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Healthy and Atretic Human Follicles in the Preovulatory Phase: Differences in Evolution of Follicular Morphology and Steroid Content of Follicular Fluid^*

O. BOMSEL-HELMREICH, A. GOUGEON, A. THEBAULT, D. SALTARELLI, E. MILGROM, R. FRYDMAN and E. PAPIERNIK

Université de Paris-Sud Paris, France

Address requests for reprints to: Dr. O. Bomsel-Helmreich, Laboratoire de Physiologie de la Reproduction Humaine, Service de Gynécologie-Obstetrique, Hopital A. Béclère, 92141 Clamart, France.

A comparative study was performed on large follicles in the human ovary obtained during the preovulatory period. Size and type of follicle (normal or atretic) and morphology of the granulosa cells were correlated for each follicle with enzymatic activity and steroid content.

The true preovulatory follicle was characterized by a pycnotic index which never exceeded 2.0/ml, whereas this index was significantly higher (5–10/ml) in early atretic follicles.

For the healthy preovulatory follicle, it was possible to establish a precise chronological sequence of events preceding ovulation. The preovulatory period from day –5 before LH peak (day 0) to ovulation was divided into three discrete phases. In phase I (from the beginning of the estrogen surge to the estrogen peak in plasma), the preovulatory follicle initially contained 4.3 ± 1.6 pmol/µl (mean ± SE; 6 follicles) estradiol, increasing to 9.3 ± 1.1 pmol/µl (mean ± SE; 5 follicles). Progesterone content was 1.6 ± 1.3 pmol/µl (mean ± SE; 11 follicles). In phase II (between estrogen and LH peaks), estradiol content reached 9.0 ± 4.2 pmol/µl (mean ± SE; 4 follicles), with a peak value of 14.0 ± 0.1 pmol/µl, while progesterone rose to 7.6 ± 1.8 pmol/µl (mean ± SE; 4 follicles). Phase III (between LH peak and ovulation) was characterized by a drop in estradiol (3.0 ± 1.8 pmol/µl; mean ± SE; 8 follicles), whereas progesterone rose dramatically (25.8 ± 10.9 pmol/µl; mean ± SE; 8 follicles), with a peak value of 45.0 ± 2.7 pmol/µl. 3/β-Hydroxysteroidoxidoreductase activity increased in the theca interna until the estrogen peak, but decreased slightly in phase III. In the granulosa, the above enzymatic activity was moderate in phase I and became very strong at ovulation. Morphological changes in the granulosa included centripetally oriented granulosa cells which formed a basal layer in phase I, progressive histologically defined preluteinization and disorganization of the granulosa in phase II, and appearance of lacunae and red blood cells in phase III.

In early atretic follicles, steroid concentration in follicular fluid was very low (1.4 ± 1.3 pmol/µl for estrogen and 0.6 ± 0.4 pmol/µl for progesterone; mean ± SE; 16 follicles).

This description of the preovulatory follicle may be used to compare normal follicles with those in pathological situations.

^* This work was supported by grants from the INSERM and University Paris-Sud, UER Kremlin Bicêtre.

Present address: Laboratoire de Physiologie de la Reproduction Humaine, Service de Gynécologie-Obstétrique, Hôpital A. Béclère, 92141 Clamart, France.

Present address: Groupe de Recherches sur la Biochimie Endocrinienne dé la Reproduction (INSERM U 135), 94270 Bicêtre, France.

Present address: Service de Gynécologie-Obstétrique, Hôpital A. Béclère, 92141 Clamart, France.

Received October 11, 1977.

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