Relative Ovarian Weight Research Articles

Triptolide induces adverse effect on reproductive parameters of female Sprague-Dawley rats

The aim of this study was to investigate the adverse effects of triptolide, a diterpenoid triepoxid and a major active component isolated from Triptergium wilfordii Hook.f (TWHF), on various reproductive parameters of female Sprague-Dawley (SD) rats. Female SD rats were treated with triptolide by oral administration (gastric infusion; 0, 100, 200, and 400 μg/kg) once-daily for 90 days. During the experimental period, vaginal smears were taken to monitor the estrous phase for the last 30 days. Relative ovary and uterus weights to body and histopathologically changes were determined on the last day. Serum levels of estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were assessed by enzyme immunoassay. ERα expression in the uterus and ovaries were analyzed from using immunohistochemical detection. The results showed that treatment with 200 and 400 ug/kg of triptolide significantly reduced serum levels of E2 and P and increased levels of FSH and LH. At these dose levels, relative weights of ovary and uterus were significantly reduced. Qualitative histological analysis of the ovaries revealed a reduction in developing follicles and increase in atretic follicles in treated animals. Further, estrous cycles were prolonged significantly. The expression of ERα in ovaries and the uterus decreased in treated animals. These data suggest that triptolide had a direct effect on the ovaries, and the decrease in steroids elicited feedback on FSH and LH. Thus, reduced levels of E2 and P may affect follicular development, estrous cycle, and expression of ERα.

Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague–Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate

The aim of the present study was to determine the ovotoxicity of female Sprague–Dawley (SD) rats exposed to benzo[a]pyrene (B[a]P) and di-(2-ethylhexyl) phthalate (DEHP), either alone or in combination; the molecular mechanism and the combined effects were also evaluated. Female rats were given intragastric administration of control (corn oil), B[a]P (5 and 10 mg/kg), DEHP (300 and 600 mg/kg) and B[a]P + DEHP (at 5 mg/kg and 300 mg/kg respectively, or at 10 mg/kg and 600 mg/kg respectively) on alternate days for 60 days. Relative ovary weight, estrous cycle, 17β-estradiol blood level, ovarian follicle populations, granulosa cell apoptosis, and gene and protein expression of P450Arom and PPAR were investigated. Our study demonstrated that the combination of B[a]P and DEHP exerts ovotoxicity in female rats and suppression of sex hormone secretion and homeostasis, which is associated with prolonged estrous cycles, decreases in ovarian follicle populations and granulosa cell apoptosis involving a PPAR-mediated signaling pathway of action of the two chemicals. In addition, based on qualitative assessment of the combined toxicity, no interaction effects were observed following combined B[a]P and DEHP administration.

Evaluation of embryotoxic potential of olaquindox and vitamin a in micromass culture and in rats.

Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg) , and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from 6th to 16th of pregnancy. IC50 values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and 28.32 μg/ml and 79.34 and 23.29 μg/ml in LB cell and those values of vitamin A were 8.13 and 5.94 μg/ml in CNS cell and 0.81 and 0.05 μg/ml in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1) , cranioarchschisis (14) , exencephaly (14) , dome shaped head (22) , anophthalmia (15) , brcahynathia (10) and others (19) . Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61) , defect of palatine bone (52/61) and others (50/61) . In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.

Evaluation of ovotoxicity in female mice caused by organic extracts in tap water from Jialing River in Chongqing, China

Recently, toxic effects of widespread organic pollutants have received much attention due to the hazards they pose to female reproductive health. The aim of the present study was to determine the female reproductive toxicity of organic extracts (OE) in tap water from the Jialing River in Chongqing, China. In our experiment, Kunming female mice that exhibited normal estrous cycles were randomly divided into 4 groups, which included a control group (OE 0 L/kg bw) as well as low- (OE 12.5 L/kg bw/day), mid- (OE 25 L/kg bw/day), and high-dose (OE 50 L/kg bw/day) groups. Mice were continually administered intraperitoneal injections of OE at different doses for 5 consecutive days. On the 15th and 30th day after treatments, half of the mice were sacrificed separately. The results showed that OE decreased relative ovary weights and prolonged the duration of estrous cycle with concomitant increase in estrous phase. There was a significant decrease in the number of corpora lutea of OE-treated mice, but no significant differences were found in healthy and atretic follicle populations compared to control. Ultrastructure observation regarding granulosa cells of the ovary revealed that OE treatment caused mitochondrial swelling together with endoplasmic reticulum expansion. All these data indicate that OE could exert adverse effects on the development of ovary and also a slight suppressive effect on reproductive functions.

Spawning time variation in Icelandic summer-spawning herring (Clupea harengus)

Different fish stocks of the same species are defined by spatial and temporal differences in spawning, though spawning time can vary within and among stocks. Here we address spawning time variation in Icelandic summer-spawning (ISS) Atlantic herring ( Clupea harengus ). We do so by examining influencing factors that include variation in stock size structure, spawning experience (recruit vs. repeat spawners), spawning stock biomass (SSB), sea temperature, and combinations thereof. Our results, based on temporal variation in ovary weight (OW), relative ovary weight (RG), and maturation stage, across a time series of nearly 50 years and eight length classes of ISS herring, show that spawning occurs over a relatively invariant 30-day period defined by day-of-the-year. Logistic regression analyses and temporal development in OW and RG show that maximum spawning invariably occurs on day-of-the-year 200 ± 15 days, and seasonal variation in mesenteric fat content is physiologically consistent with the timing. We show that the smaller recruit spawners tend to spawn ~17 days later, on average, than the larger repeat spawners. Spawning occurs ~7 days later when SSB is greater than the long-term average, and spawning may be delayed by as much as 10 days during periods of colder than average ocean temperature.

Endocrine disruption and ovarian morphometric responses in rats following exposure to tetradifon

We have investigated whether exposure to tetradifon causes ovary injuries, disrupts folliculogenesis in rat and whether ovary hormones (estrogen and progesterone) to be affected by this endocrine-active agent. Female rats were exposed orally to a dose of 28.9 mg/kg/day for 6 or 12 weeks. After sacrifice, ovary glands were examined for morphometric changes. The serums were used to determine levels of 17β-estradiol and progesterone. Results showed no sign of toxicity. However, tetradifon promoted a significant increase in the percentage of atretic follicles in the 12-weeks treated rats. Number and the diameter of mature follicles (tertiary and preovulatory) were markedly diminished together with a reduction of the relative weight of ovaries. Compared with controls, the treated rats exhibited significant reduction in serum 17β-estradiol and progesterone levels. These results suggest an endocrine disruption by tetradifon which may interfere with ovarian follicles development in rat.

Proteomic Analysis of the Rat Ovary Following Chronic Low-Dose Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (20, 50, or 125 ng/kg once weekly) TCDD for 29 wk. A proteomic analysis of the ovaries by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry showed distinct changes in the levels of several proteins that are relevant markers of TCDD toxicity. Serum estradiol (E2) levels of TCDD-treated animals were markedly lower than control. There were no significant differences in bone mineral density (BMD) of femurs. The body weight of the 125-ng/kg TCDD group was significantly decreased relative to control and there was also a significant reduction in absolute and relative ovarian weights. Expressions of selenium binding protein 2, glutathione S-transferase mu type 3, Lrpap1 protein, NADPH, and peptidylprolyl isomerase D were upregulated, while prohibitin and N-ethylmaleimide-sensitive factor expression levels were downregulated. Data provide further insight into the mechanisms by which TCDD disrupts ovarian function by indicating which differential protein expressions following low-dose TCDD exposure.

Ecology of Phallotorynus pankalos (Cyprinodontiformes: Poeciliidae) in a first-order stream of the upper Paraná Basin

Some aspects of the population ecology of Phallotorynus pankalos in a first-order stream of the Iguatemi River Basin are described based on samples taken from March/2007 to February/2008. A total of 2680 individuals, including 948 males and 1732 females was collected. Adult females are larger than males; theirs mean fecundity was estimated as 6.5 embryos/female. There was a strong correlation between standard length and ovary weight, relative ovary weight, and number of embryos. The size of the first maturation of 50% of female population was estimated as 18.24 mm of standard lenght. High female mortality was observed after the first reproduction and sex ratio presents seasonal variation with higher female proportion in the winter.

Safety evaluation of arachidonic acid rich Mortierella alpina biomass in albino rats—A subchronic study

Safety evaluation of arachidonic acid rich Mortierella alpina biomass was carried out in Wistar rats by acute and subchronic oral toxicity studies. A preliminary acute toxicity study revealed that the biomass was safe at acute doses and that the LD50 exceeded 5000 mg/kg BW, the highest dose used in the study. In subchronic study, rats were fed diet containing 0, 2500, 5000, 10,000, 20,000 and 30,000 mg/kg, M. alpina biomass for a period of 13 weeks. Results indicated that biomass fortification had a positive influence on growth with no overt toxic effects on the survival, food consumption and body weight gain throughout the treatment interlude. The statistically significant changes in relative organ weights, serum biochemical and hematological indices in M. alpina fed groups’ viz., higher relative weights of spleen, liver, brain and ovary in females, reduced hemoglobin concentration in males, elevated WBC counts at highest dose, reduction in serum triglycerides and increased alkaline phosphatase activity were not concomitant with pertinent histopathological changes and hence toxicologically inconsequential. No microscopic or macroscopic lesions attributable to the treatment were manifested in the experimental groups. The results of the present study strongly advocate the safety of M. alpina biomass in rats at levels used in the study.

Collaborative work on evaluation of ovarian toxicity 4) Effects of fertility study of 4-vinylcyclohexene diepoxide in female rats

As part of a collaborative project, 4-vinylcyclohexene diepoxide (VCD), an ovarian toxicant, was intraperitoneally administered to female Sprague-Dawley rats at 0, 5, 20 or 80 mg/kg from 2 weeks prior to mating to Day 7 of gestation. At necropsy, the number of implanted embryos, rate of implantation decreased and the rate of preimplantation loss showed an increasing tendency in the 80 mg/kg group. As for organ weight, decreases in absolute and relative ovary weight were observed in the 80 mg/kg group. Histopathologically, the ovaries showed a decrease in number of small follicles at 80 mg/kg

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.

Influence of 50 Hz Magnetic Field on Sex Hormones and Body, Uterine, and Ovarian Weights of Adult Female Rats

The effects of extremely low-frequency (ELF) magnetic fields on sex hormones of adult female Spague-Dawley rats were investigated. Adult female rats were exposed to a 50 Hz sinusoidal magnetic field at approximately 25 μT (rms) for 18 weeks before they returned to their normal life with unexposed counterparts. Serum level of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), progesterone, and estrogen were measured before, after, and during the exposure. Body and uterine weights were not affected by the field. A significant reduction in absolute and relative ovarian weights in exposed rats was observed when compared with sham-exposed controls (P < 0.05). The reduction in the levels of gonadotropins (FSH and LH) was significant after six weeks of exposure (P < 0.005). FSH levels were affected only on week 6 of exposure while LH remained affected during at 12 and 18 weeks (P < 0.05). Interestingly, no significant effects were found at 6 and 12 weeks after removing the field. The level of progesterone and estrogen was significantly decreased after 12 weeks of exposure (P < 0.05), while no other effects on progesterone level was observed during exposure or after removing the exposure. The level of estrogen was also significantly reduced at 12 weeks after removing the field (P < 0.05). These results suggest possible adverse effect on mammalian fertility and reproduction. The effects of ELF-MF on sex hormones were shown to be partly reversible.

Twenty eight-day dietary toxicity study of Luo Han fruit concentrate in Hsd:SD ® rats

A 28-day dietary study was conducted in Hsd:SD ® rats to evaluate the safety of PureLo ®, a non-caloric powdered concentrate of the Chinese fruit Luo Han Guo, which derives its sweetening properties from triterpene glycosides called mogrosides. Groups of 20 rats (10/sex/group) were fed diets containing 0, 10,000, 30,000, or 100,000 ppm PureLo ® for 28 days (OECD, Redbook 2000). PureLo was well tolerated and produced no significant adverse effects. Reduced body weight and body weight gain in high-dose animals of both sexes were related to sporadic reductions in food consumption; there were no overall differences in feed efficiency. Statistically significant changes in clinical chemistry (decreased bilirubin, increased total protein) and relative organ weights of liver, adrenals, ovaries and/or testes, and epididymides were not correlated with any histopathological findings and were not considered adverse. Although a few clinical and pathological findings suggest possible treatment-related effects, particularly in the high-dose group, these findings were transient, not dose-dependent, non-adverse, inconsistent, occurred only in one sex, and/or not supported by histopathological findings. Under the conditions of this study and based on the toxicological endpoints evaluated, the NOAEL for PureLo ® was 100,000 ppm in the diet, the highest level tested, equivalent to 7.07 and 7.48 g/kg bw/day for male and female rats, respectively.

Reproductive Toxic Effects of Artemisia herba alba Ingestion in Female Spague-dawley Rats

The objectives of this study is to investigate the toxic effects of Artemisia herba Alba (300 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 exposed to Topiramate diet at a concentration of 300 mg/kg/body weight for two periods of time. 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 student's t and Chi-square tests. The effect of Artemisia herba alba exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Artemisia herba alba for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Artemisia herba alba were observed. Exposure to Artemisia herba alba 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 an increase in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Artemisia herba Alba causes adverse effects on the reproductive system and fertility. The results of the current study suggest that ingestion of Artemisia herba alba by adult female rats causes adverse effects on fertility and reproduction.

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.

Effects of cypermethrin and methyl parathion mixtures on hormone levels and immune functions in Wistar rats

To study interaction and dose-related effects of mixed cypermethrin and methyl parathion on endocrine and immune functions, 120 Wistar rats were divided randomly into six groups of ten male and ten female rats, respectively, at the age of 2 months. All groups were force-fed every 2 days for 30 days with cypermethrin 0.0, 8.0, 0.0, 8.0, 1.8, 0.4 mg/kg bw and methyl parathion 0.0, 0.0, 0.23, 0.23, 0.0518, 0.0115 mg/kg bw. Controls received vehicle solvent only. Body weight gain and organ weights were measured. Serum or blood were used to test luteinizing hormone, follicle stimulating hormone, estradiol (E(2)), testosterone, thyroid hormones (T(3), T(4), TSH), IgG, IgA, rate of neutrophil phagocytosis and of lymphocyte transformation. The effects on relative weights of ovaries and adrenals, IgA and rate of lymphocyte transformation were antagonistic interaction; the effect on estradiol was synergistic in female, whereas addictive in male rats; and the other indices indicated addictive interaction. Organ weights were similar in exposed and control animals except for adrenal (heavier in exposed rats, P<0.01). Serum levels of FSH and estradiol were higher in exposed groups than in controls (P<0.01). IgG levels were lower in exposed rats than in controls (P<0.01), and IgA levels were higher in exposed females than in controls (P<0.01). Lymphocyte transformation rates were lower (P<0.01) and neutrophil phagocytosis rates were higher (P<0.01) in exposed rats than in controls. Our results showed that exposure to low-dose mixtures of cypermethrin and methyl parathion may affect hormone levels (especially estradiol) and immune function in rats, and the NOAELs of combined compounds were located at 1/600 LD(50).

Effect of chlorpyrifos-methyl on steroid and thyroid hormones in rat F0- and F1-generations

Chlorpyrifos-methyl (CPM) suppressed androgenic activity in Hershberger assay using castrated rats. Acute oral lowest-observed-adverse-effect-level (LOAEL) and no-observed-adverse-effect-level (NOAEL) was evaluated as 12 and 0.1 mg/kg bw, respectively, based on its major effect of cholinesterase inhibition. Also, repeated oral NOAEL was 0.1 mg/kg bw/day based on adrenal damage in rats. We investigated one-generation reproductive toxicity of CPM focusing on endocrine-disrupting effects by the administration of 1, 10 and 100 mg/kg bw/day CPM to mature SD rats (F0) through pre-mating, mating, gestation and lactation period and to their offspring (F1) until 13 weeks age via gavage. A group treated with corn oil served as vehicle control. In F0 rats, the most affected organs were adrenal glands as increased in weight at all doses of CPM in males and at 10 and 100 mg/kg CPM in females and adrenal vacuolation at CPM 10 and 100 mg/kg. The relative and absolute ovaries and the absolute seminal vesicle weights were decreased but the weights of liver, spleen or kidneys were increased at 100 mg/kg CPM. Parameters representing reproductive performances as mating ratio, gestation length and delivery index were not affected, except for decreased fertility index and numbers of implantation and born pups and a higher male sex ratio of pups at CPM 100 mg/kg. F1 pups exposed to CPM 100 mg/kg in utero and via maternal milk showed lower body weight with changes of absolute or relative weights of brain, ovary, liver, spleen and epididymis and decreased absolute not relative anogenital distance at weanling time. The time of vaginal patency and preputial separation and estrous cycling pattern of F1 rats were not impacted by CPM. After further 10 weeks oral administration until 13 weeks old, adrenal glands, brain, liver, spleen or kidneys tended to be increased, while thyroid gland, testes and ventral prostate of F1 male rats were decreased at CPM 10 or 100 mg/kg. Histopathologically, necrosis or vacuolation of thyroid follicular epithelial cells and adrenal cortical cells were observed at all doses of CPM. Serum levels of estradiol, testosterone, T4 and T3 were significantly lower while TSH and cholesterol were higher in both F1 female and male rats treated with CPM though dose-responsiveness was not clear in F1 females. Decreased sperm were counted in F1 rats at CPM 100 mg/kg. As a whole, LOAEL and NOAEL was evaluated as 10 and 1 mg/kg bw, respectively, based on decreased estradiol and T4 and increased TSH in serum of F1 male rats, and when considering histopathological alteration of adrenal and thyroid glands, LOAEL assumed to be lower than 1 mg/kg bw. This study elucidates that CPM exhibit weak reproductive toxicity in F0 rats exposed at adulthood and negligible effects in F1 offspring exposed in utero and via lactation at weanling, but induce anti-androgenic effect and hypothyroidism after long term exposure from in utero through sexual maturation of F1 rats.

An etheral extract of Kamala ( Mallotus philippinensis ( Moll.Arg) Lam.) seed induce adverse effects on reproductive parameters of female rats

The present study was designed to investigate the adverse effects of indigenous Kamala seed etheral extract on various reproductive parameters of female rats. Animals were treated with various doses (50, 75 and 100 mg/kg body weight, (bw)) of seed extract through gavage for 30 days. Treatment with a higher dose of seed extract (100 mg/kg bw) significantly reduced serum levels of FSH, LH and estradiol. At this dose level, relative weights of ovary and uterus was significantly reduced, whereas lower doses (75 and 50 mg/kg bw) did not show any untoward effect. Qualitative analysis regarding histology of ovary revealed reduction in the developing follicles and an increase in the atretic follicles in treated animals as compared to the untreated. Kamala seed extract-induced follicular atresia was further supported by immunoblot/densitometry analysis that ovarian lysate from treated animal had 2.5 times more bax protein expression compared to control ovaries. The number of ovulated eggs and corpora lutea per animal were reduced significantly. Similarly, higher doses of seed extract reduced number of oestrous cycle, whereas the length of cycle was increased significantly. The oestrous and proestrous phases were reduced, while metestrous and diestrous phases were significantly increased. When the females treated with Kamala seed extract were mated with non-treated males, rate of infertile mating increased in a dose-dependent manner with reduced pregnancy rate and number of implantation sites. Taken together, these data indicate that Kamala reduced serum FSH and LH levels probably by affecting hypothalamic/pituitary axis in treated animals. Thus, reduced levels of FSH and LH and estradiol might have affected the follicular development, quality and number of ovulated eggs, corpora lutea formation, oestrous cycle, establishment and maintenance of pregnancy in treated rats.

A thirteen week dietary toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats

Plant lignan 7-hydroxymatairesinol (7-HMR) is a novel precursor of the mammalian lignan enterolactone. A 13 week toxicity study at dietary levels of 0, 0.25, 1, and 4% (w/w) of potassium acetate complex of 7-HMR (HMRlignan) was conducted in the Wistar rat. These dietary levels resulted in an average daily intake of 160, 640, and 2600 mg HMRlignan/kg body weight/day, respectively. A considerable systemic exposure of HMRlignan was verified by dose-related increases in plasma total (conjugated and unconjugated) concentration of 7-HMR and metabolites enterolactone, 7-hydroxyenterolactone, and matairesinol. Enterolactone appeared to be the major metabolite. Most (>96%) of the circulating 7-HMR and enterolactone was in conjugated form as measured from the low-dose rat plasma samples. HMRlignan exposure did not significantly affect clinical signs, ophthalmoscopy or neurobehavioural observations, and motor activity. Transient reductions in food intake and body weight gain in the mid-and high-dose group were ascribed to decreased palatability of the test feed. Only in males of the high-dose group the body weights remained slightly reduced throughout the study. In the high-dose group the number of thrombocytes (females), and total white blood cell count (males) were increased. Plasma triglycerides were dose-dependently depressed in males of all test groups and in females of the mid- and high-dose group, while plasma total cholesterol, and phospholipids were decreased in high-dose males. These changes, which have also been reported for other (flaxseed) lignans, were not considered to represent adverse effects. The relative weight of the kidneys was increased in males of the high-dose group. The weight of the full and empty caecum showed dose-related increases in males of all treatment groups and in females of the high-dose group. Absolute ovary weights were decreased in all treatment groups while decreases in relative ovary weights were confined to the mid- and high-dose group. In addition, a marginal lengthening of the estrus cycle was noted in high-dose females. Apart from prevention of hyaline droplet nephropathy in all high-dose male rats, there were no treatment-related histopathological alterations. It was concluded that HMRlignan showed weak antiestrogen-like activity which may be mediated through enterolactone metabolite. Based on declined ovary weight, the no observed adverse effect level of HMRlignan was set at 0.25% in feed corresponding to 160 mg/kg body weight/day.

Leached components from dental composites and their effects on fertility of female mice.

This study investigated the effects of leached components from a resin-based dental composite (Z-100) and bisphenol A (BPA) on female mouse fertility. Leached components or BPA (5, 25 and 100 microg kg(-1)) were administered intragastrically daily to the test and distilled water to the control groups for 28 d. Female mice were then mated with sexually mature untreated males and their fertility was assessed. The results revealed a significant reduction in the number of pregnancies--54.5% vs. 100% (control)--in mice treated with the leached components from the dental composite, which also showed an increase of 142% in relative ovary weights. Exposure to 25 and 100 microg kg(-1) BPA resulted in significant increases in the total number of resorptions out of the total number of implantations and significant increases in relative uterine weights. Relative ovarian weights were significantly increased at the highest dose. High performance liquid chromatography analysis showed that tri-(ethylene glycol)-dimethacrylate (TEG-DMA) was the major leached component (total: 5945 microg ml(-1)) from the composite, followed by bisphenol A glycerolate dimethacrylate (BIS-GMA) (total: 2097 microg ml(-1)) and BPA (total: 78 microg ml(-1)). The results suggest that leached components from the dental composite used and commercially purchased BPA have adverse effects on the fertility and reproductive system of female mice.