The Microenvironment of the Human Antral Follicle: Interrelationships among the Steroid Levels in Antral Fluid, the Population of Granulosa Cells, and the Status of the Oocyte in Vivo and in Vitro *

Abstract

A number of parameters in human antral follicles were investigated. They were: the number of granulosa cells in each follicle; the concentrations of progesterone, androstenedi-one, testosterone, dihydrotestosterone, estrone, and 17β-estra-diol in antral fluid; and the status of the oocyte immediately after removal from the follicle and again after 48 h in culture. In addition, the phase of the menstrual cycle at the time of ovariectomy and the diameter of each dissected follicle were recorded. The number of granulosa cells present in each follicle and the viability of the oocyte before culture as well as its subsequent in vitro behavior were correlated with the concentration of estra-diol and⁄or the ratio of androgen to estrogen in antral fluid. It is tentatively suggested that follicles with a potential for further development are those with 1) more than 50‰ of their full complement of granulosa cells for their respective diameters, 2) high concentrations of 17β-estradiol (≥1000 ng⁄ml) in their antral fluid and⁄or granulosa cells with the capacity to generate this steroid in response to FSH, and 3) a germinal vesicle stage oocyte which appears healthy at the dissecting microscope level. Follicles incapable of further development are suggested to be those containing 1) less than 50‰ of their full complement of granulosa cells for their respective diameters and 2) low concentrations of 17β-estradiol in their antral fluid and granulosa cells incapable of responding to FSH to generate high levels of intra-follicular estradiol. Many of these follicles are likely to contain degenerating oocytes and⁄or one that is incapable of meiotic maturation invitro. The incidence of antral follicle atresia in human ovaries at every stage of the menstrual cycle was high, since approximately 90‰ of follicles ≥1mm in diameter were undergoing some kind of degeneration, as assessed by the number of granulosa cells per follicle diameter and the viability of the oocyte at recovery. During the menstrual cycle, it was estimated that only one, or in some cases two, antral follicles continued to generate a full complement of granulosa cells after reaching a diameter of ∽4 mm. In addition, it was concluded that the follicular phase of the menstrual cycle is associated with the relatively late stages of development of the ovulatory follicle, since the largest nona-tretic follicle at the onset of the follicular phase had attained a diameter of 4 mm. These data provide tentative criteria for a functional assessment of growth and atresia of human antral follicles. Moreover, they add further evidence to suggest that the hormonal microen-vironment of the follicle is a key factor in determining its subsequent development.