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[Histology and histochemistry of the seal ovaries and the age-related changes in the ovaries of the Greenland seal].

Histological and histochemical methods were used to study the ovaries of Greenland seal (Pagophoca groenlandica) from birth-time up to 30 years of age and mature females of Phoca vitulina and Erignathus barbatus. The ovary of the new-born Greenland seal has fetal medullary substance which is a provisory endocrinous gland producing not only sex hormones but also corticosteron. In other species of seals the intestinal cells of the medullary substance are the equivalent of this gland. Within 3-4 weeks after birth the reduction of the fetal medullary substance is completed, it is substituted by the connective tissue and the ovary acquires its typical structure. The rest of the fetal medullary substance is in the depth of the cortex and near the infundibulum of the ovary as lipofuscincontaining cells. When the maturation period approaches, the process of the follicle atresia regularly changes: the epithelium dies quicker, and the multiplication of intestinal cells increases. The ovaries of seals are rich in interstitial cells. Their amount cyclically changes. The cells producing steroid hormones always well hydrolize AS naphthyl-phosphates, the reaction with glycerophosphate is more variable. The connective tissue is poor in acid mucopolysaccharides, its amorphous substance in the ovary cortex is rich in protein. Senile changes of the ovary are noticed in the seal beginning from 20 years of age.

Age Factors

The silent ovary: a five year survey of cancer of the ovary at the Hutt Hospital 1973-1977.

Cancer of the ovary is the leading cause of death from gynaecological cancer. Forty-six cases are reported to re-emphasise certain features. These include the short history and the high mortality rate regardless of what treatment is used. Whereas improvement has occurred in the treatment of cancer of the corpus and the cervix, there has been no improvement over two decades in cancer of the ovary. The moral of this tale, is to advise your women folk to avoid cancer of the ovary.

Adolescent

Ovaries and adrenals in murine Schistosomiasis mansoni. I. Histopathological changes of the ovaries in acute and chronic infection.

Acute and chronic infections with schistosomiasis mansoni in mice were found to cause a reduction of the ovarian weight and atrophy of the corpus luteum cells, followed by lymphocytic and stroma cell infiltration. Finally, the corpora lutea disappeared completely. Acute schistosomiasis caused arrested development of the corpora lutea. Both acute and chronic schistosomiasis led to the formation of "wheel cells" in the interstitial tissue of the ovaries. A threshold level of intensity of disease was found to be necessary for these pathological changes. With less severe schistosomiasis, the morphology of the corpora lutea remained normal. The more intensive and long-lasting the infection, the greater became the atrophy of corpora lutea. The various factors which could have caused these pathological alterations are discussed in the light of available literature, and it is suggested that a pituitary hypofunction, and particularly a lack of luteinizing hormone effect, may play a role in the pathological transformation of the ovarian tissue.

Acute Disease

Ovaries and adrenals in murine Schistosomiasis mansoni. II. Some observations on the function of the ovaries in acute infection.

In mice with acute schistosomiasis mansoni the mean serum level of progesterone, as determined by radioimmunoassay, was significantly lower than in non-infected control animals, probably due to the atrophy of corpora lutea and the discontinuance of their development described in an earlier paper. In spite of the histopathological changes in the ovaries and the decreased level of progesterone in the blood, estrus was present in some infected animals.

Animals

Histologic study of ovaries from young women with endometrial adenocarcinoma.

A histologic study of 15 ovaries from patients in whom endometrial adenocarcinoma developed before the age of 40 years was performed. These ovaries were randomized with control groups of 21 age-matched normal ovaries and 25 ovaries from patients who had Stein-Leventhal syndrome. The study was done in an attempt to determine whether the ovaries from these young patients showed any histologic feature that would indicate abnormal ovarian function resulting in unopposed estrogenic stimulation of the endometrium. Histologic features assessed included type and size of cysts, presence and number of primary follicles, corpora lutea, corpora albicantia, and presence of stromal luteinization and sclerosis. Analysis of the results indicated that from a histologic point of view ovaries of patients less than 40 years old who have endometrial adenocarcinoma are more similar to normal ovaries than to polycystic ovaries. Only 11.1% of ovaries of the study group had features suggestive of polycystic ovarian disease.

Adult

Pattern of follicular growth and steroidogenesis in the ovary of aging cycling rats.

Prior to the cessation of reproductive cycles, older female rats exhibit irregular and prolonged cycles due to alterations in the hypothalamic-pituitary-ovarian axis. In order to evaluate the age-related changes in the ovary, the histology, and estradiol, testosterone and progesterone concentrations within the ovaries of mature regular cycling (4--5 mo. old) and older irregular cycling (10--11 mo. old) rats were examined. At estrus, the number of non-atretic growing follicles (150--300u in diameter) was greater in the mature than in the older rats (18 +/- 1.5 vs 4.5 +/- 1.4). However, the number of preovulatory follicles on proestrus did not differ (6.0 +/- 1.2 vs 5.5 +/- 0.6). Estradiol, testosterone and progesterone concentrations on proestrus in mature rats averaged 38.8 pg, 56.1 pg, and 1.0 ng/ml of ovary, respectively. In the older proestrous rat, only estradiol was altered, increasing to 124.3 pg/mg. In addition, many of the preovulatory follicles within the aged ovary were larger (greater than 600u in diameter) than those within the mature ovary. On the day of estrus virtually all preovulatory follicles ovulated in the mature rat, whereas large follicles, less than or equal to 600u in diameter, remained in the older ovary. In addition, estradiol levels remained elevated and ovarian cysts were observed in the aged ovary. Thus, in the older irregular cycling rat, 1) pre-ovulatory follicles develop, but many do not ovulate; 2) these non-ovulatory follicles form ovarian cysts which remain within the ovary. The number of cysts may increase with age until a polycystic ovary develops and the rat enters a constant estrous state.

Aging

Between-ovary interaction in the regulation of follicle growth, corpus luteum function, and gonadotropin secretion in the primate ovarian cycle. III. Temporal and spatial dissociation of folliculogenesis and negative feedback regulation of tonic gonadotropin release after luteectomy in rhesus monkeys.

This study was designed to examine effects of previous ovarian status on subsequent follicle growth and the role of between-ovary communication in the regulation of folliculogenesis and gonadotropin secretion during the primate ovarian cycle. Responses to luteectomy were compared in two groups of rhesus monkeys. In the first, follicle growth and corpus luteum function had been constrained chronically to a single ovary by hemiovariectomy performed 66--258 days earlier; the second group was composed of intact monkeys that underwent contralateral wedge resection at luteectomy. In each group, luteal ablation was followed by a prompt fall in serum progesterone levels, a premature onset of menses, and the next preovulatory gonadotropin surges 14.7 +/- 1.1 or 15.4 +/- 1.4 days later (mean +/- SE; P greater than 0.25). Although the patterns of circulating estradiol before and after ablation in each group were superimposable, luteectomy in monkeys lacking a contralateral ovary was followed by a large (2- to 4-fold) and prolonged (7--10 days) increase in serum FSH, whereas in monkeys with two ovaries, serum FSH levels exhibited only a small short-lived rise. The findings indicate that 1) prior chronic constraint of ovarian function to a single ovary did not alter the overall time course of new follicle growth culminating in ovulation after luteectomy; 2) the contralateral ovary provided the principal negative feedback regulation of gonadotropin secretion for some time after luteectomy even though it may not have been the exclusive site of new follicle growth; 3) whereas the ability of the luteectomized ovary to regulate tonic gonadotropin secretion was temporarily impaired, its ability to support the customary temporal pattern of follicle growth after luteal ablation was not; 4) some (contralateral) ovarian factor other than estradiol or progesterone apparently made a major contribution to the regulation of FSH secretion after luteectomy; and 5) folliculogenesis culminating in ovulation from a single follicle and the negative feedback regulation of tonic gonadotropin secretion in some circumstances may occur concurrently but separately on opposite ovaries or may occur at different times within the same ovary.

Animals

Examination of the role of follicle stimulating hormone in estrogen biosynthesis in vivo and in vitro in the ovary of the cyclic hamster.

The effect of neutralizing endogenous follicle stimulating hormone (FSH) or luteinizing hormone (LH) with specific antisera on the in vivo and in vitro synthesis of estrogen in the ovary of cycling hamster was studied. Neutralization of FSH or LH on proestrus resulted in a reduction in the estradiol concentration of the ovary on diestrus-2 and next proestrus, suggesting an impairment in follicular development. Injection of FSH antiserum at 0900 h of diestrus-2 significantly reduced the ovarian estradiol concentration within 6--7 h. Further, these ovaries on incubation with testosterone (T) in vitro at 1600 h of the same day or the next day synthesized significantly lower amounts of estradiol, compared to corresponding control ovaries. Although testosterone itself, in the absence of endogenous FSH, could stimulate estrogen synthesis to some extent, FSH had to be supplemented with T to restore estrogen synthesis to the level seen in control ovaries incubated with T. Lack of FSH thus appeared to affect the aromatization step in the estrogen biosynthetic pathway in the ovary of hamster on diestrus-2. In contrast to this, FSH antiserum given on the morning of proestrus had no effect on the in vivo and in vitro synthesis of estrogen, when examined 6--7 h later. The results suggest that there could be a difference in the need for FSH at different times of the cycle. Neutralization of LH either on diestrus-2 or proestrus resulted in a drastic reduction in estradiol concentration of the ovary. This block was at the level of androgen synthesis, since supplementing testerone alone in vitro could stimulate estrogen synthesis to a more or less similar extent as in the ovaries of control hamsters.

Animals

Studies on sex-organ development. The hormonal regulation of steroidogenesis and adenosine 3':5'-cyclic monophosphate in embryonic-chick ovary.

1. We investigated the production of steroid hormones by the ovaries of the developing embryonic chick under conditions of organ culture. Radioimmunoassay techniques were used to measure the amount of steroid hormone released into the culture medium. Stimulation of the production of steroid hormones by choriogonadotropin from the urine of pregnant human was dose-dependent. Oestradio and testosterone production was optimal when 20 i.u. of gonadotropic hormone was present in the culture medium 2. During development, both left and right ovaries responded to gonadotropic hormone stimulation with a 2.5-3-fold increase in oestrogen production. However, the right ovary was twice as efficient in testosterone production as the left one. The presence of dibutyryl cyclic AMP in the culture medium of the embryonic ovaries mimicked the effect of the gonadotropic hormone. 3. The human choriogonadotropic hormone stimulated cyclic AMP production in the embryonic ovarian tissue. Thyrotropin, growth hormone and insulin had no stimulating effect. 3-Isobutyl-1-methylxanthine potentiated the gonadotropic hormone effect by increasing the concentration of cyclic AMP in the ovarian tissue. 4. The amount of cyclic AMP synthesized in the embryonic ovary was gradually increased (from 1.2 to 6.5 pmol/mg of tissue) when incubated with increasing doses of human choriogonadotropic hormone in vitro. The newly synthesized cyclic AMP reached the maximum concnentration after 30 min of incubation, then decreased at 2 h of incubation. A portion of the newly synthesized cyclic AMP was released into the culture medium. 5. At various developmental stages, both left and right embryonic-chick ovaries responded to stimulation by gonadotropic hormone with an increase in cyclic AMP production. The cyclic AMP concentration in the right ovary was 80% higher than that in the corresponding left ovary.

Animals

Morphological study of the ovaries of leukaemic children.

The ovaries of leukaemic children were studied in 31 specimens obtained at autopsy. Twenty-eight ovaries from normal children of the same age who died from misadventure served as control. All ovaries from normal childred showed follicle growth and contained several large antral follicles. Follicle development was inhibited in all ovaries of leukaemic children; 22% showed no follicle growth (quiescent ovaries), and in the ovaries in which there was follicle development, the number and size of antral follicles was significantly smaller than in the control. All children had been treated with cytotoxic drugs, the duration of the treatment being correlated with the stage of ovarian development. The ovaries of children treated for only 1 week were near-normal, while those treated for more than 2 months showed inhibition of follicle growth. It is argued that the disturbance in follicle development is an effect of the cytotoxic drugs, and not an effect of the disease itself.

Acute Disease

Prevention of compensatory ovarian hypertrophy by local treatment of the ovary with 6-OHDA.

The possible role of a neural mechanism involved in the development of compensatory ovarian hypertrophy has been studied. A new technique, the use of a special plastic capsule, has been developed to allow chronic local treatment of the ovary. Local treatment of one of the ovaries with 6-hydroxydopamine (6-OHDA) resulted in a weight increase in the other ovary. In the unilaterally ovariectomized rat the local application of 6-OHDA on the ovary blocked the development of compensatory ovarian hypertrophy. Local treatment of the ovary with dopamine (DA) did not interfere with the compensatory ovarian growth of the other ovary. Data suggest that intact adrenergic afferent and efferent neural elements of the ovary are required for the development of compensatory ovarian hypertrophy.

Animals

[Studies on the RNA synthesized in the ovary of immature rats after HCG administration (author's transl)].

Although many researchers have reported that RNA synthesis in the ovary is enhanced by gonadotropin treatment, there are only a few papers concerning the character of newly synthesized RNA after gonadotropin treatment. In this paper, the RNA synthesized in the ovary of immature rats after HCG treatment was qualitatively studied. Immature female Sprague-Dawley rats were administered with 0.3 mc per rat of 3H-uridine at a certain time interval after injection of HCG (10 iu/rat) and the ovaries were subsequently isolated after 15, 30 or 60 minutes. RNA was extracted from the homogenate of the ovaries according to the hot phenol method after Scherrer and Darnell. The 3H-RNA thus extracted was treated with electrophoretically purified DNase to break down and remove DNA that mingled with it. The RNA solution ultimately obtained was analysed on a 3-20% sucrose gradient. The different fractions thus separated were then subjected to measurement of radioactivity and optical density at 260 mmug. The RNA extracted from the ovary of immature untreated rat labeled with 3H-uridine for 15 minutes showed a flat pattern of radioactivity from the top to the bottom fractions with low radioactivity. Otherwise, when labeled for one hour, the RNA showed a pattern of radioactivity like those of optical density at 260 mumu with peaks of r-RNAs and t-RNA. When the ovary was pulse-labeled with 3H-uridine for 15 minutes starting 2 hours after injection of HCG, the RNA with a large S value was synthesized and the pattern of variation in radioactivity was that of rising near the bottom fraction and declining with access to the top fraction. The results obtained by labeling for 15 minutes starting 40 hours after PMS administration were similar to those obtained in immature untreated rats. The patterns of radioactivity in RNA obtained by the labeling for 15 minutes starting 2 hours after HCG and 42 hours after PMS were similar to those starting 2 hours after only HCG injection. The patterns of radioactivity became similar to those of optical density at 260 mmu, when the ovaries were labeled for 30 or 60 minutes. From these results, it was suggested that the newly synthesized RNA 2 hours after HCG was constructed from m-RMA with rapid turn over and precursors of r-RNAs and t-RNA. This RNA synthesis was blocked by pretreatment with actinomycin but not by cycloheximide. From these results, it was suggested that enhancement in RNA polymerase activity or change in template capacity of DNA which would have an effect on RNA synthesis was not based on newly synthesized protein.

Animals