Morphological and Endocrinological Studies on Follicular Development during the Human Menstrual Cycle*

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Abstract
In order to clarify the morphological dynamics of follicular development and its correlation with ovarian endocrine activity, the present studies were performed in 45 regularly menstruating women who underwent gynecological surgery. Ovarian venous blood was collected from 35 women during the follicular phase. Thirteen of these 35 women were ovariectomized. In addition, 11 pairs of ovaries were obtained from women during the luteal phase. The ovaries were sectioned serially at 2.5 μm and every 13th stained slice was examined to assess the sizes and numbers of atretic and nonatretic follicles. The follicles were divided into five stages: 0.4 ≦ ∼ <1.0 mm, 1.0 ≦ ∼ < 2.0 mm, 2.0 ≦ ∼ < 4.0 mm, 4.0 ≦ ∼ < 6.0 mm, and 6.0 mm ≦ ∼ in follicular diameter. Estradiol concentrations in ovarian venous plasma were low on both sides on days 1 and 3 of the cycle, whereas a clear asymmetry was found on day 5 before morphological recognition of the dominant follicle. Thereafter, estradiol increased proportionally to the growth of the dominant follicle, followed by a sudden drop when ovulation was imminent. An asymmetrical rise of progesterone occurred on day 10 and later which was sustained up to ovulation. A dominant follicle was recognized in 8 of 11 women between days 6 and 14. All dominant follicles were invariably associated with higher estradiol concentrations in the ipsilateral ovarian blood. Seven of 8 dominant follicles were on the side contralateral to the preceding corpus luteum. The mean diameters of the largest nonatretic follicles were 5.4 ± 0.3 (SE) mm during the luteal phase as a whole and 4.7 ± 0.7 mm during the late luteal phase. The mean diameters of the largest nonatretic follicles were not significantly different between the groups with or without the corpus luteum in the luteal phase. In terms of number and atretic rate, follicles of less than 4.0 mm in diameter did not change throughout the cycle in the presence or absence of the corpus luteum. In contrast, cyclic changes of growth and atresia occurred in the larger antral follicles. These data suggest that: 1) the atretic rates and numbers of follicles of less than 4.0 mm in diameter do not vary through a cycle, 2) a dominant follicle seems to develop from among a few follicles with a mean diameter of 4.7 ± 0.2 (SE) mm and acquires predominance initially in estrogen-secreting activity, followed by rapid follicular growth, and 3) the corpus luteum may have minor inhibiting local effects on recruitment of a dominant follicle despite its lack of apparent influence on smaller antral follicles.

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