Developmental effects of hyperbilirubinemia.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Both exogenous and endogenous oxytocin (OT) are associated with an attenuated stress response. Increased levels of OT in the early postnatal period have been shown to affect behavior and physiology in rodents, and these effects last into adulthood, suggesting an organizational role for OT during development. We investigated the effects of neonatal exposure to OT on the development of the stress response in male and female prairie voles (Microtus ochrogaster). OT or an OT antagonist (OTA) was administered either on postnatal day 1 (single, D1) or days 1-7 (repeated, D1-7) and then on day 8 the response to social isolation was assessed by quantifying ultrasonic vocalizations (USVs) and measuring plasma corticosterone (CORT). Treatment effects were observed only in females. A single treatment with OTA was associated with a decrease in vocalizations, while repeated treatment produced an increase in vocalizations. A single treatment with either saline or OTA increased basal CORT. The results suggest that endogenous OT may be involved in the development of the stress response in females.
Gestation day 9.5 rat embryos were cultured for 45 h in serum obtained from pregnant rats that had been fed throughout gestation with either a control diet (based on the AIN-93 formulation), a diet supplemented with flaxseed (20% or 40%, w/w), or a diet supplemented with de-fatted flaxseed ("flaxseed meal", 13 or 26%, w/w). The embryos were fixed in neutral formalin at the end of culture. Overall growth and development was assessed, and the presence of abnormalities was noted. A significant inhibition of growth (as determined by crown-rump length) relative to control was observed in embryos cultured in serum from rats fed the 20% flaxseed diet. The incidence of spontaneous heart inversions was increased significantly in the embryos cultured in serum from the 20% flaxseed and 26% flaxseed meal fed rats. The incidence of flexion defects was increased significantly in embryos cultured in serum from 20% flaxseed-fed rats. The lack of an apparent dose response in any of the statistically significant effects suggests that the observed anomalies were chance occurrences unrelated to the treatment group from which serum was obtained. It is therefore concluded that diets high in flaxseed or flaxseed meal do not result in serum factors that are directly embryotoxic to organogenesis-staged rat embryos. This finding is consistent with the findings of a parallel in vivo rat teratology study where no significant embryotoxicity attributable to flaxseed exposure was observed.
Effects of chronic low level (1 mg/kg/day) lead exposure were studied on (1) the density and the binding properties of L, N, and P type voltage-gated Ca2+ influx channels (VGCCs), and (2) the depolarization-induced rise in [Ca2+]i in synaptosomes obtained from the brains of the neonatal (postnatal-day-5) and the adult (postnatal-week-20) rats. Lead exposure started prenatally and continued for either up to postnatal-day-5 or up to postnatal-week-20. The KD and the Bmax values for the binding of nifedipine (antagonist of L type channels), omega-CgTx (a specific antagonist of N type channels) and omega-AgaTx (antagonist of P type channels) to VGCCs in the neonatal samples were less then those in the adult samples. Depolarization increased (1) the density and the antagonist binding-affinity of VGCCs and (2) increased [Ca2+]i in both the neonatal and the adult samples. The depolarization-induced increase in [Ca2+]i in the neonatal samples was lower than that in the adult samples. Chronic low-level lead exposure decreased the densities of L, N, and P type VGCCs and attenuated the depolarization-induced increase in [Ca2+]i in synaptosomes. Chronic low-level lead exposure, however, did not affect the relative ratio of L, N, and P channels, the affinity of VGCCs for antagonists, and the depolarization-induced increase in antagonist binding to VGCCs in synaptosomes. Thus chronic low-level lead exposure during early development and adulthood may decrease the synthesis of VGCCs but not their antagonist binding-affinity in both the neonatal and the adult rats.
Reproductive tract development is influenced by estrogen. The aim of this study was to determine the effects of an environmental estrogenic chemical bisphenol-A (BPA) on prenatal and postnatal development of female mouse reproductive organs. In the prenatal treatment group, BPA or the synthetic estrogen diethylstilbestrol (DES) were given by subcutaneous (s.c.) injections to pregnant mice during gestational days 10-18. Some offspring treated prenatally with 10 and 100 mg/kg bw BPA or 0.67 and 67 microg/kg bw DES were ovariectomized at 30 days and sacrificed at 40 days of age. Vaginal smears were examined in the remaining offspring, then these offspring were mated with normal males. Prenatal exposure to 10 mg/kg BPA reduced the number of mice with corpora lutea compared to sesame oil controls at 30 days, but more than 80% of mice from either prenatally exposed BPA group were fertile at 90 days. Mice exposed prenatally to maternal doses of 67 microg/kg DES were sterile and showed ovary-independent vaginal and uterine epithelial stratification; however, mice exposed prenatally to BPA did not show ovary-independent vaginal and uterine changes. The number of offspring and litter sex ratio from mice exposed prenatally to BPA (10 or 100 mg/kg) or 0.67 microg/kg DES were not different compared to controls. In postnatal treatment group, female mice were given s.c. injections of BPA (15 or 150 microg/pup) or DES (0.3 or 3 microg/pup) for 5 days from the day of birth, then some mice were ovariectomized at 30 days and examined at 40 and 90 days. In the remaining mice, vaginal smears were examined from 61 to 90 days and ovarian histology was evaluated at 90 days. Mice exposed postnatally to 150 microg BPA exhibited ovary-independent vaginal epithelial stratification. Postnatal DES (0.3 and 3 microg) treatment also induced ovary-independent vaginal stratification. Polyovular follicles having more than one oocyte in a follicle were induced by postnatal injections of BPA (150 microg) or DES (0.3 or 3 microg) at 30 days. These findings indicate for the first time that a large dose of BPA can induce ovary-independent vaginal epithelial changes when given postnatally but not prenatally.
Explore the source record for details and available documents.
Recent concerns about the potential of certain chemicals to modulate estrogen-regulated processes have led to questions as to how chemicals should be tested for such effects. Therefore, AIHC has developed a comprehensive, resource-efficient, and flexible tiered strategy for estrogen modulation (EM) testing. Levels of evaluation include Tier 0, in which exposure, along with alerts based on structure-activity, persistence, bioaccumulation, and other data, are assessed to prioritize chemicals for preliminary testing. In Tier I, short term in vitro, ex vivo, and/or in vivo assays are used to obtain a preliminary indication of EM potential. Among these, an in vivo response assay is considered the most reliable at this time. However, none of these tests are intended for risk assessment, but rather to aid in choosing chemicals for further testing and in guiding the extent of that testing. Tier II is aimed at risk assessment and involves whole animal tests that contain EM-sensitive end points (e.g., two-generation reproduction study). Tier III consists of hypothesis-driven research reserved for situations where targeted research can reduce levels of uncertainty. This tiered approach provides a framework for the strategic and effective application of EM test methods to address specific information needs on a case by case basis.
The effects of daily three 1-h exposures to 7000 ppm 1,1,1-trichloroethane (TCE) on physical and behavioral development were examined in Sprague-Dawley rats exposed during the last week of gestation. A sham group was exposed to filtered air. Offspring of both groups were fostered to untreated dams. No significant group differences were detected in total maternal weight gain or food and water consumption, but differences were observed in initial litter characteristics, including a longer gestation period in the TCE group, a smaller number of litters delivered in the TCE group, and fewer live pups per litter in the TCE group. At birth, the total litter weight was less in the TCE group, but there was no significant difference in average pup weight. Pups prenatally exposed to TCE did not differ from shams in day of eye opening, pinnae detachment, or incisor eruption. The TCE group weighed less the first 2 weeks of life, was impaired in its ability to perform the inverted screen, negative geotaxis, and vertical screen tests, and had less forelimb grip strength. Locomotor activity was reduced in the TCE group, and the ratio of brain to body weight was reduced in TCE-exposed offspring. These data provide evidence for neurobehavioral teratogenicity of intermittent prenatal exposure to high concentrations of TCE in rats.
Many estrogenic chemicals found in the environment (xenoestrogens) show a lower affinity for plasma estrogen binding proteins relative to the natural estrogens such as estradiol. These binding proteins, which include alphafetoprotein in rats and mice, sex hormone binding globulin in humans, and albumin in all species, regulate estrogen uptake into tissues. Therefore, the in vivo estrogenic potency relative to estradiol of xenoestrogens that show lower binding to these serum proteins will thus be underestimated in assays that compare the potency of xenoestrogens to estradiol and do not take serum binding into account. We have examined the effects of the binding components in serum on the uptake of a number of xenoestrogens into intact MCF-7 human breast cancer cells. Since most estrogenic chemicals are not available in radiolabeled form, their uptake is determined by competition with [3H]estradiol for binding to estrogen receptors (ER) in an 18-h assay. Serum modified access (SMA) of cell uptake of xenoestrogens is calculated as the RBA in serum-free-medium divided by the RBA in serum, and the bioactive free fraction of xenoestrogen in serum is then also calculated. We predicted the concentration of two xenoestrogens, bisphenol A and octylphenol, required to alter development of the prostate in male mouse fetuses. Whereas octylphenol was predicted to be a more potent estrogen than bisphenol A when tested in serum-free medium, our assay predicted that bisphenol A would be over 500-times more potent than octylphenol in fetal mice. The finding that administration of bisphenol A at a physiologically relevant dose predicted from our in vitro assay to pregnant mice from gestation day 11 to 17 increased adult prostate weight in male offspring relative to controls (similar to the effect of estradiol), while the same doses of octylphenol did not alter prostate development, provided support for our hypothesis.
The contributions to the recognition of emotional signals of (a) experience and learning versus (b) internal predispositions are difficult to investigate because children are virtually always exposed to complex emotional experiences from birth. The recognition of emotion among physically abused and physically neglected preschoolers was assessed in order to examine the effects of atypical experience on emotional development. In Experiment 1, children matched a facial expression to an emotional situation. Neglected children had more difficulty discriminating emotional expressions than did control or physically abused children. Physically abused children displayed a response bias for angry facial expressions. In Experiment 2, children rated the similarity of facial expressions. Control children viewed discrete emotions as dissimilar, neglected children saw fewer distinctions between emotions, and physically abused children showed the most variance across emotions. These results suggest that to the extent that children's experience with the world varies, so too will their interpretation and understanding of emotional signals.
Explore the source record for details and available documents.
Craniofacial morphology and occlusal pattern are evaluated in 71 subjects having impaired breathing as diagnosed by an otolaryngologist, and in an equal number of controls. The impaired group demonstrate characteristic combinations of craniofacial deformities and malocclusions, with the younger individuals demonstrating a lesser expression of malocclusion progression and morphologic deformities. This suggests that early recognition of such facial patterns may be utilized to identify those breathing compromised individuals who have a likely tendency to develop certain types of malocclusion.
Explore the source record for details and available documents.
Matings of female DDK mice with males of the BALB/c strain are sterile, whereas reciprocal crosses are normally fertile. We used nuclear transplantation between the hybrid eggs of these two strains to investigate the basis of this effect. We demonstrate that the observed sterility results from early embryonic mortality, that the mortality is due to a modification of the egg cytoplasm, and that the modification is mediated by the male pronucleus. Once established, this modification may affect female pronuclei of unrelated genotype such as C57BL/6. These results support the notion that a product derived from the male genome acts at the pronuclear stage and can affect later stages of embryonic development.
Rat c-erbA beta 1 mRNA rises in cerebrum during the first 10 days of life, coincident with an increase in tissue triiodothyronine (T3) levels and T3-dependent brain development. These data suggest that the beta 1 receptor may mediate the T3 effect. However, in cerebellum c-erbA beta 1 mRNA levels were very low. Since cerebellar development, including dendritic arborization of Purkinje cells, is a T3-sensitive process, we assessed the levels of the beta 1 receptor protein in cerebellum during development. Antisera to unique peptide regions of beta 1 were raised. Their specificity was demonstrated by specific immunoprecipitation of the in vitro translated product, 85% immunoprecipitation of the T3 binding activity in hepatic nuclear extracts, and Western blot analysis of tissue extracts. Immunohistochemical studies using anti-beta 1 antiserum stained liver nuclei but not testis nuclei, which contain no T3 binding activity or beta 1 mRNA. In cerebellar Purkinje cells, an immunofluorescent signal, localized to the nucleus and more intense than that seen in the liver, was observed. A positive but weaker signal was also present in the granule cells. Thus, we may infer that the cerebellum contains significant concentrations of beta 1 receptor protein despite the low beta 1 mRNA content. Both the intensity of staining in Purkinje cell nuclei and immunoprecipitable beta 1 receptor binding capacity rose in the neonatal period. Antiserum to the non-T3 binding alpha 2 variant protein was also prepared and a distinctive pattern of fluorescence was observed. Strong fluorescence was seen in the nuclei of granule cells, but none was seen in Purkinje cells. The alpha 2 fluorescence in testis was high, consistent with the high levels of alpha 2 mRNA in this tissue. The fluorescent signal appeared to originate primarily in dividing spermatogonia. Our findings support the concept that the beta 1 receptor plays a central role in T3-induced brain development and strongly suggest that the Purkinje cell is a direct target for T3.
Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced fetal cardiovascular anomalies at doses as low as 1 mg/kg/d (Smith et al., 1988). A slight but possibly biologically significant increase over the water control group in adverse pregnancy outcomes (resorptions, reduced fetal weight, and anomalies) was observed in the Tricap control group. This led us to reexamine the development effects of TCAN in a second vehicle, corn oil (CO). Five groups of approximately 20 pregnant female rats received TCAN in CO at 15, 35, 55, and 75 mg/kg/d, and in Tricap at 15 mg/kg/d (10 ml/kg dosing volume). Corn oil, Tricap, and water served as vehicle controls. Animals were treated by oral intubation on gestation d 6-18 (vaginal plug = d 0). Five out of 20 dams (75 mg/kg) died during treatment. Adjusted maternal weight gain was lower in females receiving 35 mg/kg TCAN or greater. The mean percent of nonlive implants per litter was elevated at 55 and 75 mg/kg TCAN (CO). The TCAN dose-response curve for fetal (but not maternal) effects was shifted to the right when CO was compared to Tricap. Fetal weight was reduced at 15 mg/kg TCAN (Tricap) and at > or = 55 mg/kg TCAN (CO). When TCAN was administered in CO, the mean frequency of soft-tissue malformations decreased with significantly fewer septal and great vessel cardiovascular defects observed. We hypothesize that the volatile haloacetonitrile, TCAN, may interact with the Tricap vehicle in such a way that effects on the developing cardiovascular system are potentiated. The lowest observed adverse effect level for TCAN (CO) was determined to be 35 kg/kg.
A distillate of light alkylate naphtha (CAS number 64741-66-8; LAN distillate) was administered via inhalation, 6 h/d, 7 d/wk to 4 groups of Sprague-Dawley rats (10/sex/dose) at target concentrations of 0 (filtered air control), 5, 12.5, or 25 g/m3 with the highest dose exceeding 60% of the lower explosive limit of LAND. Exposure began 2 wk prior to mating and continued throughout gestation until postnatal d 4 for females or for 8 consecutive weeks for males. No apparent clinical signs indicative of systemic toxicity were observed in the F0 and F1 animals of either sex. Inhalation exposure to LAND up to and including the 25 g/m3 dose level had no effect on parental food consumption, body weights, absolute and relative organ weights, and reproductive indices. All groups had comparable delivery data and a fertility index > or 80%. Pups in all groups showed comparable birth weights, weight gain, a viability index (postnatal d 4) for all groups of > or = 97%, and no histopathological changes. In the dams, there were no significant differences in the mean numbers of corpora lutea, implantation sites, and resorptions recorded at necropsy. In the males, the only remarkable findings at necropsy were a small right epididymis and testis seen in one mid-dose male and an abscess on the right epididymis of a high-dose male. In both cases, the dams that had been bred to these males produced normal litters. There were no test material-related microscopic changes observed in the testes and epididymis of the F0 male rats or ovaries of the F0 female rats exposed to LAND. Under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for LAND via inhalation in rats is established at greater than 24.7 g/m3 (analytical concentration).
Development of hard clam (Mercenaria mercenaria) larvae was examined as a potential biomarker of exposure to polychlorinated biphenyls (PCBs). Clams from clean sites in Massachusetts Bay were thermally induced to spawn in the laboratory using seawater, and the gametes were collected and pooled by sex prior to fertilization. The larvae were cultured in seawater amended with Aroclor 1254, at concentration ranges bracketing environmentally relevant levels. A dose-response relationship was observed for larval development in the presence of Aroclor 1254; at higher doses, fewer larvae developed to the normal straight-hinge, or D-shaped stage, relative to the controls, while the number of abnormally shaped larvae increased.