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PubMed2002

Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet.

Bis(2-ethylhexyl) phthalate (DEHP) was given in the diet to provide levels of 0 (control), 0.01, 0.03, and 0.09% from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. There were no adverse effects of DEHP on either litter size, litter weight or sex ratio at birth. The average body weight of male offspring was significantly decreased in the low-dose group at birth. In behavioural developmental parameters, surface righting at PND 4 was significantly delayed in the low- and middle-dose group in female offspring, and those effects were slightly dose related (P < 0.05). Surface righting at PND 7 was significantly depressed in the high-dose group of male offspring, and those effects were significantly dose related (P < 0.001). That of female offspring was significantly depressed in the low-dose group. The dose level of DEHP in the present study produced few adverse effects in reproductive and neurobehavioural parameters in mice.

Aging↗

PubMed2005

Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice.

Bis(2-ethylhexyl) phthalate (DEHP) was given in the diet to provide levels of 0% (C) or 0.03% (T) from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice. At 9 weeks of age, each female was paired with one male from the same or another treatment groups (cross-mating: C/C, T/C, C/T, T/T), for a period of 5 days. The selected reproductive and neurobehavioural parameters were measured. There were no adverse effects of DEHP on either litter size, litter weight and sex ratio at birth. The average body weight of female offspring was significantly affected in group IV (T/T) at PND 14. In behavioural developmental parameters, swimming direction at PND 4 was significantly accelerated in group III (C/T) in female offspring. In movement activity of exploratory behaviour at 3 weeks of age, number of movement of male offspring was significantly affected in group IV (T/T). The dose level of DEHP in the present cross-mating study produced few adverse effects in reproductive and neurobehavioural parameters in mice.

Animals↗

PubMed1995

Cell proliferation kinetics of normal and tumour tissue in vitro: quiescent reproductive cells and the cycling reproductive fraction.

Current methods for measuring the cell kinetics of human tumours are made and interpreted within the context of a simplistic two compartment model for cell proliferation, consisting of cells that are cycling and those that are not. It is now recognized that the non-cycling compartment of many tumours is heterogeneous, composed of non-reproductive end-stage cells and reproductive cells that are dormant/quiescent. We have developed an in vitro analysis that distinguishes for the first time quiescent reproductive cells from non-reproductive end-stage cells and have integrated this analysis with monolayer clonogenic and suicide assays to simultaneously quantitate the duration of the cell cycle and reproductive cells that are: cycling, quiescent, clonogenic, and non-reproductive end-stage cells. We have defined a new parameter, the Cycling Reproductive Fraction (CRF), which is the cycling cell population referenced specifically to the reproductive cell population. Measurements of CRF from 72 tumour biopsies and from 5 normal foreskins showed that CRF approached 100% in some tumours; however, CRF showed near normal values (< 1%) in others suggesting that cell cycle control may be maintained in some tumours. Because of CRF's improved specificity, we believe that CRF may enhance classification, prognostication, and the optimization and prediction of response to chemotherapy.

Breast Neoplasms↗

PubMed2001

Reproductive and neurobehavioural effects of thiabendazole administered to mice in the diet.

Thiabendazole was given in the diet to provide levels of 0 (control), 0.031, 0.125, and 0.5% from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. The average litter size and weight were significantly reduced in the high-dose group at birth. No adverse effects were observed in the sex ratio at birth. The average body weight of offspring was significantly increased in the low-dose group during the late lactation period, and was significantly reduced in the high-dose group during the lactation period. In the assessment of neurobehavioural parameters, surface righting at postnatal day (PND) 7 was significantly delayed in a dose-related manner in both sexes. Swimming limb movement at PND 14 and olfactory orientation at PND 14 were significantly depressed in the high-dose group in both sexes. In movement activity at 3 weeks of age in the F1 generation, vertical time and number of defaecations were significantly decreased in the high-dose group in female offspring. Several adverse effects on reproductive and neurobehavioural parameters were produced at the highest dose level of thiabendazole used in the present study (equivalent to 700-1800 mg/kg bw/day). Slight, dose-related delays were also seen in surface-righting ability at the two lower dose levels. The lowest close level (equivalent to 50-180 mg/kg bw/day) is approximately 500 times the current acceptable daily intake (ADI) of 0-0.1 mg/kg bw.

Animals↗

PubMedDate not supplied

[The prenatal genotype-dependent modification by glucocorticoids of the morphometric characteristics of the genital system in mice and rats].

Morphometric parameters of the reproductive system have been studied in adult males of four inbred mouse strains and two outbred rat strains after injection of corticosteroids into their mothers at 16 and 18 day of pregnancy. Significant interstrain difference in weight of sex glands was observed. Prenatal injection of corticosteroids decreased high values of features and increased low ones. Hence, the level of corticosteroids during prenatal development plays an important part in regulation of morphometric parameters of the reproductive system of adult rodents. The pattern of action depends on the genotype of an animal and may change under the influence of selection.

Animals↗

PubMed1995

Evaluation of selected parameters of a metabolic profile and levels of cadmium in reproductive organs of rabbits after an experimental administration.

Selected serum parameters of metabolic profile and distribution of cadmium in reproductive organs in rabbits were studied after an acute and subchronic administration. After an i.p. application of cadmium (1.5 mg.kg-1) a significant increase of glucose (5.90 mmol.l-1) and cholesterol (2.22 mmol.l-1) was observed. There were no significant differences in these parameters after the subchronic (5 month) p.o. application. The concentration of AST and ALT significantly decreased after a subchronic p.o. administration (1.0 mg.kg-1) but not after an acute i.p. application. There were no significant differences in the level of total proteins and total lipids. The highest accumulation in reproductive organs (testis, ovary, uterus) was observed after i.p. administration. The level in the testis was 40 times higher than in the control group (0.04 mg.kg-1; 1.93 mg.kg-1), 174 times higher in the ovary (0.03; 5.21) and 65 times higher in the uterus (0.04; 2.59). After a subchronic p.o. application, the concentration was only 2.5 times higher in the testis (0.04; 0.10), 16 times higher in the ovary and 6 times higher in the uterus than in the control group.

Alanine Transaminase↗

PubMed1992

Circulating PgF2alpha and nutritional parameters at parturition in dairy cows with and without retained placenta: Relation to prepartum diet.

Reproductive and biochemical parameters were studied at parturition in multiparous single-carrying Holstein cows. These were compared in animals with (n=14) and without (n=40) a retained placenta and then according to 2 prepartum diets (corn silage/concentrate, n=44; grass silage/concentrate, n=10) in cows with and without retained placentas. Cows with retained placentas had a 4-day shorter gestation period and gave birth to 5 kg-lighter calves than cows without retained placentas. Furthermore, their plasma PGFM -PgF2alpha main metabolite- (3325 vs 5675 pg/ml; P<0.01) and glucose (79.2 vs 95.2 mg/100ml; P<0.05) levels were lower and their protein concentration was higher (85.7 vs 76.5 g/l; P<0.05) than those of cows without retained placentas. Retained placenta incidence in cows fed grass-silage was higher than in cows fed corn-silage (60% vs 18.2%; P<0.05). Cows with retained placentas and fed corn silage had shorter gestation lengths, gave birth to lighter calves, and had less circulating glucose at calving (77.6 vs 96.5 mg/100ml; P<0.05) than cows without retained placentas and fed the same forage. Cows with retained placentas and fed grass silage had less PGFM (2172 vs 4530 pg/ml; P<0.05) than cows without retained placentas and fed the same forage. Calving number, sex ratio and preceeding milk yield were not different between the two groups of cows whatever their prepartum diet. In the dairy cow, retained placenta could be due to a PgF2alpha or an energy deficiency at calving. Roles of the dietary polyunsaturated fatty acids toward the Pg synthesis and of the energy supply before calving in relation to retained placenta are discussed here.

Journal Article↗

PubMed1990

The effect of L-acetylcarnitine on some reproductive functions in the oligoasthenospermic rat.

The effect of L-acetylcarnitine (LAC) on some parameters of male reproductive function was studied on rats made oligoasthenospermic with dibromochloropropane (DBCP). DBCP depresses sperm count and motility. After one injection of the drug, LAC induces a recovery of both sperm count and motility but after two injections it is ineffective. This effect is also shown visually by microscopic examination of seminiferous tubules. Among the enzymatic activities evaluated as biochemical markers of testicular function both lactate dehydrogenase and NADPH-cytochrome P 450-reductase increased significantly (P less than 0.05) after treatment with LAC in normal rats. LAC also stimulates testosterone production. It is suggested that LAC may affect testicular function.

Acetylcarnitine↗

PubMed1995

Male reproductive toxicity of ethinylestradiol associated with 4 weeks daily dosing prior to mating in rats.

Parameters of male reproductive toxicity of ethinylestradiol were assessed by conducting a mating test, sperm assay, organ weight determination and histopathological examination. Male Sprague Dawley rats were orally administered 0.1, 0.3, 3 or 10 mg/kg/day ethinylestradiol for 4 weeks prior to mating. Body weight gain and food consumption were suppressed in all treated groups. Reproductive ability of the 3 and 10 mg/kg/day males disappeared. Slightly low copulation indices were observed in the 0.1 and 0.3 mg/kg/day groups, although fertility indices were not affected. Sperm could hardly be found in the epididymis of 3 and 10 mg/kg/day males. Sperm counts were also decreased in the other treated groups, but sperm motility was not affected. Decreased absolute and/or relative weights of testes, epididymides, prostate and seminal vesicles were observed in all treated groups along with testis, epididymis, seminal vesicle and prostate atrophy, and degenerative changes of spermatocytes, spermatids, Sertoli cells and Leydig cells. These results suggest that sperm quantification and histopathological assessment are more appropriate for assessing male reproductive toxicity of ethinylestradiol than performance of copulation and fertility tests.

Animals↗

PubMed1996

Genetic variation and covariation for ewe reproduction, lamb growth, and lamb scrotal circumference in a fall-lambing sheep flock.

Genetic parameters for female reproduction, lamb growth, and lamb scrotal circumference in a composite population of 50% Dorset, 25% Rambouillet and 25% Finnsheep breeding selected for ability to lamb in fall were estimated by REML using various animal models. Traits considered were spring fertility, litter size, weight at weaning (WWT), 90 d (WT90), and 120 d (WT120), and scrotal circumference at weaning (WSC), 90 d (SC90), and 120 d (SC120). Fertility was defined as 1 or 0 for ewes that lambed or failed to lamb, respectively, in fall and averaged .59 for adults (3 yr and older), .45 for second-lambing ewes, .18 for 19-mo-old ewes, and .11 for 12-mo-old ewes. Heritability estimates for fertility varied among models from .07 to .11. Heritability of fall litter size was .10. For body weights, estimates of additive direct, additive maternal, permanent environmental maternal, and litter effects as proportions of phenotypic variance were .04, .10, .05, and .11, respectively, for WWT, .09, .05, .14, and .01 for WT90, and .18, .0, .13, and .06 for WT120. Heritability estimates for WSC, SC90, and SC120 were .15, .25, and .02, respectively. Estimates of genetic correlations among body weights ranged from .77 to unity. Estimates of genetic correlations of fertility with fall litter size, WT90, and SC90 were .56, -.31, and .29, respectively. Genetic correlations of fall litter size with WT90 and SC90 were .33 and .36, respectively. Estimated genetic correlations revealed no major genetic antagonisms with ability to lamb in fall.

Animals↗

PubMed2002

[Ecologic and social problems of reproductivity in the Irkutsk region].

The study covered quantitative and structural features, changes in functional parameters of female reproductive system, in disorders of pregnancy, childbed and newborns in Irkutsk region. The authors demonstrated role and relationships of some regional factors--natural, ecologic and technogenic, occupational and industrial, social and economic--in formation of reproductivity, disorders during 1980-1990s.

Adolescent↗

PubMed2003

Reproductive and neurobehavioural effects of piperonyl butoxide administered to mice in the diet.

Piperonyl butoxide was given in the diet to mice to provide levels of 0 (control), 0.01, 0.03 and 0.09% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(1) generation, and selected reproductive and neurobehavioural parameters were measured. There were no adverse effects of piperonyl butoxide on either litter size, litter weight or sex ratio at birth. The average body weight of male offspring was significantly increased in the middle-dose group at post-natal days 4 and 7 during lactation. That of female offspring was significantly increased in the middle-dose group at post-natal days 7 and 14 during lactation. In behavioural developmental parameters, surface righting at post-natal day 7 was significantly delayed in the higher-dose groups in male offspring, and those effects were significantly dose related (p < 0.01). Olfactory orientation at post-natal day 14 was significantly depressed in the higher-dose groups in male offspring, and those effects were significantly dose related (p < 0.01). For movement activity of exploratory behaviour at 9 weeks of age of the F(1) generation, the total distance of males was significantly increased in the higher-dose groups, and those effects showed a dose-related manner (p < 0.01). Average distance and speed were significantly increased in the high-dose group, and those effects showed a dose-related manner (p < 0.01 in each). The dose levels of piperonyl butoxide in the present study produced some adverse effects in reproductive and neurobehavioural parameters in mice.

Animals↗

PubMed1991

The effect of piroctone olamine on reproduction of male and female rats.

The purpose of this study was to determine the effect of piroctone olamine, an antidandruff active, on reproductive performance, fertility, parturition, and neonatal viability and growth. Piroctone olamine was administered orally by gavage to three groups of 35 male Sprague-Dawley rats each beginning 64 days prior to mating and continuing until euthanized and to three groups of 35 female Sprague-Dawley rats each beginning 14 days prior to mating and continuing until euthanized. Animals in the treated groups received piroctone olamine in a combination of 1.0% methylcellulose and polyethylene glycol 400 as a single daily dose at levels of 0, 10, 100, and 250 mg/kg/day, at a volume of 2.5 ml/kg. The control group received the vehicle only. Ten randomly selected females/group were mated and underwent a uterine examination on Gestation Day 13; the remaining females were allowed to deliver. Because earlier studies reported hematological effects, blood samples were collected from all parental animals during acclimation and prior to euthanasia for hematological and blood chemistry (Gestation Day 13 females) characterization. The parental animals were necropsied and tissues were grossly examined. Systemic effects induced by the test article were seen at the mid- and high-dose levels but only among the male rats. These effects were reduced body weight and decreased liver weights. Hematological findings representative of anemia occurred at the high-dose level, as did rales in several animals. Offspring growth was inhibited for the high-dose group as evidenced by significantly reduced mean weight values throughout lactation. The remaining parameters assessed, including mating ability and reproductive performance, were not affected by treatment at any dosage level tested. In summary, the no observable effect level of piroctone olamine with respect to systemic toxicity was considered to be 10 mg/kg/day. Neonatal growth was not affected at 100 mg/kg/day or less, and the no observable effect level with respect to reproductive parameters, including fertility, was 250 mg/kg/day.

Animals↗

PubMed2002

Temperature-dependent prolactin secretion and reproductive biology of the newt Triturus carnifex Laur.

The effects of temperature on pituitary prolactin (PRL) gene expression and peripheral levels were studied in both male and female newts obtained from wild conditions during reproductive (Experiment I) and nonreproductive (Experiment II) periods; moreover, changes in parameters related to reproductive function are also described. Male and female newts were taken from a pond in February (Experiment I, reproductive period) and maintained for 1 month in tanks at 4 and 18 degrees C. In male newts kept at 4 degrees C, increase of PRL mRNA in the pituitary and plasma PRL was found compared with that measured in those kept at 18 degrees C. The increase in PRL secretion was parallel to that of plasma androgens and related secondary sexual characteristics (SSC) in males and of plasma estradiol-17beta and vitellogenin in females. On the contrary, in nonreproductive newts (Experiment II), taken from the field in May, no significant changes in plasma PRL, androgens, and SSC were found in those maintained at low temperature (4 degrees C), whereas low temperature significantly increased PRL mRNA expression in the male pituitary and PRL mRNA plus plasma PRL levels in females. These findings suggest that low temperature regulates PRL secretion in this urodele species, showing a sex- and season-related control mechanism; moreover, low temperature failed to influence the reproductive biology of newts taken from the field in May, after naturally occurring reproduction during winter months.

Animals↗

PubMed1983

Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure.

One hundred bred Fischer-344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride-induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty-two C57BL/6 female mice bred to C3H males to produce B6C3F1 offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500-ppm group was terminated on gd 10-14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500-ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo-fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of ethyl chloride.

Air↗

PubMed2000

Reproductive development of male and female tilapia hybrids (Oreochromis niloticus x O. aureus) and changes in mRNA levels of gonadotropin (GtH) Ibeta and IIbeta subunits.

A study was carried out in tilapia in order to see whether the gonadotropin (GtH) beta subunits show distinct patterns of expression at different stages of their reproductive development. Male and female tilapia hybrids (Oreochromis niloticus x O. aureus) were collected at various times of the year, and a number of parameters were measured in order to establish the reproductive state of the fish. Circulating testosterone (T), estradiol (E(2)) and 11 ketotestosterone (11KT) levels were assayed, gonads were removed for calculation of gonadosomatic index (GSI) values and histological studies, and RNA was extracted from the pituitaries for measurement of GtH Ibeta and IIbeta mRNA levels. In maturing fish of both sexes, the circulating steroid levels were positively correlated with each other (r(2) = 0.66-0.91) and in males, also with the GSI values (r(2) = 0.68). A positive correlation was also seen in these fish between GSI values and the prevalence of spermatocytes and spermatids (r(2) = 0.54). In maturing females, the maximal oocyte diameter was positively correlated with circulating E(2) levels (r(2) = 0.63), while GSI values showed no correlation; this presumably relates to the cycling nature of this asynchronous spawner. In regressing fish of both sexes, no clear correlation between these reproductive parameters was seen. In all fish, the GtH Ibeta mRNA levels were highest in fish with steroids ranging 1-10 ng T or E(2)/ml for males or females, respectively, and were lower in fish with steroids at higher or lower levels. In fish with high steroid levels, the IIbeta mRNA levels were also high, and in regressed males the increases were positively correlated. Exposure of cultured pituitary cells to either steroid (T at >10 nM, or E(2) at >1 nM) was followed by a decrease in the steady-state levels of the Ibeta transcript, while those of IIbeta were left unaltered. In situ hybridization studies revealed that in pituitaries of both sexes, the cells producing each of these mRNAs are located in a distinct location. These results suggest that gonadal steroids may exert differential feedback mechanisms at the level of the pituitary to control transcription of each GtH beta subunit in distinct cell types specific for each hormone.

Animals↗

PubMed1998

Differential sensitivity of zonagenesis and vitellogenesis in Atlantic salmon (Salmo salar L) to DDT pesticides.

In Atlantic salmon (Salmo salar L) female sexual maturation entails both zonagenesis and vitellogenesis, both of which are controlled by increasing levels of estradiol-17 beta (E2). Antibodies against salmon zona radiata proteins (eggshell zr-proteins) and vitellogenin were used to monitor induction of oogenesis in juvenile salmon. Molecular weights of zr-monomers were estimated to about 66, 61, and 55 kDa, and to about 180 kDa for vitellogenin. Xenobiotics such as the pesticide DDT impair biological reproduction. The o,p'-DDT (1,1,1-trichloro-2[2-chlorophenyl]-2-[4-chlorophenyl]ethane) isomer seems to be a xenoestrogen. Serum levels of zr-proteins and vitellogenin, and hepatocytic biosynthesis of these components, were determined after in vivo treatment of salmon with DDT (technical, p,p'-(1,1,1-trichloro-2,2-bis[4-chlorophenyl]ethane) or o,p'-DDT) or E2. Exposing fish to frequent doses of o,p'-DDT (25 mg/kg b.w. (body weight) twice a week, six times totally) resulted in induction of all three zr-protein monomers, but not of vitellogenin. In contrast, three weekly injection of 10 mg/kg b.w. of either of the three DDT preparations did not induce typical zr-proteins or vitellogenin in serum. In vivo studies with combined DDT + E2 injections showed that none of the DDT preparations influenced E2-induced biosynthesis of zr-proteins or vitellogenin. E2 induction of these oogenetic processes was not blocked even by a high concentration (125 mg/kg b.w.) of o,p'-DDT. Furthermore, pretreatment of salmon with o,p'-DDT for 2 weeks, followed by one injection of E2, did not antagonize biosynthesis of zr-proteins, but serum concentration of vitellogenin was decreased. The data indicate that in juvenile salmon o,p'-DDT may be xenoestrogenic with regard to zonagenesis, but weakly anti-(xeno)estrogenic with regard to vitellogenesis. These findings suggest new complexities in fish reproductive toxicology of xenoestrogens. Compared to vitellogenesis, zonagenesis is a more sensitive parameter for monitoring reproductive effects of xenoestrogens.

Animals↗

PubMed1999

Progesterone and testosterone concentrations during oestrous cycle and pregnancy in the common vole (Microtus arvalis Pallas).

Serum progesterone and testosterone concentrations were measured during different stages of oestrous and pregnancy in paired and unpaired female common voles (Microtus arvalis). Hormone concentrations were measured by ELISA, and cycle stages were determined by vaginal smears. Paired females usually had serum progesterone concentrations of more than 10 ng/ml in the oestrous cycle. A significant maximum was detected in prooestrous (51.70 +/- 7.84 ng/ml, mean +/- S.D.). Serum progesterone concentrations increased from about 40 ng/ml at the beginning of pregnancy to about 70 ng/ml on days 15 and 16. The last 2 days before parturition (days 19 and 20) were characterised by a decrease of progesterone concentrations to ca. 30 ng/ml. The maximum concentration of testosterone was found in prooestrous (1.58 +/- 0.31 ng/ml). Concentrations during pregnancy varied between 1.5 and 2.1 ng/ml. In two of three cases unpaired females exhibited progesterone values below 10 ng/ml, but with varying vaginal smear patterns. The combination of progesterone concentrations and vaginal smear patterns was found to be regular in only 23.8% of the cases. The most frequent cycle stage found was the oestrous (44.2%). Mean concentrations of progesterone (10.43 +/- 13.81 ng/ml) and testosterone (0.85 +/- 1.11 ng/ml) in unpaired females were significantly lower than in paired females, thereby denoting reproductive inactivity in the former. The study presents basic data for several parameters of the reproductive biology in the common vole and confirms the importance of combining hormone assays and vaginal smear monitoring in reproductive research.

Animals↗