Safety of an oxygen-coordinated niacin-bound chromium(III) complex (NBC): II. Developmental toxicity study in rats

The objective of the present study was to evaluate the teratogenic potential of a novel oxygen-coordinated niacin-bound chromium complex (NBC) in Sprague-Dawley rats. Due to its potential to affect fat synthesis and reduce food intake, processes which are often crucial in normal fetal development, this teratology study was undertaken as part of a multi-generation reproductive investigation. The animals in this study were selected randomly after weaning from each F_2b litter of the F1 generation from the two-generation reproductive toxicity study. To start the teratology study, Sprague-Dawley rat pups (∼30/sex/group) from the F_2b generation were allowed to grow up to 10-12 weeks of age before mating. The rats in treatment group were exposed directly to NBC through feed. The dietary exposure levels were the same as those employed for the two-generation reproductive toxicity study, viz. 4, 15, or 60 ppm. Following mating at maturity, the pregnant rats were observed daily for clinical signs of adverse effects, and body weight and feed consumption were recorded. On the day 20th of the gestation, animals were subjected to a necropsy and caesarean section to examine the uterus, ovaries and fetuses for assessment of different parameters of pregnancy and embryo-fetal defects. In this study, no indications of maternal toxicity, adverse effects on the parameters evaluated for the gravid uteri, external abnormalities in the fetuses, soft tissue abnormalities in the fetuses, or skeletal abnormalities in the fetuses were noted. Based on the results of this developmental toxicity study, NBC was found to benon-teratogenic in Sprague-Dawley rat, at the dietary exposure levels of 4, 15, and 60 ppm, equivalent to the dose levels of 0.50, 2.0, or 8.0 mg/kg/day, respectively.     

Two generation reproduction study of styrene by inhalation in Crl-CD rats

This study was conducted to evaluate the potential adverse effects of styrene on reproductive capability from whole-body inhalation exposure of F0 and F1 parental animals. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F0 and F1 generations, and F1 generation offspring growth and development. Four groups of male and female Crl:CD(SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure for the F0 and F1 females continued throughout mating and gestation through gestation day 20. Inhalation exposure of the F0 and F1 females was suspended from gestation day 21 through lactation day 4. On lactation days 1 through 4, the F0 and F1 females received styrene in virgin olive oil via oral gavage at dose levels of 66, 117, and 300 mg/kg/day (divided into three equal doses, approximately 2 hr apart). These oral dosages were calculated to provide similar maternal blood peak concentrations as provided by the inhalation exposures. Inhalation exposure of the F0 and F1 females was re-initiated on lactation day 5. Styrene exposure did not affect survival or clinical observations. Rats in the 150- and 500-ppm groups in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F0 or F1 generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts and corpora lutea counts for the F1 females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F0 and F1 generations. A previously characterized pattern of degeneration of the olfactory epithelium that lines the dorsal septum and dorsal and medial aspects of the nasal turbinates occurred in the F0 and F1 generation animals from the 500-ppm group. In the 500-ppm group, F2 birthweights were reduced compared to the control and F2 offspring from both the 150- and 500-ppm exposure groups gained weight more slowly than the controls. Based on the results of this study, an exposure level of 50 ppm was considered to be the NOAEL for F0 and F1 parental systemic toxicity; the NOAEL for F0 and F1 reproductive toxicity was 500 ppm or greater.     

Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1‐Generation Mice

Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in the F₁ generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of male offspring decreased significantly in dose‐related manners on postnatal days (PNDs) 0, 4, 7, and 14 (p = 0.0019, 0.0096, 0.033, and 0.038, respectively) during the lactation period. In female offspring, the average body weights decreased in dose‐related manners on PNDs 0, 4, 7, and 14 (p = 0.0027, 0.0104, 0.0193, and 0.0062, respectively). The survival of dams slightly decreased (p = 0.0209) in the high‐dose group during the lactation period. With respect to behavioral developmental parameters, surface righting on PND 7 of male and female offspring was delayed significantly in a dose‐related manner (p < 0.001 in each). Swimming direction on PND 7 of male offspring was delayed significantly in a dose‐related manner (p < 0.01), and for female offspring it was delayed significantly in the high‐dose group (p < 0.05). Swimming head angle on PND 7 of male offspring was delayed significantly in a dose‐related manner (p < 0.05). Spontaneous behavior examination in males indicated that rearing increased in the high‐dose group in the F₁ generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice     

The effects of aluminium ingestion on reproduction and postnatal survival in rats

Aluminium nitrate was tested for its effects on reproduction, gestation, and lactation in Sprague-Dawley rats, at dosages of 0, 180, 360 and 720 mg/kg/day. Mature male rats were treated orally for 60 days prior to mating with mature virgin female rats treated for 14 days prior to mating with treatment continuing throughout mating, gestation, parturition, and weaning of the litters. One-half of the dams in each group were killed on day 13 of gestation and the remaining dams were allowed to deliver and wean their offspring. Postnatal development was monitored. No adverse effects on fertility or general reproductive parameters were evident at doses employed in these studies. However, the survival ratios were higher for the control group. Moreover, a dose-dependent delay in the growth of the living young could be observed in aluminium treated groups. Therefore, it would seem that high amounts of aluminium should not be ingested during the periods of gestation.     

Two-generation reproduction study of di-2-ethylhexyl terephthalate in Crl:CD rats

BACKGROUND: This study was conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) on reproductive capability from exposure of F(0) and F(1) parental animals. METHODS: Four groups of male and female Crl:CD (SD)IGS BR rats (30/gender/group) were exposed to 0, 0.3%, 0.6%, and 1.0% DEHT in the feed for at least 70 consecutive days before mating for the F(0) and F(1) generations. Exposure for the F(0) and F(1) males continued throughout the mating period until euthanasia. Exposure for the F(0) and F(1) females continued throughout mating, gestation, and lactation. The F(1) and F(2) pups were weaned on postnatal day (PND) 21. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F(0) and F(1) generations, and F(1) generation offspring growth and development. RESULTS: DEHT exposure did not affect clinical observations. However, lethality was observed in F(0) and F(1) dams consuming the 1.0% diet during the post-weaning period. No treatment-related mortality occurred in any of the male groups exposed to DEHT or in the female groups exposed to 0.3% or 0.6% DEHT. Male rats consuming the 1.0% diet in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F(0) or F(1) generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size, developmental landmarks, and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts for the F(1) females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F(0) and F(1) generations. CONCLUSIONS: Increases in liver weights were found in the male and female animals exposed to 0.6% or 1.0% DEHT in the diet. Because there were no accompanying histopathologic changes, this effect was not considered adverse. Significant decreases in feed consumption in the female animals from the groups consuming 1.0% DEHT in the diet during lactation accompanied reduced postnatal pup body weights and rate of weight gain. Reductions in pup body weights later in lactation may also have been due to direct consumption of the treated feed by the pups or taste aversion to the same. Reduced relative spleen weight was found in male weanling pups from the 1.0% group in both generations and reduced relative spleen and thymus weights were found in female pups from the 1.0% group in the F(2) generation at necropsy on PND 21. Therefore, for parental and pup systemic toxicity, 0.3% DEHT in the diet (182 mg/kg/day) was considered no-observed-effect level (NOEL). The 1.0% DEHT (614 mg/kg/day) in the diet exposure concentration was considered a NOEL for F(0) and F(1) reproductive toxicity endpoints.     

Reproductive and neurobehavioral effects of maternal exposure to piperonyl butoxide (PBO) in F1‐generation mice

Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide levels of 0 (control), 0.015, 0.03, and 0.06% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in F₁ generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of offspring showed no significant effects of PBO treatment through the lactation period in both sexes except for the low‐dose group of females on PND 21. With respect to behavioral developmental parameters, swimming direction of female offspring on PND 7 was significantly accelerated in the low‐dose group (p = 0.022). Exploratory behavior examination in male offspring indicated that total distance and movement time shortened significantly in dose‐related manners (p = 0.0138 and 0.00231, respectively), average time of rearing lengthened significantly in a dose‐related manner (p = 0.00814), and the frequencies of mice with urination was increased significantly in a dose‐related manner (p < 0.05). For spontaneous behavior examination, the average time of movement in males and average time of rearing in females showed slightly dose‐related effects in the F₁ generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice.     

The reproductive performance of female Formosan sambar deer (Cervus unicolor swinhoei) in semi-domesticated herds

This study documented the reproductive performance of 210 adult female Formosan sambar deer (FSD, Cervus unicolor swinhoei) from four semi-domesticated deer herds in Taiwan. An extensive analysis of 525 reproductive records from 2000 to 2008, including the conditions of estrus, gestation, and parturition was conducted. The mean ± S.E.M. lengths of the estrous cycle, gestation, and fawning interval were 18.2 ± 0.5 d (n = 56), 258.6 ± 0.3 d (n = 160), and 369.9 ± 2.3 d (n = 122), respectively. Hand breeding was performed between June and December (n = 494), with the majority (93.1%) occurring between July and October (P < 0.05). Fawning occurred from February to September (n = 318), and most frequently (83.0%) between April and June (P < 0.05). Pregnancy rate per mating in FSD hinds was 64.4%. There was a 1.3:1 male-to-female ratio at birth (P < 0.05) among 320 fawns, and only two cases of twinning (0.63%). The postnatal mortality rate was 6.6% (21/320), and the mortality rate in fawns before weaning did not exceed 8% on any farm. Fecundity was enhanced by high pregnancy rates and high offspring survival rates. This study provides baseline information on reproductive performance of FSD, which should be valuable to veterinarians and deer industry personnel for management of FSD on farms in subtropical countries.     

An atypical reproductive cycle in a common viviparous Asia Agamid Phrynocephalus vlangalii

Viviparous lizards living in cold climate of high altitude often exhibit atypical reproductive cycles, in which mating and fertilization occur synchronously and annually with parturition occurring at the end of the year. Nevertheless, detailed case studies on atypical reproductive cycles are few. Using anatomical data combined with behavioral observations, we examined the reproductive cycle of a common Asian agamid, Phrynocephalus vlangalii, from a high‐elevation area in Sichuan, China. Male spermiation of P. vlangalii occurred in May, and spermatogenesis began in June and reached a maximum in October. For females, ovulation and fertilization occurred in May, and females developed gestation and pregnancy in 3 months from June to August, without vitellogenesis during this period. Females gave birth synchronously in late August, then vitellogenesis began and lasted until May of the next year. All adult males and females were synchronized in the same reproductive condition each month. The synchronous and annual reproductive cycle of P. vlangalii clearly represents an atypical cycle. The male courtship and mating behaviors were concordant with gonadal cycle and mainly happened in May and June. Despite the short growth period for neonates, they had a high over‐winter survival rate of 84.4%, suggesting that autumn parturition did not generate high costs to this reproductive cycle. We propose that the high over‐winter survival rate of neonates is likely linked with female delayed sexual maturity, female asynchronous vitellogenesis and gestation, large relative clutch mass (RCM), and adult‐offspring burrow sharing behavior during hibernation.     

The effect of interspecific mating on sex ratios in the twospotted spider mite and the Banks grass mite (Acarina: Tetranychidae)

Mixed populations of the twospotted spider mite (TSM),Tetranychus urticae (Koch), and the Banks grass mite (BGM),Oligonychus pratensis (Banks), occur on corn and sorghum plants in late summer in the Great Plains. Interspecific matings between these arrhenotokous species occur readily in the laboratory but yield no female offspring. The effect of interspecific mating on female: male sex ratios was measured by examining the F₁ progeny of females that mated with both heterospecific and conspecific males in no-choice situations. TSM females that mated first with BGM males and then with TSM males produced a smaller percentage of female offspring than TSM females that mated only with TSM males (43.1±5.8 and 78.9±2.8% females, respectively). Similarly, BGM females mated with heterospecific males and then with conspecific males produced fewer female offspring than females mated only with BGM males (55.7±5.2 and 77.5±2.5%, respectively). Lower female: male sex ratios were produced also by BGM females that mated with TSM males after first mating with conspecifics (62.4±3.4%). In mixed populations containing males of both species, females also produced lower female: male sex ratios, but these ratios were not as low as expected based on mating propensities and progeny sex ratios observed in no-choice tests. These data suggest that interspecific mating may substantially reduce female fitness in both mite species by reducing the output of female offspring, but in mixed populations this effect is mitigated by unidentified behavioral mechanisms.     

Implications of maternal nutrient restriction in transgenerational programming of hypertension and endothelial dysfunction across F1-F3 offspring

AimsAn extensive variety of prenatal insults are associated with an increased incidence of metabolic and cardiovascular disorders in adult life. We previously demonstrated that maternal global nutrient restriction during pregnancy leads to increased blood pressure and endothelial dysfunction in the adult offspring. This study aimed to assess whether prenatal exposure to nutritional insult has transgenerational effects in F₂ and F₃ offspring.Main methodsFor this, female Wistar rats were randomly divided into two groups on day 1 of pregnancy: a control group fed standard chow ad libitum and a restricted group fed 50% of the ad libitum intake throughout gestation. At delivery, all animals were fed a standard laboratory chow diet. At 11 weeks of age, one female and one male from each restricted litter were randomly selected and mated with rats from another restricted litters in order to generate the F₂ offspring. The same procedure produced F₃ generation. Similarly, the rats in the control group were bred for each generation.Key FindingsOur findings show that the deleterious effects of maternal nutrient restriction to which the F₀ mothers were exposed may not be limited to the male first generation. In fact, we found that elevated blood pressure, an impaired vasodilatory response to acetylcholine and alterations in NO production were all transferred to the subsequent males from F₂ and F₃ generations.SignificanceOur data show that global nutrient restriction during pregnancy results in a specific phenotype that can be passed transgenerationally to a second and third generation.     

Reproductive and Neurobehavioral Effects of Clothianidin Administered to Mice in the Diet

Clothianidin was given in the diet to provide levels of 0% (control), 0.003%, 0.006%, and 0.012% from 5 weeks of age of the F₀ generation to 11 weeks of age of the F₁ generation in mice. Selected reproductive and neurobehavioral parameters were measured. In exploratory behavior in the F₀ generation, average time of movement, number of rearing, and rearing time of adult males increased significantly in a dose‐related manner. There was no adverse effect of clothianidin on litter size, litter weight, or sex ratio at birth. The average body weight of male and female offspring was increased significantly in a dose‐related manner during the early lactation period. With respect to behavioral developmental parameters, swimming head angle at postnatal day (PND) 7 of male offspring was accelerated significantly in a dose‐related manner. Negative geotaxis at PND 7 of female offspring was accelerated significantly in a dose‐related manner. For movement activity of exploratory behavior in the F₁ generation, number of rearing of female offspring increased significantly in a dose‐related manner. Movement time of adult males increased significantly in a dose‐related manner. The dose levels of clothianidin in the present study produced several adverse effects in neurobehavioral parameters in mice. Nevertheless, it would appear that the levels of the actual dietary intake of clothianidin are unlikely to produce adverse effects in humans.     

Developmental neurotoxicity study of styrene by inhalation in Crl-CD rats

This study was conducted to assess potential adverse functional and/or morphological effects of styrene on the neurological system in the F2 offspring following F0 and F1 generation whole-body inhalation exposures. Four groups of male and female Crl:CD (SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure continued for the F0 and F1 females throughout mating and through gestation day 20. On lactation days 1 through 4, the F0 and F1 females received styrene in virgin olive oil via oral gavage at dose levels of 66, 117, and 300 mg/kg/day (divided into three equal doses, approximately 2 hr apart). Inhalation exposure of the F0 and F1 females was re-initiated on lactation day 5 and continued through weaning of the F1 or F2 pups on postnatal day (PND) 21. Developmental landmarks were assessed in F1 and F2 offspring. The neurological development of randomly selected pups from the F2 generation was assessed by functional observational battery, locomotor activity, acoustic startle response, learning and memory evaluations, brain weights and dimension measurements, and brain morphometric and histologic evaluation. Styrene exposure did not affect survival or the clinical condition of the animals. As expected from previous studies, slight body weight and histopathologic effects on the nasal olfactory epithelium were found in F0 and F1 rats exposed to 500 ppm and, to a lesser extent, 150 ppm. There were no indications of adverse effects on reproductive performance in either the F0 or F1 generation. There were exposure-related reductions in mean body weights of the F1 and F2 offspring from the mid and high-exposure groups and an overall pattern of slightly delayed development evident in the F2 offspring only from the 500-ppm group. This developmental delay included reduced body weight (which continued through day 70) and slightly delayed acquisition of some physical landmarks of development. Styrene exposure of the F0 and F1 animals had no effect on survival, the clinical condition or necropsy findings of the F2 animals. Functional observational battery evaluations conducted for all F1 dams during the gestation and lactation periods and for the F2 offspring were unaffected by styrene exposure. Swimming ability as determined by straight channel escape times measured on PND 24 were increased, and reduced grip strength values were evident for both sexes on PND 45 and 60 in the 500-ppm group compared to controls. There were no other parental exposure-related findings in the F2 pre-weaning and post-weaning functional observational battery assessments, the PND 20 and PND 60 auditory startle habituation parameters, in endpoints of learning and memory performance (escape times and errors) in the Biel water maze task at either testing age, or in activity levels measured on PND 61 in the 500-ppm group. Taken together, the exposure-related developmental and neuromotor changes identified in F2 pups from dams exposed to 500 ppm occurred in endpoints known to be both age- and weight-sensitive parameters, and were observed in the absence of any other remarkable indicators of neurobehavioral toxicity. Based on the results of this study, an exposure level of 50 ppm was considered to be the NOAEL for growth of F2 offspring; an exposure level of 500 ppm was considered to be the NOAEL for F2 developmental neurotoxicity.     

Effects of Maternal Exposure to Imazalil on Behavioral Development in F1‐Generation Mice

Female mice were exposed maternally to imazalil through diet to provide levels of 0 (control), 0.0006, 0.0018, and 0.0054% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in F₁ generation. There was no adverse effect of imazalil on litter size, litter weight, or sex ratio at birth. With respect to behavioral developmental parameters, surface righting on postnatal day 4 of male offspring was delayed significantly in a dose‐related manner (p < 0.05). Regarding exploratory behavior in the F₁ generation, movement time was significantly long (p = 0.0206) in the low‐dose group of males at 8 weeks of age. Spontaneous behavior examination in males indicated that movement time increased but in females decreased in the low‐dose groups in the F₁ generation. The dose levels of imazalil in the present study produced some adverse effects in neurobehavioral parameters in mice.     

Effect of Age,Duration of Exposure,and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat

Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post‐weaning (G/L/PW cohort) to F₁ generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen‐primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F₁ females received the vehicle or ATZ from PND 21–133 or from PND 120–133. Slight reductions in fertility and the percentage of F₁ generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F₁ generation offspring. The onset of puberty was delayed in of the F₁ generation G/L/PW females at doses of 25 and 50 mg/kg/day. F₁ generation females in the PW high‐dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F₁ generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F₁ generation females exposed from gestation through to PND 133 or only for two weeks from PND 120–133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults     

Variation in gestation length among captive reindeer (Rangifer tarandus tarandus)

An estimated 90% of reindeer females are mated in a 10- to 21-d interval and give birth in an equally synchronized manner. Reported gestation length in reindeer is highly variable (range, 203 to 240 d), almost twice the reindeer estrous cycle length. Previously, we identified a significant, negative relationship between gestation length and conception date in a small group of reindeer. In the current study, the negative relationship was investigated in a switchback design, where reindeer were divided into two groups synchronized for early and late mating over a 2-yr trial. Regression analysis of 11 paired observations produced a negative (P < 0.001) association between gestation length and conception date (slope = − 0.31). Dam weight at breeding and prior to parturition, calf birth weight, and calf sex were not significant variables in the regression. Regression analysis of a larger data set from two University of Alaska Fairbanks reindeer herds, where conception date (verified by systemic progesterone) and gestation length were recorded (historical data set), supported previous conclusions (n = 70; slope = −0.37; P < 0.001). Although the calf sex ratio did not differ with gestation length, there was a positive relationship (r² = 0.19; P = 0.014) between male birth weight and gestation length in the larger data set. The negative relationship between conception date and gestation length enhanced calving synchrony, though the limits of gestation plasticity and underlying mechanisms are not clear. The potential role of photoperiod on early embryonic development is discussed.     

Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods.     

Inhalation developmental neurotoxicity study of ethylbenzene in Crl-CD rats

BACKGROUND: This study was conducted to evaluate the potential adverse effects of whole-body inhalation exposure of F0 and F1 parental animals from a 2-generation reproduction study of ethylbenzene on nervous system functional and/or morphologic end points in the F2 offspring from four groups of male and female Crl:CD (SD)IGS BR rats. METHODS: Thirty rats/sex/group for F0 and 25/sex/group for F1 were exposed to 0, 25, 100, and 500 ppm ethylbenzene for six hours daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure for the F0 and F1 females continued throughout mating and gestation through Gestation Day (GD) 20. On lactation days (LD) 1-4, the F0 and F1 females received no inhalation exposure, but instead were administered ethylbenzene in corn oil via oral gavage at dosages estimated to result in similar internal maternal exposure based upon PBPK modeling estimates (0, 26, 90, and 342 mg/kg/day, respectively, divided into three equal doses, approximately two hours apart). Inhalation exposure of the F0 and F1 females was reinitiated on LD 5 and continued through weaning on postnatal day (PND) 21. Survival, body weights, and physical landmarks were assessed in selected F2 offspring. Neurobehavioral development of one F2-generation treatment derived offspring/sex/litter was assessed in a functional observational battery (FOB; PND 4, 11, 22, 45, and 60), motor activity sessions (PND 13, 17, 21, and 61), acoustic startle testing (PND 20 and 60), a Biel water maze learning and memory task (initiated on PND 26 or 62), and in evaluations of whole-brain measurements and brain morphometric and histologic assessments (PND 21 and 72). RESULTS: There were no adverse effects on reproductive performance in either the F0 or F1 parental generations exposed to up to 500 ppm ethylbenzene [Faber et al. Birth Defects Res Part B 77:10-21, 2006]. In the current developmental neurotoxicity component, parental ethylbenzene exposure did not adversely affect offspring survival, clinical condition, body weight parameters, or acquisition of developmental landmarks of the F2-generation treatment derived offspring. There were no alterations in FOB parameters, motor activity counts, acoustic startle endpoints, or Biel water maze performance in offspring attributed to parental ethylbenzene exposure. A few isolated instances of statistically significant differences obtained in the treatment-derived groups occurred sporadically, and were attributed to unusual patterns of development and/or behavior in the concurrent control group. There were no exposure-related differences in any neuropathology parameters in the F2-generation treatment derived offspring. CONCLUSIONS: The no observed adverse effect level (NOAEL) for maternal reproductive toxicity, developmental toxicity, and developmental neurotoxicity in this study was considered to be 500 ppm/342 mg/kg/day ethylbenzene, the highest exposure level tested in the study.     

Effects of gestation temperature on offspring sex and maternal reproduction in a viviparous lizard (Eremias multiocellata) living at high altitude

Temperature-dependent sex determination (TSD) is well studied in many species of reptiles, but little is known on how geographic distribution and altitude affect the sex ratio. In the present study, we focused on a population of a viviparous lizard with TSD (Eremias multiocellata) that lives at high altitudes (≈2900 m) in Tianzhu, Gansu province, China. Gestation temperature had a notable effect on the offspring sex ratio, gestation period, and the mother's body mass. The mothers produced female biased offspring at 25 °C but male biased offspring at 35 °C. All female lizards lost weight during pregnancy, and the least loss of the body mass was observed at 31 °C. The gestation period increased in a non-linear fashion as ambient temperature was reduced. Average litter size was elevated with an increase of gestation temperatures, reached a maximum at 31 °C, and then declined at 35 °C. Compared with a previous study on a Minqin population which lives at a lower altitude (≈1400 m) and warmer climate, the present study obtained a less skewed sex ratio of offspring in the Tianzhu population. Geographic variations also affected offspring morphology between the two populations; females collected from Tianzhu produced larger litters but with a smaller body weight of offspring. These differences may be caused by the adaptive response to the cool climatic and high-altitude environmental conditions.     

Male and female contributions to heterosis in lifetime performance of mice

Summary Six straightbred lines of mice, some of their F₁ crosses and a synthetic line were used to evaluate male and female contributions to heterosis in lifetime performance measured on females. Females from each straightbred line or F₁ crosses were pair-mated randomly at day 42 with either a male of the corresponding genetic group or from a synthetic line, and pairs were maintained for 155 days (lifetime). Each mother was allowed to rear all young born alive until day 18 when the young were discarded. Data were analyzed using a model in which the group mean of lifetime performance was expressed as the sum of (additive direct) genetic and environmental effects for each of the male and female genetic groups used for mating. Comparison of group means for lifetime performance revealed that estimates of F₁ heterosis due to male and female averaged 10 and 9% for number of parturitions during lifetime, 7 and 28% for total number of young born alive, 6 and 31% for total body weight of young born alive, 8 and 33% for total number of young raised to day 18, 9 and 43% for total body weight of young raised to weaning, and 8 and 8% for days from first mating to last parturition. The male's contribution to heterosis in lifetime performance was smaller than female's contribution for productive traits (total number of young born alive and at day 18, and total body weight of young born alive and at day 18), and was nearly equal in reproductive traits (number of parturitions during lifetime and days from first mating to last parturition).Animal Research Centre Contribution No. 1098     

Relatedness Does not Affect Competitive Behavior of Rival Males or Offspring Growth in Multiply Sired Litters of Bank Voles (Myodes glareolus)

Kin selection operates through the fitness of an organism's relatives. In the polyandry context, kin selection may be observable on the one hand in competition between rival males and, on the other hand, in competition between litter mates. Sperm competition theory predicts that males should invest less into mating when competing for fertilizations against a close relative as compared to an unrelated male. We tested this hypothesis with bank voles (Myodes glareolus) by mating each focal male to two females: one of which had previously mated with a full sibling of the focal male and the other one with a male unrelated to the focal male. However, we found no effect of rival male relatedness on mating behavior or proportion of offspring sired by the 2nd male to mate. Possibly, the probability of successive mating of related males with the same female is too low in natural bank vole populations for selection to have fine‐tuned mating behavior in relation to rival male relatedness. Further, polyandry often results in litters sired by multiple males. Litter mates of such litters have a reduced relatedness and are thus expected to be less cooperative during gestation and lactation, which may impair growth. Following double matings with either two full‐sibling males or two unrelated males, we compared offspring growth at birth and during lactation. Against our prediction, there was no difference in growth between litters sired either by two full‐sibling males or by two unrelated males. Either the conflict was not severe enough to be visible with our sample size (N = 16) or it may have been resolved by maternal control of offspring provisioning.