Previous studies have demonstrated the involvement of eicosanoids (prostaglandins and hydroxyperoxides, including leukotrienes) in ovulation in several mammalian species. In this study, the role played by eicosanoids in the vascular changes that occur in the immediate preovulatory period after human chorionic gonadotropin (hCG) stimulation was examined in the rat. Changes in the ovarian uptake of two iodinated proteins were examined 30 minutes after i.v. injection of 125I-bovine serum albumin (BSA, Mr = 68,000) and 125I-alpha 2-macroglobulin (alpha 2M, Mr = 750,000). Uptake was measured during 30 min, 0, 3, 6, and 9 h after induction of ovulation by an i.p. injection of human chorionic gonadotropin (hCG, 10 IU). hCG enhanced the uptake of both iodinated proteins, with peak uptake values at 6 and 9 h. Intra-bursal injections of an ovulation inhibiting dose (0.5 mg/bursa) of indomethacin-a cycooxygenase inhibitor-and nordihydroguaiaretic acid (NDGA), esculetin, or caffeic acid--inhibitors of lipoxygenase--concomitantly with hCG attenuated the action of the hormone on 125I-BSA uptake. Indomethacin and esculetin were without effect on the uptake of alpha 2M. Ovarian and follicular blood flow was measured using 113Sn-microspheres. hCG increased ovarian and follicular blood flow with the most pronounced effect at the early time of 1.5 h. Indomethacin and NDGA did not attenuate this action of hCG. Accordingly, ovarian vascular resistance was reduced by hCG at 1.5, 6, and 9 h post-hCG, respectively, and indomethacin and NDGA had no significant effects. We suggest that one way in which eicosanoids are involved in follicular rupture is by their modulation of vascular permeability as revealed by uptake of the protein marker albumin.

The growth of tertiary follicles, i.e., the proliferation of cells in the stratum granulosum and in the capillary network of the theca interna, after injection of ovulation-inducing human chorionic gonadotropin (HCG), was investigated in the rabbit by means of autoradiographic and morphometric methods. Based on the frequency distribution of follicles with different sizes and on the labeling index (LI) of granulosa cells as a function of follicle size and of time prior to and after HCG stimulation, two groups of tertiary follicles can be distinguished: growing (250-900 micron in diameter) and mature (greater than 900 micron in diameter) elements. The growth of both groups is influenced by the release of gonadotropins. After HCG stimulation, follicles belonging to the first group grow rapidly. During, and a short time after ovulation, almost all non-ruptured follicles larger than 600 micron in diameter become atretic. Within 35-50 h the ruptured and atretic mature follicles (greater than 900 micron in diameter) are replaced by follicles out of the group of growing follicles. From these results the following concept for regulation of follicle growth is derived: In principle, all growing follicles possess the potential to develop into mature follicles. When a sufficient number of mature follicles is generated, these mature follicles determine the number of succeeding growing follicles. Follicles that are not required for providing mature follicles become atretic as soon as they reach a diameter of 700 micron. When the majority of mature follicles is lost during ovulation (by rupture or atresia), this inhibition regulated by mature follicles is abolished, and all of the growing follicles again are capable to develop into mature follicles. The relative amount of capillaries in the theca interna of growing and mature follicles remains constant with increasing follicle size. This means that the capillary network grows parallel to the increasing size of follicles. No differences are found between intact and atretic follicles; advanced atretic follicles were excluded from this study. The labeling index (LI) of granulosa cells in the stratum granulosum and of endothelial cells in the theca interna, as a function of follicle size and of time after HCG stimulation, are closely correlated. A change in the LI of granulosa cells is usually followed with a certain delay by a similar alteration of the LI of endothelial cells in the theca interna. This suggests that granulosa cells have a certain regulatory function on capillary growth.

Transient lymphopenia is a hallmark of measles virus (MV)-

No abstract

The aim of this study was to evaluate morphometrically the influence of ovulation-inhibiting doses of indomethacin, an inhibitor of the cyclooxygenase pathway, and esculetin and caffeic acid, inhibitors of the lipoxygenase pathway, on the dilatation of the perifollicular capillary network in the theca interna. The development of the perifollicular capillary network as a function of follicular size and the changes in the vascular lumen were examined by light microscopy on a series of semithin cross sections of rat ovaries. The number of capillaries in the theca interna increased linearly with increasing follicle diameter. Thus, the relative number of capillaries in the theca interna supplying the avascular stratum granulosum remained constant. This indicates that follicular function is not regulated through changes in the number of capillaries in the theca interna. After hCG injection, an increase in the capillary area could be observed in follicles having a diameter of more than 600 microns. Indomethacin administration increased the capillary area of the ovulatory follicles as compared to the untreated side only at 6 h after treatment. By contrast, treatment with inhibitors of lipoxygenase resulted in a significant decrease in the capillary area of large follicles at all times examined (3, 6, and 9 h after hCG injection). Nevertheless, since both types of eicosanoid inhibitors suppressed follicle rupture, in spite of their opposing actions on the capillary area, it seems unlikely that their action on ovulation is primarily due to their effect on this parameter.