Decrease In Ovarian Weight Research Articles

The Extract of Tristania Sumatrana Miq. to Lower Primary, Secondary and Tertiary Follicles in Swiss Webster Mice

The use of traditional medicinal plants is generally based on empirical experience; therefore, a scientific approach is needed to bring traditional medicine into the practice of medicine and formal health services. Tristania sumatrana Miq. is one of the traditional medicinal plants that are often used as contraceptives for women in the villages of Lembah Bawan and Kampung Dalam (West Sumatra). The extract of Tristania sumatrana Miq. can extend the estrus cycle of Mus musculus into eleven days. The purpose of this research is to know the effect of Tristania sumatrana Miq. extract to the fertility of female mice. The experiments were conducted with a randomized 5x2 group design. Five dosage groups: untreated control, placebo, treatment with doses 600, 900 and 1200 mg/kgbw and two treatment groups: 10 and 20 days. The fertility parameters studied were ovarian weight, number of primary, secondary, tertiary follicles. The results prove the extract of Tristania sumatrana Miq. causing a very significant decrease in ovarian weight (treatment of 900 mg/kg bb for 10 days), number of primary and secondary follicles (1200 mg / kg bb for 10 days), and tertiary (600 mg / kg bb for 20 days). The extract of Tristania sumatrana Miq. causing a decline in Mus musculus fertility.

Evaluation of Ovulation Inhibition Properties of a Phytoestrogen Isolated from Momordica charantia Linn. Seeds

Background and objectives: Momordica charantia Linn. has been used as a dietary / medicinal supplement for health care. The plant has a long history in worldwide people for the usage of vaginal discharge, to promote menstruation and to induce abortions. However, the mechanism of action for its ovulation inhibition effects is not clearly known. Therefore, the present study was carried out to evaluate the ovulation inhibition properties of phytoestrogenic molecule isolated from M. charantia seeds in albino rats as an experimental model. Methods: Ovulation inhibition properties of fractions of ethanol extract and phenolphthalein a phytoestrogenic molecule isolated from seeds of Momordica charantia Linn. were evaluated in fertile female albino rats. In the first batch of animals having groups I, II, III, IV were treated with 15 and 25mg/100g oral doses of Fraction I and Fraction II and group V served as control. In the second batch of animals having groups I, II, III was treated with 10, 15 & 20mg/100g isolated phenolphthalein and group IV served as control. Results: At autopsy on day 31st, decrease in ovarian weight and histological studies shows highly significant decrease in number of developing follicles, Graafian follicles, corpora lutea and significant increased in number of atreatic follicles is observed in Fraction I and phenolphthalein treatment. There are no appreciable changes are observed in the above parameters when both the doses of Fraction II administration. Interpretation and Conclusions: The study results suggested that M. charantia seed fractions and phenolphthalein possess ovulation inhibition properties in experimental animals. Interestingly, in recent years, the popularity of different kinds of pharmaceutical preparations containing phytoestrogens has constantly increasing. Therefore, studies of the influence of the above mentioned plant components on female reproduction have become more and more important. This leads to discovery of newer phytoconstituents with better activities and provide source of new biomolecules for biologists to work on. The studies explore the utilization of medicinal plants for effective management of contraception. It gives a larger platform for the medicinal plant growers by providing scientific support and data to the traditional invalidated herbal drugs. Taking account of all these facts, the present study was undertaken in albino rats.

Administration of a Gonadotropin-Releasing Hormone Agonist Affects Corpus Luteum Development, Angiogenesis, and Induces Apoptosis in a Rat Model of Ovarian Hyperstimulation Syndrome.

Moderate to severe ovarian hyperstimulation syndrome (OHSS) has been calculated to occur in 0.2% to 2% of all ovarian stimulation cycles. Risk factors include low body weight, high follicle count, polycystic ovarian syndrome, previous OHSS and elevated serum estradiol. Gonadotropin-releasing hormone analogs are thought to be effective in preventing this complication and several clinical trials have found lower incidence of OHSS in patients treated with these molecules. Our objective was to analyze the in vivo effect of GnRH-I agonist on corpus luteum (CL) development, angiogenesis, luteal regression and cell proliferation in ovaries from rat OHSS model. Group OHSS (hyperstimulated immature Sprague Dawley rats) received excessive doses of pregnant mare serum gonadotropin (PMSG, 50 UI/day) injected for 4 consecutive days (from the 21th day to 24th of life), followed by human chorionic gonadotropin (hCG, 25 UI, 25th day of life). Group OHSS + GnRH-I a (GnRH-agonist treated hyperestimulated immature rats) received the same doses of gonadotropins than in group OHSS and, in turn, received injections of GnRH-I a for 5 consecutive days (Leuprolide Acetate, 100 µg/kg/day, from the 21th to the 25th day of life; twice a day), followed by hCG (25 UI, 25th day of life). Immature female Sprague Dawley rats were hyperstimulated and treated with GnRH-I agonist from the start of pregnant mare serum gonadotropin (PMSG) until the day of hCG (human chorionic gonadotropin) for 5 consecutive days. Blood and tissue samples were collected at 48 hours after hCG injection. VEGFA levels were evaluated in the peritoneal fluid by ELISA. Serum progesterone and estradiol were measured by RIA. Histological features of sectioned ovaries were assessed in hematoxilin and eosin stained slides. Cell proliferation and apoptosis were assessed by immunohistochemistry for PCNA and TUNEL, respectively. FLK-1 (VEGFA receptor) and PCNA protein levels were evaluated by western blot. In the OHSS model, treatment with GnRH-I agonist resulted in a significant decrease in ovarian weight as well as a decrease in progesterone and estradiol serum levels. Moreover, this agonist significantly decreased the concentration of peritoneal VEGF. GnRH-I agonist significantly decreased the number of development CLs and mature CLs in the OHSS group compared to the OHSS group without treatment. The treatment with GnRH-I agonist significantly decreased the levels of FLK-1 in the OHSS rats. GnRH-I agonist treatment reduced the diameter of CLs, as well as decreased CL cell proliferation in OHSS model. Finally, GnRH-I agonist increased apoptosis in CLs from OHSS group. In conclusion, in the OHSS model, the administration of GnRH-I agonist interferes with luteal steroidogenesis, angiogenesis and CL development associated with a decrease in luteal proliferation and an increase in apoptosis process. Therefore, the treatment with a GnRH-I agonist decreased the severity of OHSS in an immature rat model stimulated by PMSG/hCG. Supported by: Roemmers Foundation, CONICET (PIP 1223) and ANPCYT (PICT 2004/5-26047). (poster)

Antiovulatory and abortifacient effects of Areca catechu (betel nut) in female rats

Objectives:To study the antiovulatory and abortifacient effects of ethanolic extract of Areca catechu in female rats.Materials and Methods:For antiovulatory effect, ethanolic extract of A. catechu at 100 and 300 mg/kg doses was administered orally for 15 days. Vaginal smears were examined daily microscopically for estrus cycle. Rats were sacrificed on 16th day. Ovarian weight, cholesterol estimation, and histopathological studies were done. Abortifacient activity was studied in rats at 100 and 300 mg/kg doses administered orally from 6th to 15th day of pregnancy. Rats were laparotomised on 19th day. The number of implantation sites and live fetuses were observed in both horns of the uterus.Results:The extract of A. catechu showed a significant decrease in the duration of estrus at 100 mg/kg (P = 0.015) and 300 mg/kg doses (P = 0.002) as compared with control. Metestrus phase was also significantly reduced at 100 mg/kg (P = 0.024) and 300 mg/kg doses (P = 0.002). There was a significant increase in proestrus (P < 0.001) phase. However, diestrus phase was unchanged. Histopathological study of the ovaries showed mainly primordial, primary, and secondary follicles in the test groups as compared to control. There was also a significant (P = 0.002) decrease in ovarian weight and a significant (P = 0.021) increase in ovarian cholesterol level at 100 mg/kg dose. In the study to evaluate abortifacient effect, the mean percentage of abortion with 100 and 300 mg/kg doses were 75.5% and 72.22%, respectively, which was significantly (P = 0.008 and P = 0.006, respectively) increased when compared with control.Conclusion:The ethanolic extract of A. catechu at doses of 100 and 300 mg/kg has antiovulatory and abortifacient effects.

Genotoxicity of sodium arsenite and DNA fragmentation in ovarian cells of rat

Present study examined the genotoxic effects of arsenite in ovarian tissue of rat at 56 days of age. Immature (28 days old) female rats were exposed to different doses (50, 100, and 200 ppm) of sodium arsenite in drinking water for 28 days. DNA damage in ovarian tissue was measured by comet assay. All doses induced significant decrease in ovarian weight in a dose-dependent manner compared to control, more prominently at ( P < 0.001) 100 and 200 ppm. All the comet assay parameters showed significant difference with arsenite treatment compared to control group. In treatment groups, mean number of cells with intact DNA decreased while, mean comet number increased ( P < 0.001) in a dose-dependent manner compared to control. Significant decrease ( P < 0.05) was observed in mean comet length, height, comet head diameter and %DNA in comet head of high dose groups compared to control group. Dose dependent increase was found in mean comet tail length, %DNA in tail, tail moment and olive tail moment in high dose groups compared to control group. The study indicates that arsenic caused DNA damage to ovarian cells particularly at high doses and ensure comet assay as an effective method to detect DNA damage in tissue caused by metals.

Effects of Short and Long Term Treatment of Ballota undulate on Female Albino Rats Fertility and Pregnancy

The objectives of this study is to investigate the toxic effects of Ballota undulata (300 mg kg(-1) b.wt.) on the reproductive system after administration to female Sprague-Dawley rats for two time periods 4 and 12 weeks. Forty adult female Sprague-Dawley rats were divided into two treatment and two control groups of 10 rats each. The two treated groups received 15 mg kg(-1) b.wt. of Ballota undulata for two periods of 4 and 12 weeks. Female rats were allowed mating with males after treatment. Several pregnancy parameters were investigated including: total number of pregnant rats, body weight and reproductive organ weight, number of implantation sites, number of resorption sites and number of viable fetuses. The significance of these results was calculated using student's t and Chi-square tests. Exposure to Ballota undulata for 4 weeks did not have significant effects on most parameters investigated. However, a slight decrease in the relative ovarian and embryo weights was observed. Administration of Ballota undulata for 12 weeks significantly reduced the percentage of pregnancies and the number of implantation sites when compared with controls. In addition, a decrease in ovarian weights and in viable fetuses' number was also observed. Histological sections of ovaries of female treated with Ballota undulata were found to have congested blood vessels in cortical and medullary regions. We also noted the arrestment of developing follicles at primary and secondary stages in addition to presence of degenerative areas and hypercellullarity in medulla. Long term treatment with Ballota undulata might lead to diversified negative effects on fertility and pregnancy in female rats.

In Utero and Lactational Exposures to Low Doses of Polybrominated Diphenyl Ether-47 Alter the Reproductive System and Thyroid Gland of Female Rat Offspring

BackgroundPolybrominated diphenyl ethers (PBDEs) are capable of disrupting thyroid hormone homeostasis. PBDE-47 (2,2′,4,4′-tetrabromodiphenyl ether) is one of the most abundant congeners found in human breast adipose tissue and maternal milk samples.ObjectivesWe evaluated the effects of developmental exposure to low doses of PBDE-47 on the female reproductive system.MethodsPregnant Wistar rats were administered vehicle (peanut oil) or PBDE-47 [140 or 700 μg/kg body weight (bw)] on gestation day (GD) 6, or 5 mg 6-n-propyl-2-thiouracil (PTU)/L in the drinking water from GD7 through postnatal day (PND) 21.ResultsIn female offspring sacrificed on PND38, there was a significant decrease in ovarian weight after exposure to PTU or 140 μg/kg PBDE-47. Alterations in folliculogenesis were apparent: we observed a decrease in tertiary follicles and serum estradiol concentrations in the offspring exposed to either PTU or 700 μg/kg PBDE-47. PTU exposure also resulted in a decrease in primordial follicles. On PND100, persistent effects on the thyroid glands included histologic and morphometric changes after exposure to either PTU or PBDE-47. No relevant changes in reproductive indices were observed after mating the exposed F1 females with nontreated males.ConclusionsAdministration of PBDE-47 at doses relevant to human exposure led to changes in the rat female reproductive system and thyroid gland.

Short and Long Effects of Citrullus colocynthis L. on Reproductive System and Fertility in Female Spague-Dawley Rats

Aim of this study is to investigate the toxic effects of Citrullus colocynthis L. (400 mg/kg/body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and Citrullus colocynthis L. were intraperitoneally injected to experimental animals in dose of 400 mg/kg/body wight. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using students t and Chi-square tests. The effect of Citrullus colocynthis L. exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Citrullus colocynthis L. for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Citrullus colocynthis L. were observed. Exposure to Citrullus colocynthis L. for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed a decrease in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Citrullus colocynthis L. causes adverse effects on the reproductive system and fertility.

Subchronic and chronic safety studies with genistein in dogs

Genistein is a phytoestrogen that occurs naturally in the diet, especially in soy-based foods. There is widespread interest in phytoestrogens as chemopreventive agents for a variety of diseases and cancers based on epidemiologic evidence. Although soy and its constituents, such as genistein, have been consumed at high levels in several Asian populations without apparent adverse effects, concern has been raised about potential adverse effects due to estrogenic and other activities. The subchronic and chronic safety of genistein were evaluated in the beagle dog including a 4-week study and a 52-week safety study with a 13 week interim sacrifice and a 4 week recovery period. In both studies at doses of 50, 150 and 500 mg/kg/day, genistein was well tolerated. In the 4 week study, except for an increase in uterine weights in female dogs at 500 mg/kg/day, there were no other treatment related findings. In the 52-week study, the primary effects of genistein were observed on the reproductive tract, which included for male dogs: reduced size and/or weight of the testes, epididymus and prostate of 2/2 dogs after 13 weeks of treatment and in 1/4 dogs after 52 weeks of treatment at 500 mg/kg/day. The histological changes observed in the affected dogs at 500 mg/kg/day indicated atrophy of the testes and prostate gland and absent spermatozoa in the epididymus. At the mid-dose of 150 mg/kg/day, although there was a reduction to a lesser extent in testes weight after 13, but not 52 weeks, there were no histopathological changes. In female dogs, the reproductive tract effects included increased uterine weight at 500 mg/kg/day after 13 weeks of treatment, but not after 52 weeks of treatment. There was also a small decrease in ovarian weights at 150 and 500 mg/kg/day after 13 weeks and at 500 mg/kg/day after 52 weeks of treatment. There were no histopathological correlates to the changes in organ weights in female dogs. In the 4-week recovery group dogs, no changes were observed in dogs previously treated for 52 weeks with 500 mg/kg/day of genistein. It is concluded that the administration of genistein to dogs for a period of 4–52 weeks was well tolerated and did not result in systemic toxicity. Effects of genistein on the reproductive tract at very high doses were functional in nature and are of a type that would be expected in view of the relatively weak estrogenic activity of genistein and were considered not adverse effects. In the 4-week study, the no observed adverse effect level (NOAEL) for genistein was considered to be >500 mg/kg/day and the no observed effect level (NOEL) was considered to be 150 mg/kg/day. For the 52-week study, the NOAEL is considered to be >500 mg/kg/day and the NOEL is considered to be 50 mg/kg/day.

Effects of pentoxifylline in the prevention of ovarian hyperstimulation syndrome in a rabbit model

Tumor necrosis factor α (TNF-α) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-α synthesis. The aim of this study was to evaluate whether the use of petoxifylline would prevent the occurrence of OHSS in a rabbit model. Thirteen rabbits were divided into two groups. The first group (n = 6) were given pentoxifylline 15 mg/kg intravenously and the second group (n = 7) were given physiological serum 15 mg/kg before ovulation induction. Ovarian hyperstimulation was induced in rabbits by 200 IU equine chorionic gonadotropin on day 1 and 100 IU human chorionic gonadotropin on day 3. Blood samples were analyzed for TNF-α on days 1, 3 and 5. All animals were autopsied on day 6 to evaluate the ovarian weight, ascites formation and histopathological changes. There was no difference between groups regarding weight gain, ascites formation and plasma TNF-α levels (p > 0.05). Ovarian weight and number of ovulations were significantly lower in the pentoxifylline group than the control group (p < 0.05). Pentoxifylline did not prevent ascites formation despite the observed decrease in ovarian weight and number of ovulations in OHSS in a rabbit model.

Effect of dimethoate administration schedules on compensatory ovarian hypertrophy, follicular dynamics, and estrous cycle in hemicastrated mice.

Dimethoate, a widely used organophosphate insecticide, was administered orally (28 mg/kg body weight) to hemicastrated (HC) virgin mice on day 1 and for 5, 10, and 15 days. Hemicastrated untreated control mice showed a significant increase in relative ovarian weight, with 42.74% hypertrophy and an increase in healthy and atretic follicles when compared with those of sham-operated control animals. The HC mice treated for 1 day or for 5 days showed no significant change in ovarian weight (36.64% and 25.19% hypertrophy, respectively) or in healthy and atretic follicles, when compared with HC-control mice. Treatment with dimethoate for 10 or 15 days, however, resulted in a significant decrease in ovarian weight (19.84% and 0.76% hypertrophy, respectively), a significant decrease in the number of healthy follicles, and a concomitant significant increase in the number of atretic follicles when compared with those in HC control animals. No significant change occurred in the number of estrous cycles or duration of each phase of the estrous cycle in HC mice treated with dimethoate for either 1 or 5 days. In HC mice treated with dimethoate for 10 or 15 days, however, a significant decrease in the number of estrous cycles, duration of proestrus, estrus, and metestrus, a concomitant significant increase in the diestrus phase, when compared with HC control animals. In mice receiving dimethoate for 15 days (but not for 1, 5, or 10 days) a significant decrease occurred in body weight and in the weights of the uterus, kidney, spleen, and liver when compared with the parallel weights in HC control animals. The overall findings suggest that following dimethoate treatment, a significant decrease in ovarian weight with a concomitant increase in compensatory ovarian hypertrophy and in the number of healthy follicles, with a concomitant increase in the number of atretic follicles and interrupted estrous cycles, may be due to the direct effect on the ovary or may be due to a hormonal imbalance in any stage of the hypothalamo-hypophysial ovarian axis.

Effects of pentoxifylline in the prevention of ovarian hyperstimulation syndrome in a rabbit model

Tumor necrosis factor α (TNF-α) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was foundto inhibit TNF-α synthesis. The aim of this study was to evaluate whether the use of petoxifylline would prevent the occurrence of OHSS in a rabbit model. Thirteen rabbits were divided into two groups.The first group (n = 6) were given pentoxifylline 15 mg/kg intravenously and the second group (n = 7) were given physiological serum 15 mg/kg before ovulation induction. Ovarian hyperstimulationwas induced in rabbits by 200 IU equine chorionic gonadotropin on day 1 and 100 IU human chorionic gonadotropin on day 3. Blood samples were analyzed for TNF-α on days 1, 3 and 5. All animals wereautopsied on day 6 to evaluate the ovarian weight, ascites formation and histopathological changes. There was no difference between groups regarding weight gain, ascites formation and plasma TNF-αlevels (p > 0.05). Ovarian weight and number of ovulations were significantly lower in the pentoxifylline group than the control group (p < 0.05). Pentoxifylline did not prevent ascitesformation despite the observed decrease in ovarian weight and number of ovulations in OHSS in a rabbit model.

Inhalation toxicology of octamethylcyclotetrasiloxane (D4) following a 3-month nose-only exposure in Fischer 344 rats.

Octamethylcyclotetrasiloxane (D4) is a low-molecular-weight cyclic siloxane used primarily in the synthesis of silicone polymers. The objective of the present study was to evaluate the subchronic toxicity of D4 following a 3-month nose-only inhalation exposure. Male and female Fischer 344 rats (20/sex/group) were exposed 6 h/day, 5 days/week for 3 months to vapor concentrations of 0, 35, 122, 488, and 898 ppm D4. Also, an additional 10 per sex in the control and high-exposure groups were allowed a 4-week recovery period to observe reversibility, persistence, or delayed occurrence of any potential adverse effects. Body weights and food consumption were monitored at least twice weekly over the course of exposures. Approximately 18 hours preceding euthanasia, animals were transferred into metabolism cages for urine collection, and were fasted. At necropsy, rats were anesthetized with pentobarbital and euthanized by exsanguination. Blood was collected for hematological and clinical biochemical analyses. Selected organ weights were measured and a complete set of tissues was taken for histopathological examination. A concentration-dependent increase in absolute and relative liver weight (488 to 898 ppm) and a significant decrease in ovarian weight (898 ppm) were observed in female rats. Exposure to D4 via nose-only inhalation (35 to 898 ppm) produced minor alterations in hematological and serum chemistry parameters that were considered either incidental and of little toxicological significance (hematology) or suggestive of metabolic adaptation/alteration (serum chemistry) in response to exposure-related hepatomegaly. There were no histopathological findings noted in the liver. Histopathological evidence indicated the primary target organs following D4 inhalation exposure to be components of the female reproductive tract. Reversible histopathological changes were observed in the ovary (hypoactivity) and vagina (mucification) of female rats in the high-dose group only (898 ppm). Although an increase in the incidence and severity of both macrophage accumulation, interstitial inflammation, and eosinophil infiltration was observed in the lungs of male and female rats exposed to D4, the toxicological significance is uncertain as other inhalation studies at similar concentrations failed to show these effects. In summary, nose-only inhalation of a high concentration of D4 resulted in reversible histopathological changes in the female rat reproductive tract. Lower concentrations did not elicit these same effects.

A Novel Melatonin Antagonist, N-(2,4-Dinitrophenyl)-5-Methoxytryptamine Neutralizes Some Effects of Melatonin in the Female Syrian Hamster

In this present study we evaluated the ability of a recently synthesized melatonin antagonist, N-(2,4-dinitrophenyl)-5-methoxytryptamine (ML-23), to antagonize the effects of afternoon injections of melatonin on the reproductive and thyroid axes in the female Syrian hamster. Thirty-six animals were divided into four groups and treated daily for 13 weeks with an afternoon injection of melatonin (25 micrograms/injection) or saline diluent. ML-23 was given via the drinking water to both melatonin- and saline-treated groups. The experiment was continued until 78% of melatonin-treated animals exhibited acyclicity. The results show that ML-23 partially reversed the effects of melatonin on pituitary follicle-stimulating hormone concentrations but was without effect on the decreased pituitary and plasma prolactin concentrations induced by melatonin treatment. Furthermore, ML-23 antagonized the effects of melatonin on plasma thyroxine levels and significantly increased plasma triiodothyronine concentrations and the free triiodothyronine index when used in combination with melatonin. The decrease in ovarian weight and plasma estradiol, but not progesterone, obtained with melatonin treatment also was reversed by ML-23. Our data suggest that ML-23 prevents the effects of melatonin treatment on ovarian weight, pituitary follicle-stimulating hormone levels, plasma estradiol, and thyroxine concentrations in the female Syrian hamster. Since ML-23 did not prevent the effects of melatonin on pituitary weight, plasma luteinizing hormone and prolactin, and pituitary prolactin concentrations, the actions of ML-23 may involve only peripheral sites of action of melatonin. Alternatively, the dose of ML-23 may not have been optimal to prevent all of the central effects of the indoleamine.

Ovarian damage to Channa punctatus after chronic exposure to low concentrations of elsan, mercury, and ammonia

Histopathological changes were induced in the ovary by chronic nonlethal levels of Elsan (211 ppb), mercury (16.7 ppb), and ammonia (15.64 ppm). In the breeding season, treated Channa punctatus revealed a significant decrease in ovarian weight throughout the duration of the experiment. Acute changes were noted in the diameter and percentage occurrence of the different stages of oocytes. In all cases, stage I oocytes revealed no difference in diameter with respect to control although they demonstrated an increase in the percentage occurrence. For stages II and III, a remarkable decrease occurred in both the number and the diameter of these mature oocytes. The preponderance of stage I and destruction of stage II and stage III oocytes in all three treatments indicate that chemically diverse xenobiotics have equal reproductive toxicity in fish, interfering with their breeding.

A new irreversible aromatase inhibitor, 6-methylenandrosta-1,4-diene-3,17-dione (FCE 24304): antitumor activity and endocrine effects in rats with DMBA-induced mammary tumors

The antitumor activity of the new irreversible aromatase inhibitor 6-methylenandrosta-1,4-diene-3,17-dione (FCE 24304) was studied in rats with 7,12-dimethylbenzanthracene (DMBA)-induced tumors; several endocrine parameters were evaluated in these animals. The compound was given s.c. and p.o. twice daily, 6 days/week, for 4 weeks. The control group showed 13% tumor regression (0% complete remission, CR; 13% partial remission, PR). FCE 24304 given s.c. induced 44% (22 + 22) regressions at the dose of 3 mg/kg per day, 70% (40 + 30) at 10 mg/kg per day, 73% (27 + 46) at 30 mg/kg per day, and 70% (50 + 20) at 100 mg/kg per day. FCE 24304 given orally induced 25% (17 + 8) tumor regressions at 30 mg/kg per day and 50% (17 + 33) at 100 mg/kg per day. Rats were killed 4 h after the last dose and the aromatase activity of ovarian microsomes (OAA) was evaluated. OAA was reduced by 56% after s.c. treatment with 3 mg/kg per day FCE 24304; complete OAA suppression (greater than or equal to 96%) was obtained starting at 10 mg/kg per day s.c. Oral treatment slightly reduced OAA only at a dose of 100 mg/kg per day (36%). Body weight increased in all the groups s.c. treated with FCE 24304 but not in those treated orally. The weights of the pituitary, adrenals, and uterus were reduced in rats treated s.c. with 10 and 30 mg/kg per day; at 100 mg/kg per day, a decrease in ovarian weight was observed while uterus weight was similar to that of controls. Oral FCE 24304 increased ovarian weight at a dose of 30 mg/kg per day but not at 100 mg/kg per day. Serum prolactin (PRL) and luteinizing hormone (LH) levels did not change. In conclusion, FCE 24304 given s.c. proved highly effective against DMBA-induced tumors in rats but had less activity when given orally. Its intrinsic androgenic activity, higher after s.c. than after oral treatment, could contribute to the antitumor effect in the intact (premenopausal) rat model.

N-(2,4-dinitrophenyl)-5-methoxytryptamine, a novel melatonin antagonist: effects on sexual maturation of the male and female rat and on oestrous cycles of the female rat [corrected

N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] has recently been synthesized and shown to antagonize the inhibitory effect of melatonin on the release of dopamine in vitro from the hypothalamus of female rats. In the present study the ability of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] to inhibit in vivo the following melatonin-mediated effects was investigated: (1) delayed sexual maturation of young male rats, (2) delayed sexual maturation of young female rats, (3) inhibition of ovulation in mature female rats and (4) re-establishment of oestrous cycles in adult female rats maintained in continuous light. The inhibitory effect of daily melatonin injections, given in the afternoon, on the growth of the prostate gland and seminal vesicles and on serum testosterone concentrations in young male rats was prevented by daily injections of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected]. Daily injections of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] alone did not affect sexual maturation of young rats. In young male rats treated through the drinking water with melatonin, the growth of the accessory sex organs, but not that of the testes, was delayed and serum concentrations of testosterone were lower than in untreated rats. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water increased serum concentrations of testosterone but did not significantly affect the weights of the accessory sex organs. Simultaneous administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] and melatonin through the drinking water prevented completely, in a dose-dependent manner, the melatonin-mediated decrease in epididymal weights and in serum concentrations of testosterone and partially inhibited the delayed growth of the prostate glands and seminal vesicles. In young female rats treated with melatonin through the drinking water for 30 days, the growth of the ovaries was inhibited and serum concentrations of oestradiol were lower than in untreated rats. The growth of the uterus was not significantly affected. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water did not significantly affect uterine and ovarian weights or oestradiol concentrations. Simultaneous administration of melatonin and N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water prevented completely the melatonin-mediated decrease in ovarian weights and in serum oestradiol concentrations. Ovulation during presumptive oestrus was prevented in adult female rats treated through the drinking water for 7 days with melatonin. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] alone did not significantly affect the average numbers of ova shed and corpora lutea present. Simultaneous administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] and melatonin prevented completely the melatonin-mediated inhibition of ovulation; the average number of ova shed was the same as in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Photoperiodic sensitivity of prepubertal female Fisher 344 rats.

The laboratory rat is thought to be a poor model for study of the photoperiodic control of reproduction; however, this has only been investigated in a few rat strains. The purpose of the present investigation was to determine if the neuroendocrine-reproductive system of the Fisher 344 (F344) rat, an inbred strain, is sensitive to light deprivation. All treatments were performed on 28-day-old female F344 rats and the animals maintained for 8 weeks in a 14:10 light:dark cycle. Blinding resulted in a 65% (P less than 0.01) reduction in uterine weight and a 25% (P less than 0.01) decrease in ovarian weight. Accompanying these reductions in blinded animals were significant inhibitions of anterior pituitary weight, serum prolactin levels, and pituitary prolactin synthesis as measured in vitro. Pinealectomy of the blinded animals prevented all of these effects. Additionally, when olfactory bulbectomy, a procedure known to sensitize rats to the effects of photoperiod, was combined with blinding, the results did not differ significantly from that found with blinding alone. From these data we conclude that 1) the neuroendocrine-reproductive system of the prepubertal F344 female rat is highly sensitive to light deprivation; 2) light deprivation produces its antigonadotrophic effect through the pineal gland; and 3) olfactory bulbectomy does not potentiate the effects of blinding in the F344 rat.

A possible mechanism of rapid luteolysis in white-footed mice, Peromyscus leucopus.

Adult female white-footed mice, Peromyscus leucopus, were exposed to long (LP) or short (SP) photoperiods for 6 weeks (experiment I). Another group of animals was kept for 6 weeks in SP, then injected SC with 30 micrograms prolactin twice daily for 2, 3, 4, or 6 days (experiment II). Ovaries from the mice in both experiments were weighed and serially sectioned for light microscopic examination of regressing corpora lutea. In experiment I, it was observed that vessels supporting corpora lutea were dilated, and that their endothelium was either undergoing necrosis or it was missing. Pronounced changes of luteal capillaries led to rupture and intraluteal hemorrhage, thus opening the capillary bed. Regressing luteal cells became segregated and seemed to invade the vascular system passively. They were seen as luteal cell thrombi in medullary veins. This luteolytic course termed "rapid luteolysis" was most apparent in SP ovaries. It differed from "retarded luteolysis," which represents the well-established luteolytic model of auto- and heterophagocytosis. In experiment II, there was a statistically significant decrease in ovarian weight 4 days after prolactin treatment in comparison with saline-treated controls. At the light microscopic level, signs of both rapid and retarded luteolysis were present, but not intensified. It is concluded: (1) The concept of rapid luteolysis represents a reasonable working hypothesis. (2) Prolactin, though luteolytic at the macroscopic level, failed to produce evidence of increased rapid or retarded luteolysis at the light microscopic level.

The role of gonadotropins in the development of cyclicity in the rat.

Two experiments were carried out to determine whether the serum gonadotropin levels found in the neonatal female rat play a role in the sexual differentiation of the neuroendocrine axis. Female rats were injected either with 100 μg of testosterone propionate (TP) on day 2 or day 3, or with the combination of TP and gonadotropins (5O μg of FSH and 5O μg of LH/day for 3 days). When animals receiving both gonadotropins and TP were compared with those receiving TP alone, it was observed that gonadotropins significantly delayed or prevented the onset of persistent vaginal estrus (p < 0.01) and significantly ameliorated both the decrease in ovarian weight (p < 0.05) and the loss of female sexual behavior (p < 0.05) due to the injection of testosterone propionate. The possible sites of action for the gonadotropins and a hypothesis for the mechanism of action are discussed. (Endocrinology 92: 500, 1973)