Serum Of Dams Research Articles

Stage‐specific changes in the levels of granulocyte‐macrophage colony‐stimulating factor and its receptor in the biological fluid and organ of mouse fetuses

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that has neurotrophic and neuroprotective functions. However, its function in the mid- to late-gestational fetus remains unclear. We used enzyme-linked immunosorbent assay to analyze GM-CSF levels in cerebrospinal fluid (CSF), serum, and amniotic fluid of mouse fetuses. We also examined GM-CSF and receptor α (GM-CSFRα) levels in the fetal brain, liver, and placenta. GM-CSF peaked between embryonic day (E) 14 and E15 in the CSF. GM-CSF level was higher in the fetal serum than in the dam serum on E13 and decreased thereafter. GM-CSF and GM-CSFRα levels peaked between E13 and E15 in the brain. These results suggest that GM-CSF plays stage- and organ-specific roles in fetal development.

Vaccine-induced antibodies linked to bovine neonatal pancytopenia (BNP) recognize cattle major histocompatibility complex class I (MHC I).

A mysterious disease affecting calves, named bovine neonatal pancytopenia (BNP), emerged in 2007 in several European countries. Epidemiological studies revealed a connection between BNP and vaccination with an inactivated vaccine against bovine virus diarrhea (BVD). Alloantibodies reacting with blood leukocytes of calves were detected in serum and colostrum of dams, which have given birth to calves affected by BNP. To understand the linkage between vaccination and the development of alloantibodies, we determined the antigens reacting with these alloantibodies. Immunoprecipitation of surface proteins from bovine leukocytes and kidney cells using sera from dams with a confirmed case of BNP in their gestation history reacted with two dominant protein species of 44 and 12 kDa. These proteins were not detected by sera from dams, free of BVDV and not vaccinated against BVD, and from sera of animals vaccinated with a different inactivated BVD vaccine. The 44 kDa protein was identified by mass spectrometry analysis as MHC I, the other as β-2-microglobulin. The presence of major histocompatibility complex class I (MHC I) in the vaccine was confirmed by Western blot using a MHC I specific monoclonal antibody. A model of BNP pathogenesis is proposed.

Lactational transfer of bisphenol A in Sprague–Dawley rats

Bisphenol A (BPA), an important industrial chemical to which humans are exposed on a daily basis, has long been associated with endocrine disruption in experimental animal models. Such exposures are of concern, particularly during fetal and early neonatal periods, because of greater vulnerability of developing organs to aberrant endocrine signaling. Although rarely reported, information about internal exposures to the receptor-active aglycone form of BPA during the perinatal period is essential to accurate assessment of potential risks. Lactating Sprague–Dawley dams were treated by daily gavage with 100 μg/kg bw d6-BPA starting at birth. Conjugated and aglycone forms of BPA were then measured by using LC/MS/MS in milk from lactating dams on PND 7 and in serum from dams and their pups on PND 10. All samples were collected 1 h after dosing, a time selected to produce nearly maximal levels. While aglycone BPA was detected in all dam serum and milk samples, none was detected in pup serum (<0.2 nM). Doses delivered to pups lactationally, estimated from milk concentrations and body weights, were 300-fold lower than the dose administered to the dams. Similarly, serum concentrations of total BPA in pups were 300-fold lower than those in their dams. Furthermore, plasma concentrations of total BPA in PND 10 rat pups were 500-fold lower than peak levels achieved following direct oral delivery of the same dose to the same age pups. These findings of significant dose attenuation for the active aglycone form of BPA, relative to that of the dam, suggest high potency for toxicological effects derived exclusively from lactational transfer. Alternatively, studies that include lactational exposure and report minimal effects from BPA should consider the possibility that inadequate internal exposures were achieved during the critical postnatal period.

Gestational and lactational exposure to potassium perfluorooctanesulfonate (K+PFOS) in rats: Toxicokinetics, thyroid hormone status, and related gene expression

Perfluorooctanesulfonate (PFOS), a persistent and accumulative compound, is widely distributed in humans and wildlife. Human exposure can occur early in development, as evidenced by the detection of PFOS in umbilical cord blood and breast milk. As part of a developmental neurotoxicology study for which developmental endpoints, including those related to the developing nervous system, have been reported separately, groups of 25 pregnant Sprague Dawley rats were given daily oral doses of either vehicle control or potassium PFOS (K+PFOS) at 0.1, 0.3, and 1.0mg/kg-d from gestation day (GD) 0 (day positive for mating) through postnatal day (PND) 20. An additional 10 pregnant females per treatment group were treated through GD 19 and sacrificed on GD 20 in order to obtain maternal and fetal serum and tissue samples at the end of gestation. The present paper reports the results of samples of serum, liver, brain, and thyroid glands taken at various times to evaluate: (1) serum, liver, and brain PFOS concentrations by LC–MS/MS to establish the relationship between PFOS concentrations and study outcomes; (2) serum thyrotropin (TSH) concentrations by RIA; (3) thyroid follicular cell proliferation index by Ki-67 immunohistochemical staining; (4) thyroid follicle epithelial cell height and colloidal area by histomorphometric analysis; (5) selected liver mRNA transcripts by quantitative RT-PCR. PFOS concentrations in dam and pup serum, liver, and brain increased across treatment groups in approximate proportion to the proportional increases in maternal K+PFOS dose, and sex differences in PFOS concentrations were not apparent in pups on PND 21. In pups from K+PFOS maternal dose groups on PND 72, serum PFOS had decreased to about 3 and 11% of PND 21 concentrations in males and females, respectively, and liver PFOS had decreased to about 17% of PND 21 concentrations in both sexes. Liver PFOS concentrations were approximately 0.6–0.8 times serum PFOS in GD 20 fetuses, and increased to about 2–4 times serum concentrations on PND 4 and 21. GD 20 fetal and PND 4 pup brain PFOS concentrations were approximately 33% of the corresponding serum concentrations, dropping to approximately 10% by PND 21, in contrast to dam brain PFOS concentrations, which were approximately 4–9% of serum PFOS concentrations. Compared to controls, Cyp2b2 mRNA was increased (2.8-fold) in the 1.0mg/kg-d treatment-group dams on GD 20. In male pups on PND 21, Cyp4A1, ACoA, and Cyp2b2 were increased 2.1-, 1.5-, and 1.8-fold, respectively, and Cyp7A1 was decreased 3.5-fold. Serum TSH and thyroid follicular morphology were not altered by K+PFOS treatment. The mean number of proliferating thyroid follicular cells was increased 2.1-fold over control in GD 20 female fetuses from 1.0mg/kg-d-treated dams, yet the highest individual count was similar to that of controls (116 versus 113 in controls).

Analysis of PFOA in dosed CD1 mice: Part 1. Methods development for the analysis of tissues and fluids from pregnant and lactating mice and their pups

The number of studies involving the analysis of perfluorooctanoic acid (PFOA) has increased recently because PFOA is routinely detected in human blood samples from around the world. Recent studies with mice have shown that dosing pregnant dams with PFOA during gestation gives rise to a dose-dependent mortality in the litters, a reduction in neonatal body weight for the surviving pups, and subsequent deficits in mammary gland development when compared to control animals. The actual body burdens of PFOA in dams and pups associated with these endpoints have not been determined, in part due to a lack of robust analytical methods for these matrices. The goal of the current study was to develop reliable methods with acceptable performance characteristics for the analysis of PFOA in several matrices relevant to pregnant mouse studies. Dam and pup serum, amniotic fluid, urine, milk, mammary tissue, and whole mouse pups were isolated for method development and analysis. The resulting method provided excellent accuracy (92.1–111%) and reproducibility (relative standard deviation 4.3–21%) making them very useful for future studies. These methods were then applied to dosed animal fluids and tissues in order to conduct a thorough evaluation of the pharmacokinetics in utero. Resulting tissue specific measurements of PFOA in serum, amniotic fluid, urine, milk, mammary tissue, and whole pup homogenate will be used to more completely describe the dose–response relationships for the most sensitive health outcomes and inform pharmacokinetic models that are being developed and evaluated.

Dose- and Route-Dependent Teratogenicity, Toxicity, and Pharmacokinetic Profiles of the Hedgehog Signaling Antagonist Cyclopamine in the Mouse

The Hedgehog (Hh) signaling pathway is an essential regulator of embryonic development and appears to play important roles in postnatal repair and cancer progression and metastasis. The teratogenic Veratrum alkaloid cyclopamine is a potent Hh antagonist and is used experimentally both in vitro and in vivo to investigate the role of Hh signaling in diverse biological processes. Here, we set out to establish an administration regimen for cyclopamine-induced teratogenicity in the mouse. The dysmorphogenic concentration of cyclopamine was determined in vitro via mouse whole-embryo culture assays to be 2.0 microM. We administered cyclopamine to female C57BL/6J mice at varied doses by oral gavage, ip injection, or osmotic pump infusion and assessed toxicity and pharmacokinetic (PK) models. Bolus administration was limited by toxicity and rapid clearance. In vivo cyclopamine infusion at 160 mg/kg/day yielded a dam serum steady-state concentration of approximately 2 microM with a corresponding amniotic fluid concentration of approximately 1.5 microM. Gross facial defects were induced in 30% of cyclopamine-exposed litters, with affected embryos exhibiting cleft lip and palate. This is the first report describing the PKs and teratogenic potential of cyclopamine in the mouse and demonstrates that transient Hh signaling inhibition induces facial clefting anomalies in the mouse that mimic common human birth defects.

Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated oxidative stress

Conjugated linoleic acid (CLA) exhibits anticancer and anti-inflammatory properties. Its ability to increase total GSH (GSH+GSSG) amount and gamma-glutamylcysteine ligase (γGCL) protein expression was recently associated with the inhibition of typical pathological signs in MRL/MpJ-Fas lpr mice (MRL/ lpr). In the present study the ability of CLA to modulate oxidative stress and phase 2 enzyme activity in the same animal model was investigated. Disease severity was associated with age-dependent production of anti-double-stranded DNA antibodies (anti-dsDNA IgGs) and with enhanced extent of oxidative stress markers: reduced total GSH, increased protein 3-nitrotyrosines (3-NT), and protein-bound carbonyl (PC) amounts. To examine the effect of CLA on antioxidant status, CLA or olive oil (as control) was administered to pregnant MRL/ lpr mice. Significantly higher total GSH and Trolox equivalent antioxidant capacity (TEAC) levels were measured in serum of CLA-treated dams (and their pups), as compared with controls. Finally, the antioxidant and chemopreventive properties of CLA were investigated in old MRL/ lpr mice. Sera of CLA-treated mice contained higher concentrations of total GSH which were negatively correlated with the levels of oxidative stress markers. Moreover, increased GSH, γGCL, glutathione S-transferase (GSTs), and NAD(P)H:quinone oxidoreductase (NQO1) activities were measured in liver and spleen of CLA-treated animals. In conclusion our data indicate that the activation of detoxifying enzymes may be one of the mechanisms whereby dietary CLA down-regulates oxidative stress in MRL/ lpr mice.

Detection of 2,4-dichlorophenoxyacetic acid in rat milk of dams exposed during lactation and milk analysis of their major components

2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely used to control the growth of broadleaf and woody plant. Human and animal exposure to 2,4-D through agriculture use, food products, or use in lawn and garden care has been well documented, but little information is available on the transfer from serum to milk in exposed dams. In this study, we measured the content of 2,4-D in rat milk from mother exposed to 15, 25, 50 or 70 mg 2,4-D/kg bw through the diet (4 treated groups, 8 dam each; 1 control group with 8 dams) over a period of 16 days starting on the post-natal day 1 (PND 1). The effect of 2,4-D on milk components was also evaluated. All doses tested caused a decrease in the body weight gain of the pups (4 groups, 64 pups each). It also produce a 30% in the content of total lipids and a changed the content of minor proteins in milk of the treated groups. 2,4-D produces an important decrease in some fatty acids content, being the polyunsaturated fatty acids the most affected. Further analysis showed that 2,4-D concentrations chromatographically detected both serum of dams and pups and milk were dose-dependent.

Experimental encephalomyocarditis virus infection in pregnant mice

The present study was carried out to clarify the mode of encephalomyocarditis (EMC) virus infection in pregnant mice. Pregnant BALB/c mice were intraperitoneally inoculated with the D variant of EMC virus (EMC-D) (5 × 10 2 PFU/mouse) on 11 days of gestation and killed at 1, 3, and 5 days post-inoculation (DPI). The virus titer (dam's serum, placenta, and fetus), histopathology (fetus, placenta, and uterus), distribution of viral RNA (fetus, placenta and uterus), and ultrastructure (fetal heart and placenta) were examined. No deaths occurred to fetuses at 1 DPI but almost all fetuses died at 5 DPI. The virus titers of dam's serum and placenta were elevated at 1 DPI, peaked at 3 DPI, and the former was not detected at 5 DPI. The virus titer of fetus was first elevated at 3 DPI and the level was lower than those of others. Histopathological changes and signals of viral RNAs detected by in situ hybridization (ISH) were observed in the spongiotrophoblast layer of placenta and in the fetal myocardium and liver at 3 DPI. The uterus was free from lesions and signals of viral RNA. Ultrastructural changes developed in trophoblast cells and giant cells in the spongiotrophoblast layer at and after 1 DPI and in fetal myocardial cells at 3 DPI. In the cytoplasm of trophoblast cells and giant cells, aggregations of virus-like particles 20–30 nm in diameter were observed in crystalline array. These results suggest that trophoblast cells and giant cells in the spongiotrophoblast layer are the main target of EMC virus in the placenta and that placental damage as well as the direct effect of virus to fetuses may be a cause of fetal death.

Maternal exposure to low doses of bisphenol a has no effects on development of female reproductive tract and uterine carcinogenesis in Donryu rats.

Effects of maternal exposure to low doses of bisphenol A (BPA), including those comparable with human exposure levels, on growth and development of the female reproductive system and uterine carcinogenesis in Donryu rats were investigated. Dams were administered BPA (0, 0.006 and 6 mg/kg/day) daily by gavage from gestation day 2 up to the day before weaning (postnatal day 21 at offspring). The serum levels of BPA were significantly elevated in the dams receiving 6 mg/kg/day, however, BPA levels in the milk of dams, and those in the serum and liver of offspring were similar between control and treated groups. The treatment did not exert any influences on uterine development including weight, gland genesis and estrogen receptor alpha expression, vaginal opening and gonadotropin secretion in the female offspring up to puberty. After maturation, no effects were evident with regard to estrous cyclicity in female offspring treated with BPA. In addition, the treatment had no effects on age-related morphological changes of the reproductive and endocrine organs and uterine carcinogenesis until 15 months of age. The results demonstrate that maternal exposure to BPA at levels comparable to human exposure did not have any effects on the female reproductive system of offspring in rats. In addition, BPA was also found in the serum, milk and liver of control dams and pups, and low levels of BPA were detected in drinking water and pellet diet. The present study showed that the experimental animals were also exposed to environmental BPA in the animal room.

Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice.

Epidemiological studies have shown a potential association between maternal periodontitis and pregnancy complications. We used a pregnant murine model to study the effect of infection with the periodontal pathogen Porphyromonas gingivalis on pregnancy outcomes. Female BALB/c mice were inoculated with heat-killed P. gingivalis (10(9) CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with live P. gingivalis (10(7) CFU) (n = 20) or broth (control; n = 8) and sacrificed at GD 16.5. Fetal growth restriction (FGR, <0.46 g) was defined as fetuses with weights 2 standard deviations (SD) smaller than controls (0.56 +/- 0.05 g [mean +/- SD]). Among the 20 challenged mice, 8 had both normal-weight (0.51 +/- 0.11 g) and FGR (0.34 +/- 0.1 g) fetuses within the same litter. All other challenged dams had normal-weight fetuses (0.57 +/- 0.04 g). Maternal liver, uterus, and spleen samples were examined for P. gingivalis DNA using a PCR technique. Of the eight challenged mice with FGR fetuses, three had PCR signals for P. gingivalis in liver and uterus, but not in the spleen. Liver, uterus, and spleen were negative for P. gingivalis DNA among all other challenged and control mice. In serum of dams with FGR fetuses, tumor necrosis factor alpha levels were elevated significantly, while interleukin-10 levels were significantly reduced compared to levels in dams with normal fetuses. P. gingivalis-specific serum immunoglobulin G levels were significantly elevated in dams with FGR fetuses compared to dams without any FGR fetuses. These data demonstrate that P. gingivalis-induced murine FGR is associated with systemic dissemination of the organism and activated maternal immune and inflammatory responses.

Flaxseed increased α-linolenic and eicosapentaenoic acid and decreased arachidonic acid in serum and tissues of rat dams and offspring

The effects of dietary flaxseed (FS), and defatted flaxseed meal (FLM) on serum and tissue fatty acid profiles were investigated. Pregnant Sprague–Dawley rats were fed AIN-93 based diets balanced in calories, fat, nitrogen, and fiber. Diets contained 0, 20%, 40% FS or 13% or 26% FLM by weight. The control, FS and FLM diets differed in linoleic acid to α-linolenic acid (ALA) fatty acid ratio. These diets were fed continuously during gestation, suckling period and 8 weeks post-weaning (F 1). FS fatty acids were bioavailable and metabolized by pregnant and F 1 rats. ALA and eicosapentaenoic acid increased; linoleic and arachidonic acid decreased; and docosahexaeonic acid was unchanged in serum, ‘gastric milk’ and liver of FS and FLM-fed pregnant and F 1 rats. FS more than FLM, changed fatty acids profiles, but FLM and 40% FS significantly reduced serum cholesterol. Dietary 40% FS may have increased oxidative stress as evidenced by a reduction in liver vitamin E.

Changes in cross-fostered Sprague-Dawley rat litters exposed to perchlorate.

Ammonium perchlorate is used as an oxidizer in rocket fuel. It has become a groundwater contaminant, dissociating to ammonium cation and perchlorate anion. The perchlorate ion competes with iodide for uptake into the thyroid, reducing thyroid hormone production. Pregnant Sprague-Dawley rats were given either untreated or perchlorate (1 mg/kg-day) treated drinking water beginning on gestation day 2. One set of control and exposed dams was sacrificed on gestation day 20. The litters from the second set of control and exposed dams were crossed immediately after parturition and were sacrificed at postnatal day 10. Dam serum and thyroid, pooled fetal sera, and male and female pup sera were collected and analyzed for perchlorate, thyroid-stimulating hormone (TSH), triiodothyronine (T(3)), and thyroxine (T(4)). Control pups receiving perchlorate through lactation had serum levels at postnatal day 10 of 0.54 microg/ml and 0.56 microg/ml for male and female pups, respectively, whereas exposed fetuses had serum perchlorate levels of 0.38 +/- 0.04 microg/ml. Female pups receiving perchlorate lactationally had significantly lower levels of serum T(4) than control pups and prenatally exposed pups. Serum T(4) levels in male pups were not affected by perchlorate. Serum thyroid hormone levels from gestational perchlorate exposure were restored to control values by postnatal day 10. In utero perchlorate-exposure decreased serum T(4) levels in the fetus. Gestational studies in conjunction with a cross-fostering study design helped discern thyroid hormonal changes caused by perchlorate exposure during the perinatal period.

Vaccination of pregnant dams with intimin(O157) protects suckling piglets from Escherichia coli O157:H7 infection.

Cattle are important reservoirs of enterohemorrhagic Escherichia coli (EHEC) O157:H7 that cause disease in humans. Both dairy and beef cattle are asymptomatically and sporadically infected with EHEC. Our long-term goal is to develop an effective vaccine to prevent cattle from becoming infected and transmitting EHEC O157:H7 to humans. We used passive immunization of neonatal piglets (as a surrogate model) to determine if antibodies against EHEC O157 adhesin (intimin(O157)) inhibit EHEC colonization. Pregnant swine (dams) with serum anti-intimin titers of < or =100 were vaccinated twice with purified intimin(O157) or sham-vaccinated with sterile buffer. Intimin(O157)-specific antibody titers in colostrum and serum of dams were increased after parenteral vaccination with intimin(O157). Neonatal piglets were allowed to suckle vaccinated or sham-vaccinated dams for up to 8 h before they were inoculated with 10(6) CFU of a Shiga toxin-negative (for humane reasons) strain of EHEC O157:H7. Piglets were necropsied at 2 to 10 days after inoculation, and intestinal samples were collected for determination of bacteriological counts and histopathological analysis. Piglets that ingested colostrum containing intimin(O157)-specific antibodies from vaccinated dams, but not those nursing sham-vaccinated dams, were protected from EHEC O157:H7 colonization and intestinal damage. These results establish intimin(O157) as a viable candidate for an EHEC O157:H7 antitransmission vaccine.

Mass spectrometric determination of p-nonylphenol metabolism and disposition following oral administration to Sprague-Dawley rats

Isomers of 4-nonylphenol (NP), which are important industrial compounds and environmental breakdown products from widely used surfactants, have estrogenic activity in vitro and in vivo that has prompted interest in its potential for modulation of endocrine function in humans and wildlife. Mass spectrometry was used to quantify NP and metabolites in serum and endocrine-responsive tissues from dietary exposure in Sprague-Dawley rats. Tissue accumulation of NP aglycone was observed despite the predominance of glucuronidation in blood. Serum toxicokinetics of total NP, measured following gavage administration, showed rapid absorption and elimination (average half-times 0.8 and 3.5 h, respectively). NP was similarly administered by gavage to pregnant dams and total and aglycone NP were measured in dam serum and fetuses to show placental transfer into serum and brain. These data provide a basis for future correlations of biologic effects observed following dietary exposure in rats with those predicted from environmental exposures to humans.

Variations in Metallothionein, Zn, Cu, and Fe Concentrations and Ceruloplasmin Activity in Pregnant Rat Dams and Their Fetuses

Growing rat fetuses have great need for Zn, Cu, and Fe. In fetal livers (FL) large accumulations of Zn and Cu connected with increased metallothionein (MT) synthesis take place. In dams, serum changes in metals concentrations with increased ceruloplasmin (Cp) activity are observed. The aim of this study was to determine (1) mutual relationships in the accumulation of MT, Zn, Cu, and Fe in fetal livers; (2) changes in Zn, Cu, and Fe concentrations in dam serum; and (3) the day with the maximum Cp activity. Sections of rat dams were taken on 16th–21st day of gestation, twice a day, and MT, Zn, Cu, and Fe concentrations in liver, spleen, kidneys, and placenta of dams and in liver and brain in fetuses were determined. In fetal livers high correlations between MT and Zn and between Zn and Cu were obtained. The investigated Cp activity was always high, reaching its maximum on the 20th day and minimum on the 21st day. Significant correlation between Cp activity and Cu concentration in dam serum was also revealed. In conclusion it is suggested that Zn accumulation in FL is strictly connected with MT synthesis but Cu content in FL is rather dependent on Cp activity in dam serum. Iron accumulation in fetal livers is connected with the diminution of iron concentrations in dam serum.

Prolactin and growth hormone stimulation of lactation in mice requires thyroid hormones.

This experiment tested the hypothesis that thyroid hormones are essential for a milk production response to growth hormone (GH) and prolactin (PRL). Prior to breeding, female transgenic mice expressing the herpes simplex type-I thymidine kinase in the thyroid were treated with ganciclovir to ablate thyroid follicular cells. To provide for normal gestation, thyrocyte-ablated mice were supplied thyroxine (T4) in drinking water (0.2 microgram/ml) until 7 days before parturition. Litter size was adjusted to 9 pups, hormone administration began on Day 2 of lactation, and mice were sacrificed on Day 12. There were 5-6 mice in each of 7 treatments that included nonablated controls, thyrocyte-ablated controls, and thyrocyte-ablated mice treated with T4, GH, PRL, GH + T4, and PRL + T4. Thyroxine was administered in drinking water, and GH and PRL (20 microgram/d) were administered by subcutaneous injection. Compared with thyrocyte-ablated controls, litter weight gain was unaffected when dams were treated with GH, PRL, or T4 alone. However, when dams were treated with GH or PRL in combination with T4, litter weight gain increased 13% compared with thyrocyte-ablated controls and 18% compared with GH or PRL-treated mice. Concentration of T4 in serum of pups averaged 62 ng/ml and did not differ among treatments. Concentration of T4 in serum of dams averaged 76 ng/ml when T4-treated. Thyroxine 5'-deiodinase (5'D), the enzyme that converts T4 to triiodothyronine, was quantitated in liver, kidney, and mammary gland. Quantity of 5'D was lower in liver and kidney of thyrocyte-ablated dams without T4 than in respective tissues of mice treated with T4, and there was no effect of GH or PRL. However, in mammary gland, 5'D was increased by treatment with GH, PRL, or T4. Data show that thyroid hormones are necessary for a galactopoietic response to GH and PRL and demonstrate a unique organ-specific regulation of 5'D by galactopoietic hormones.

Haematology and serum chemistry parameters of the pregnant rat.

This study describes the baseline haematology and serum chemistry values found in non-pregnant, pregnant (gestational days [GD] 2-21) and lactating (postnatal days 1-9) Sprague Dawley rats (n = 3-10/day) from the NCTR breeding colony of Crl:COBS CD(SD)BR strain. Maternal body weights on GD0 ranged from 250 to 300 g. Multiple analytes were measured in both whole blood and serum of dams. Amniotic fluid, fetal serum, and postnatal pup serum analyte values were also acquired. Maternal blood was collected from the heart under subterminal carbon dioxide (CO2) anaesthesia. Most pregnant dam blood values were not appreciably different from values for non-pregnant dams until near term; near-term values for some analytes (red blood cells, haemoglobin, haematocrit, mean corpuscular haemoglobin concentration, alkaline phosphatase, albumin, total protein, glucose, total bilirubin, sodium, and chloride) decreased but returned to near-normal values soon after delivery. The most dramatic change was a three-fold elevation of serum triglyceride levels near term with a subsequent decrease at birth. Most serum chemistry analytes measured in progeny increased after birth except for alkaline phosphatase, calcium and potassium levels which decreased.

ビタミンE連日または間歇給与周産期乳牛における初乳および新生子牛血清中のビタミンE濃度

Vitamin-E supplements were administered to cows in the periparturient period either daily (2, 000IU/dose) or twice weekly (7, 000IU/dose). Fourteen cows were divided into the following groups: 1) controls (n=5); 2) cows given vitamin-E supplements daily (n=5); and 3) cows given vitamin-E supplements intermittently (n=4). Comparisons were made of vitamin-E concentrations in the dam, the serum of their one-week-old calves, and the dam colostrum. Vitamin-E levels in colostrum were measured within 24 hours after parturition and in calf serum seven days after birth. The levels were significantly higher in both colostrum and calf serum in the group to which Vitamin-E supplements had been administered daily. Consequently, since they maintain high vitamin-E concentration levels in the dam's serum, daily supplements are useful in ensuring effective transmission of vitamin E to the calf by way of the colostrum.

Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat.

Asian women consuming a traditional diet high in soy have a low incidence of breast cancer, yet when they emigrate to the USA the second but not the first generation lose this protection. Accordingly, we hypothesized that early exposure to genistein, a major component of soy, could have a permanent protective effect against breast cancer. Sprague-Dawley CD rats were exposed to genistein from conception to day 21 post-partum in the diet at concentrations of 0, 25 and 250 mg genistein/kg AIN-76A diet. At day 50 post-partum, all animals were treated with 80 mg dimethylbenz[a]anthracene/kg body wt to induce mammary cancers. Dietary genistein resulted in dose-dependent protection against development of mammary tumors (fewer tumors per rat). Analysis of mammary whole mounts showed that 21- and 50-day-old female rats had fewer terminal end buds, terminal ductal structures that were undifferentiated and were most susceptible to carcinogenesis. Bromodeoxyuridine incorporation studies revealed that dietary perinatal genistein resulted in a smaller proliferative compartment for terminal end buds. In rats fed the high genistein dose (250 mg/kg diet) total genistein concentrations in the serum and milk of dams 7 days postpartum were 418+/-198 and 137 pmol/ml, respectively. Total genistein concentrations in stomach milk, serum and mammary glands of 7-day-old offspring were 4439+/-1109 and 726 pmol/ml and 440+/-129 pmol/g, respectively. Total genistein concentrations in the serum and mammary glands of 21-day-old offspring were 1810+/-135 pmol/ml and 370+/-36 pmol/g, respectively. Dietary perinatal genistein did not cause significant toxicity in F0 and F1 females. We conclude that genistein in the diet at 'physiological levels' enhances cell differentiation, resulting in programming of mammary gland cells for reduced susceptibility to mammary cancer, with no observed toxicity to the reproductive tract of F1 females.