 Gy -irradiation at 5 dpn. Within only 24 h, i.e. at 6 dpn, 99% of the primordial follicles disappeared, whereas most of the growing follicles remained unaffected. The study of these surviving follicles throughout the immature period has shown that their subsequent growth proceeded normally, as assessed by proliferating cell nuclear antigen immunostaining and follicular counts. No modification in the process of follicular atresia, studied by terminal deoxynucleotidyltransferase-mediated deoxy-UTP-fluorescein nick end labeling and Southern blot of DNA fragmentation analysis, was observed. Complementary analysis, by either in situ hybridization for inhibin subunits, P450 aromatase, and LH receptor mRNAs or plasma dosages of 17ß-estradiol and inhibin B, further showed that follicular maturation was unaltered. In line with these observations, pubertal onset was normal, regarding both age and ovulation rate. Nevertheless, as a consequence of the nonrenewal of the growing pool, the follicular complement was practically exhausted at puberty, and 90% of the females evidenced sterility by 4 months. Altogether, our results demonstrate that the deletion of the primordial follicle pool has induced no modification in the growth pattern of the early growing follicles that develop as their counterparts in control ovaries. Within the immature period, the initial follicular waves ensure the ovarian functionality and thus play a key role in the initiation of reproductive life.

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