adverse effects of methoxsalen on the oogenesis of Balb/C mice

Methoxsalen is a natural photoactive compound which is found in many seed plants. A number of epidermal proliferative disorders can be treated by methoxsalen along with long wave ultraviolet A [UVA]. In an experimental study, we aimed to demonstrate the effect of methoxsalen, UVA and their combination on oogenesis Balb/C mice. There were two experimental groups and a control group. The experimental groups were composed of i. a short term group with treatment duration of 15 days and ii. a long term group with treatment duration of 5 weeks. Both the long term and short term experimental groups were further subdivided into a UVA group, a methoxsalen group and a methoxsalen plus UVA group. After treatment, mature females in prosterus phase of ovarian cycle were scarified with ether, while their ovaries were removed and prepared for histological studies. Both macro and microscopic studies showed significant anomalies [p<0.05] among experimental group ovaries as compared to control group. The obtained results showed a significant decrease in the following factors: number and diameter of corpus lutei, Graafian follicles, diameter of granulosa cell layer and oocytes, number of primordial primary and growing follicles, while we observed an increase in number of atretic follicle. Furthermore, our findings confirmed an increase in theca diameter only through UVA treatment. Methoxsalen also reduced circulating estrogen levels in blood serum, significantly. Other cases of teratogenecity, such as follicles with three oocytes and disorganization in corpus luteum cells were observed. The result suggests that UVA, methoxsalen and their combination cause health problems and cell injuries

Melatonin impact on in vitro development of mouse preantral follicles and oocyte maturation

Melatonin acts as an indirect antioxidant and is a powerful direct free radical scavenger and direct responses to melatonin in the gonads are detected. This study aims to investigate the influence of different doses of melatonin on preantral follicle development and oogenesis of in vitro cultured mouse ovarian follicles. Preantral follicles with diameters of 150- 175 micro m were mechanically isolated from NMRI mouse ovaries. Follicles were cultured in droplets of alpha-minimal essential medium [alpha-MEM] supplemented with 5% FBS, 100 mIU/ml rhFSH, 1%ITS, 100 IU/ml penicillin and 100 micro g/ml streptomycin in conjunction with varying doses of melatonin [0, 1, 10, 100 nM and 100, 500 pM] for six days. On day six, in vitro ovulation was induced by the addition of hCG/rEGF to the culture medium and after 16-20 h the maturation state of the oocytes was assessed. There was a significant [P<0.05] decrease in the number of surviving follicles in the groups that received 10, 100 nM and 500 pM melatonin compared to the other groups. After induction of in vitro ovulation, follicles in groups that received 1, 10, and 100 nM melatonin had higher ovulation rates [P<0.05] compared with the other groups. Oocyte maturation capacity was adversely influenced by five concentrations of melatonin and GV arrest was significantly higher compared to the control group [P<0.01]. Our data indicates that a dose of 100 pM melatonin has no toxic effects on follicular development and can be used to reduce oxidative stress in follicle culture systems

Effect of imatinib on the oogenesis and pituitary -ovary hormonal axis in female wistar rat

Imatinib mesylate, a small-molecular analog of adenosine triphosphate [ATP] that potently inhibits tyrosine kinase activities of Bcr-Abl, PDGFR-beta, PDGFR-alpha, c-Fms, Arg and c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy. We tested the effect of imatinib on the ovarian histological structure and the concentration of estrogen and progesterone, luteinizing hormone [LH] and follicle stimulating hormone [FSH] in the serum of female Wistar rats. Two groups of rats [180 +/- 15 grains] were gavaged with doses of 50 and 100 mg/kg body weight imatinib dissolved in distilled water for 14 days. The control group received sterile water. On day 7, after termination of the treatment, blood serum concentration was measured with the radioimmunoassay [RIA] method. Also, sections [5 micro m thick] of ovaries stained with hematoxylin and eosin [H and E] were investigated histologically. Progesterone concentration in the experimental groups was increased [p<0.001], estrogen and FSH concentrations were decreased [p<0.01], and the LH concentration decreased but was not statistically different in comparison with the control group. The weight of ovaries and number of atretic follicles in the experimental groups was increased compared with the control group [p<0.05]. The diameter of corpus lutea were increased but the number of corpus lutea decreased in both experimental groups [p<0.01]. These findings suggest that administration of imatinib may have profound effects on female fertility

[ effects of sodium benzoate [C[6]h[5]COONa] on ovaries and its hormones and gonadotropins on female balb/C mice]

Sodium benzoate [C[6]H[5]COONa] is used as a disinfectant against microorganisms existing in healthy foods and drugs. The aim of this study was to determine the effect of sodium benzoate on ovaries and its hormones and gonadotrophins on balb/C mice. Eighteen adult female mice [balb/c] were divided into 3 groups of 6 animals each. Two groups of animals were treated with 280 or 560mg/kg/day sodium benzoate for 60 days [Group II and III, respectively]. Animals of group I were administrated water without sodium benzoate for 60 days and served as the controls. On the 61st between 08:00 to 10:00, blood samples were collected from the left ventricle after anesthesia with diethyl ether. After that the mice were killed following ethical procedure, the ovaries were dissected out, then, it was immediately fixed in formalin 10% and embedded in paraffin. Sections of 5 micro m thickness were taken from the mid portion of each ovary. Plasma levels of FSH and LH were significantly decreased in group III compared to control group [P<0.0001]. Plasma level of progesterone was significantly decreased in treatment groups compared to control group [P<0.001]. Decrease of oogenes and disorganization of ovaries in electron microscopy investigation determined. The results of present study indicate that sodium benzoate affect and decrease the oogenesis and reduce of follicles and corpus luteum. Thus, it is suggested to replace it if necessity

[70-day supraphysiologic dose of the power-enhancing drug oxymetholone: the effects on oogenesis in NMRI mice]

Oxymetholone is an orally-administered active anabolic-androgenic steroid. This drug was synthesized in 1959. It is a 17alpha-methylated, 5alpha-saturated compound. It is used for the treatment of a variety of diseases including anemia, growth delay in children, myocardial damage in heart failure and treatment of HIV associated wasting. This is one of the drugs used in high doses by the doping athletes because of its anabolic effects and its influence on muscular mass. In this study, the effect of oxymetholone in supraphysiologic doses was evaluated on oogenesis in NMRI mice. In our experiments, 12 mg/kg/day oxymetholone was injected intraperitoneally to 4- and 6-week old mice for 70 days. The results demonstrated a significant difference between treatment and control groups after both 35 and 70 days of treatment. This drug led to significant decrease in the number of corpus lutea, decrease in the number of atretic follicles, decrease in the weight and diameter of ovaries, decrease in the diameter of granulosa layer, increase in number of primordial follicles, decrease in number of primary follicles, decrease in number of growing follicles, decrease in the number of graafian follicles, and decrease in the progesterone level. Additionally, disordered formation of granulosa layers and growing of oocytes in antra, anomaly of the ovular medulla and formation of two oocytes in one folliculus were observed in some mice. The results show that oxymetholone decreases the ovarian growth and the rate of ovulation

Ovarian monosaccharides (glucose and fructose): hormonal effects and their role in final oocyte maturation and egg quality in catfish Heteropneustes fossilis, Bloch.

In the catfish H. fossilis, ovarian glucose and fructose levels showed significant annual variations that could be correlated with the gonado-somatic index. The concentration of the sugars, which was low in resting phase of gonad increased with the onset of oogenesis, reaching the peak in prespawning (June) phase. Glucose is the predominant monosaccharide in the late oogenesis, while fructose in early oogenesis and resting phase. Administration of a single injection of HCG (100 IU/fish) decreased glucose at 4 hr but increased fructose (6 hr) in the resting phase. In the preparatory phase (active oogenesis), fructose decreased significantly at 4 hr and glucose at 6 and 12 hr. In the prespawning phase, HCG administration induced a significant decrease in glucose level at 2 hr but increased it significantly at 16 and 18 hr. Fructose concentration, on the other hand, decreased > or = 4 hr. The involvement of different energy substrates (glucose, fructose, 2-deoxyglucose and pyruvate) on final oocyte maturation and viability of eggs were demonstrated in an in vitro study, employing incubation of mature oocytes in medium containing one or the other energy substrates. Glucose at 4 and 8 mM concentrations increased the viability of eggs without affecting germinal vesicle break down (GVBD) and at high concentrations (16 and 32 mM) marginally increased GVBD but decreased viability. Pyruvate at high concentrations (> or = 8 mM) produced a positive effect on both GVBD and viability. Fructose and 2-deoxyglucose did not elicit any effect on these parameters. The results suggest that glucose has an active role in catfish oogenesis and maintaining egg quality and HCG influences monosaccharide metabolism in a season-dependent manner.

First ovarian maturity and recovery response in common carp, Cyprinus carpio after exposure to carbofuran.

The present study embodies the observations on duration (45, 75 and 105 days) dependent effects of toxicologically low concentration (16 ppm) of a carbamate pesticide, carbofuran, on first ovarian maturity with correlative recovery response by withdrawal of treatment for 30 days in virgin yearlings of common carp, Cyprinus carpio var. Communis. In control fish histological organization of ovary and changes in gonado-somatic index (GSI) revealed the initiation of oocyte differentiation and development at the commencement of experiment in December-January and peak of maturation with fully grown yolky oocytes was attained by the time of termination of experiment in the end of March. In carbofuran exposed groups ovaries exhibited retardation of development and growth evident by significantly decreased GSI and predominace of immature oocytes passing through nuclear-cytoplasmic degeneration of variable magnitude. Severity of degenerative changes was more pronounced with prolonged duration. In recovery group ovaries had experienced regeneration as clued by the presence of oocytes of differential stages including vitellogenic and fully grown oocytes. In liver histopathological changes coupled with significant decrease in hepato-somatic index (HSI) attributed hepatic inactivation in all exposure groups whereas in recovery group an increase in HSI value with marked sign of hepatic reactivation was evidenced. No significant change in values of condition (CF) and somatic condition (SCF) factors substantiated the over all normal health of fish. Lipid and water content of ovary, liver and muscle registered the significant decrease at 105th day of exposure with concomitant augmented value for recovery group. These observations suggest that the commercial formulation of carbofuran, even at this toxicologically low concentration, is equally capable of affecting the first ovarian maturity with associated physiological implications but with reversibility in toxicity by withdrawal of pesticide exposure attributing regeneration in affected organs in due course time.

Effect of mercury and methyl parathion on the ovaries of Labeo rohita (Ham).

Adult pre-spawning fish Labeo rohita were sublethally (1/5th 96h LC50) exposed to mercuric chloride and metacid-50 (methyl parathion). Accumulation of mercury and methyl parathion was studied and it was found that pre-spawning ovary appears as a potent organ for deposition of both the pollutants. RNA/DNA ratio of the control and treated fish were studied. It was found that the signifcant decrease in RNA/DNA ratio occurs after 9 and 30 days of exposure for mercury and 30 days for methyl parathion. Fluorescence microscopic studies by acridine orange staining method were also performed to show how much it is related to biochemical alterations. In some cases loss of metachromasia is correlated with the fall in RNA/DNA ratio. Some other abnormalities like fall in stage II: stage I oocyte ratio and necrosis was also observed.

Inhibitory effect of 1-benzyl-5[(C)-2,6-dimethyl-1,5-heptadienyl] imidazole (KK-42) on desert locust, Schistocerca gregaria forsk.

Imidazole compound KK-42 was tested for its inhibitory effect on Schistocerca gregaria. The compound caused 80% mortality after 19 days of treatment with 100 microg of KK-42/insect. It also caused the production of deformed adults at even lower doses. Ecdysteroid content, when estimated by RIA, declined due to KK-42 treatment in both haemolymph and ovaries of the insect. Reduction in ecdysteroid titer was maximum at 100 microg of KK-42/insect. The value estimated by RIA was 0.34 ng/pL haemolymph as compared to 0.97 ng/microL in case of controls. Similarly,ecdysteroid content of ovaries detected was 0.48 ng/mg in treated ones as compared to 0.61 ng/mg in controls. Histological studies, however, revealed no alteration in the ovarian tissues due to KK-42 treatment.

Carbofuran induced impairment in the hypothalamo-neurohypophyseal-gonadal complex in the teleost, Channa punctalus (Bloch).

The effect of chronic exposure to carbofuran (4.5 ppm in static water) for six months on the gonadal histophysiology and hypothalamo-neurohypophyseal complex was studied in Channa punctatus. Experimental observations revealed significant inhibition of gonadal development with associated degenerative abnormalities as evidenced by ovarian and testicular histology and reduced gonadosomatic index. Degenerative changes in ovary were exihibited by stage I (oogonium) and stage II (immature/non-vitellogenic) oocytes as marked by perinuclear ooplasmic lysis, clumping and dissolution resulting in disintigration of nuclear material altogether attributed to complete degeneration of such oocytes. Testicular deleterious changes included degeneration of spermatogenic elements and necrosis of interstitial cells of Leydig. Correlative histophysiological changes were also observed in the pituitary gonadotrophs and hypothalamic, nucleus pre-opticus, neurons that were smaller, inactive and less in number with associated necrosis. Corresponding to the changes in nucleus pre-opticus neurons, significant inhibition of brain monoamine oxidase enzyme activity was also recorded in treated group. These observations suggest that carbofuran even at low concentration level under long-term exposure is capable of inducing retardation of gonadal development which might have been mediated through the impairment of the hypothalamo-neurohypophyseal-gonadal axis in this species.

Short-and long-term effects of proallatotoxin (ethoxyprecocene II) on Rhodnius prolixus females

A ovogênese e a postura de ovos pode ser inibida, durante o primeiro ciclo reprodutivo de Rhodnius prolixus, por um único tratamento com etoxiprecoceno II. Esta inibiçäo, se medida pelo crescimento dos ovócitos, maturaçäo de ovos e ovipostura, depende da dose do composto utilizado. A produçäo de ovos, no entanto, pode ser parcial ou totalmente restabelecida após dois subseqüentes repastos de sangue sem a droga. Estes dados sugerem que a açäo do etoxiprecoceno II sobre o corpus allatum näo é irreversível em fêmeas de Rhodnius prolixus