Compensatory ovarian growth and compensatory ovulation after unilateral ovariectomy in rats with an ovarian autograft in the region of the portal vein.

Compensatory growth and the compensatory increase of the number of ovulations in the remaining ovary after unilateral ovariectomy were compared in three groups of rats: I. Rats with no ovarian graft. II. Rats with an ovarian autograft in the region of the portal vein. III. Rats with an ovarian autograft in a region draining into the general circulation. Compensatory growth was not inhibited by ovarian grafts placed in the region of the portal vein, whereas this was inhibited with grafts of the same volume but draining into the general circulation. This finding supports the view that compensatory ovarian growth after unilateral ovariectomy is at least partially the result of an increase in the gonadotrophin level in the blood, following the decrease in oestrogen level. In contrast, the total number of ovulations did not differ significantly in the three groups. The number of ovulations in the ovary in situ was in most cases decreased, when ovulations had occurred in the grafts, even in animals with a graft in the region of the portal vein. These findings are discussed. After unilateral ovariectomy the remaining ovary shows compensatory growth and a compensatory increase in the number of ovulations. Two mechanisms have been suggested to explain these phenomena: (1) consumption or inactivation of an increased proportion of an unchanged amount of circulating gonadotrophins by the one remaining ovary. This has been defended by * The author thanks Prof. Dr. J. Moll for his active interest and helpful advice. Downloaded from Bioscientifica.com at 12/04/2018 02:11:12AM via free access McLaren (1966), who found no increase in the gonadotrophin concentration of the hypophysis after unilateral ovariectomy, and Zarrow et al. (1965) (2) a compensatory increase in the output of gonadotrophins from the pituitary gland as the result of a decreased oestrogen secretion following the removal of one ovary (Edgren et ai. 1965). Since such an increase in the output of gonadotrophins from the pituitary gland has recently been reported (Gracly Sc Greenwald 1968; Benson et al. 1969), it was considered of interest to test the consumption theory again. The compensatory phenomena have been com¬ pared in three groups of unilaterally ovariectomized rats. I. Rats with no ovarian graft. II. Rats with an ovarian graft in the kidney or ovarian bursa. III. Rats with an ovarian graft in the vena porta region. This last type of graft in the adult rat contributes only a very small amount of oestrogens to the general circulation because of the metabolizing activity of the liver (Donovan 8c O'Keeffe 1966; Ber 1968). If the consumption theory is correct, a similar inhibition of the compensatory phenomena would be expected in rats with both types of grafts. McLarens (1966) data from a comparable ex¬ periment in mice did not provide any conclusive evidence. This she ascribed to the rapid degeneration of the grafts. MATERIALS AND METHODS The experiments were performed on adult female rats of the inbred R strain of the Netherlands Cancer Institute Amsterdam. Rats were maintained in groups of five per cage with food and water ad lib. The rat room was illuminated from 6.00 a. m. to 8.00 p. m. Vaginal smears were taken daily for at least two weeks before the opera¬ tions until the animals were killed. Operations and autopsies were always performed on the day of vaginal oestrus (almost all cells were cornified). All animals had a regular 5 day cycle before and after operation. Most of the rats were unilaterally or bilaterally ovariectomized and received an ovarian autograft. In a first experiment the grafts were placed either under the kidney capsule or in the spleen. Since ovarian grafts in the spleen had a somewhat abnormal appearance with distinct fibrosis and a reduced number of small follicles and corpora lutea, a second experiment was performed in which the grafts were placed in the ovarian bursa instead of under the kidney capsule and in the greater omentum instead of in the spleen. These grafts proved to be histologically comparable. The term ovary in situ is used only for untouched in situ ovaries, not for grafts in the ovarian bursa. In preliminary experiments it was found that during the first three cycles after unilateral ovariectomy the weight of the remaining ovary increased by 50 °/o (see also Peterson et al. 1964). During the following cycles the increase in weight was small. On the other hand, a decrease in the number of ovulations (eventually leading to a complete absence of ovulations) was observed in ovarian grafts of unilaterally ovari¬ ectomized rats during the first five cycles after the operation. Three cycles after the operation there was both a distinct compensatory ovarian growth and an active graft. Therefore the animals were killed in the third vaginal oestrus after operation. Downloaded from Bioscientifica.com at 12/04/2018 02:11:12AM via free access After killing the ovaries in situ and uteri were weighed wet. The weight of the grafts could not be determined accurately since it was very difficult to clean them from the adjacent tissue without causing damage which might cause difficulties in the histological studies. Ovaries in situ and grafts were fixed in Bouin's fluid, em¬ bedded in paraffin and sectioned. The sections were stained with haematoxylin and eosin and used for counting the number of fresh corpora lutea. All data of animals in which adhesions were found between the grafts in the vena porta region and the body wall or periovarian fat, were discarded. The statistical analysis of the results was performed using Wilcoxon's two sample test. A difference was considered as statistically significant, if the double tail pro¬ bability <¡ 0.01. The ovarian and uterine weights in the tables are given per 100 g bodyweight. Statistical evaluation of the results, however, leads to the same con¬ clusions when absolute weights are compared. OBSERVATIONS Experiment 1: Comparison of the effect of ovarian grafts of different sizes in the spleen or the kidney on compensatory ovarian growth and ovulation After the survival period of three cycles, the ovaries of unilaterally ovari¬ ectomized rats showed a mean increase in weight of about 50 °/o. The mean number of corpora lutea showed a two fold increase (Table 1, groups 1 and 2). The inhibitory effect of ovarian grafts in the kidney on compensatory growth of the ovary in situ was very marked, when 1/1 or 1/2 ovary was grafted. When, however, 1/10 ovary was grafted to the kidney we found no inhibition. Absence of inhibition was also found with grafts in the spleen independently of their volume. Rough estimations of the weight of the grafts yielded values of 8-11 mg when 1/1 or 1/2 ovary was grafted and 0.5-2 mg when 1/10 ovary was grafted. We did not find a tendency for kidney ovaries to have a higher weight than spleen ovaries. Rough estimates of the volume of the grafts from histological sections too did not show any difference between spleen and kidney ovaries. The total number of fresh corpora lutea per animal (in in situ and, if present, in grafted ovaries) did not differ significantly between the control and experimental groups, although a considerable variation was observed. The number of fresh corpora lutea in the ovaries in situ was significantly higher without grafted ovaries than with 1/1 or 1/2 ovary grafted to the kidney or 1/1 ovary grafted to the spleen (Table 1, groups 2, 3, 4 and 6). The mean uterine weight was significantly higher in the groups with spleen ovaries than in the other groups. Experiment II: Comparison of the effect of ovarian grafts in ovarian bursa and greater omentum on compensatory ovarian growth and ovulation The histological appearance of ovarian grafts approached the normal conDownloaded from Bioscientifica.com at 12/04/2018 02:11:12AM via free access