Developmental Sensitivity to the Induction of Great Vessel Malformations by N‐(2‐Aminoethyl)ethanolamine

N‐(2‐Aminoethyl)ethanolamine (AEEA) induced malformations of the great vessels in the offspring of rats treated during gestation and early lactation (Schneider et al., 2012. Birth Defects Res B Dev Reprod Toxicol [in press]). The aim of this study was to determine if in utero exposure alone was sufficient to induce these malformations or whether a peri‐postnatal exposure or physiological component was required. Three groups of five time‐mated female Wistar Han rats were administered AEEA (250 mg/kg/day) by gavage from gestation day (GD) 6 to GD 19 (groups 1 and 2) or from GD 6 to postnatal day 3 (group 3). Animals were euthanized on GD 21 (group 1) or postnatal day 4 (groups 2 and 3), and the hearts of the offspring were examined for changes to the great vessels. The incidence of malformations in group 1 was 91.1%, and primarily consisted of high aortic arch and abnormal carotid course. One fetus had an aortic aneurysm. All fetuses in groups 2 and 3 were malformed, primarily exhibiting abnormal carotid course and aneurysms, which mainly affected the aorta, ductus arteriosus, and pulmonary trunk. The incidence of high aortic arch was lower relative to group 1. Aneurysms were more prevalent in group 3 compared to group 2. These findings indicate that exposure to AEEA during gestation alone was sufficient to induce malformations of the great vessels and aneurysms, which may be triggered by physiological changes that occur during or after birth, but that the critical period of susceptibility to AEEA‐induced aneurysms in the rat extends beyond gestation into the early postnatal period.     

A comparison of the effects of prenatal exposure of CD‐1 mice to three imidazolium‐based ionic liquids

BACKGROUND: Ionic liquids (ILs; salts with melting points below 100°C) exhibit wide liquid ranges, non‐flammability, and thermal stability among other properties. These unique salts are best known as “green” alternatives to traditional volatile organic solvents, which are utilized in both academia and industry. Our current study compares the developmental toxicity potential of three representative ionic liquids, with various chain lengths: 1‐ethyl‐3‐methylimidazolium chloride ([C₂mim]Cl), 1‐butyl‐3‐methylimidazolium chloride ([C₄mim]Cl), and 1‐decyl‐3methylimidazolium chloride ([C₁₀mim]Cl). METHODS: From gestation days (GD) 6‐16, mated CD‐1 mice were orally dosed with one of the following: 1,000, 2,000, or 3,000 mg/kg/day [C₂mim]Cl; 113, 169, or 225 mg/kg/day [C₄mim]Cl; 50, 75, or 100 mg/kg/day [C₁₀mim]Cl; or the vehicle only. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: Fetal weight was significantly decreased in the two highest dosage groups exposed to [C₄mim]Cl and [C₁₀mim]Cl in comparison with their controls, but the [C₂mim]Cl treated groups were not affected. An apparent teratogenic effect was associated with both [C₄mim]Cl and [C₁₀mim]Cl, as the offspring exhibited certain uncommon morphological defects. However, the incidences of malformations were low and no correlation between incidence and dosage could be made. No morphological defects were observed in any of the [C₂mim]Cl‐treated groups, despite maternal morbidity at the highest dosage level. CONCLUSIONS: This study indicates that [C₄mim]Cl and [C₁₀mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium‐based ILs is influenced by alkyl chain length. Birth Defects Res (Part B) 89:233–238, 2010. © 2010 Wiley‐Liss, Inc.     

Toxicokinetic Profile of N‐(2‐Aminoethyl)ethanolamine in the Female Wistar Rat and Distribution into the Late Gestation Fetus and Milk

N‐(2‐aminoethyl)ethanolamine (AEEA) caused aneurysms of the great vessels in rats exposed in utero and during the first days post partum, exacerbated by postnatal treatment of the lactating dams (Moore et al., 2012. Birth Defects Res B Dev Reprod Toxicol [95:116‐122]). The purpose of this work was to examine the systemic availability of AEEA during gestation and early lactation. The absorption of AEEA was determined following oral administration to nonpregnant and pregnant female Wistar rats. A single dose administered by gavage (0.5 or 50 mg/kg) on gestation day 18 was rapidly and extensively (>90%) absorbed from the gastrointestinal tract (absorption t_1/2 = 0.1–0.2 hr). Elimination from the plasma followed a biphasic pattern, with a rapid elimination phase (t_1/2 α = 1.6–1.8 hr) followed by a slower phase (t_1/2 β = 16.7–17.3 hr). Following repeated gavage administration during gestation day 17 to 19, ¹⁴C‐AEEA–derived radioactivity readily partitioned into the fetus and was evenly distributed therein, but cleared approximately twofold slower from the fetal blood and tissues than the maternal blood and chorioallantoic placenta. When administered to lactating dams during lactation days 1 to 12, ¹⁴C‐AEEA–derived radioactivity preferentially partitioned into the milk reaching levels that were between 1.6‐ and 2.5‐fold higher than the maternal blood. Although the concentration of AEEA equivalents in the maternal blood remained quite consistent, the concentration in the milk fell by almost 40% between lactation days 4 and 12, probably reflecting an increase in milk production over this same period. We confirm exposure of the offspring to AEEA both in utero and during lactation, but that AEEA does not appear to specifically concentrate in the great vessels.     

Resistance Training Preserves Fat‐free Mass Without Impacting Changes in Protein Metabolism After Weight Loss in Older Women

This study assessed the effects of resistance training (RT) on energy restriction–induced changes in body composition, protein metabolism, and the fractional synthesis rate of mixed muscle proteins (FSRm) in postmenopausal, overweight women. Sixteen women (age 68 ± 1 years, BMI 29 ± 1 kg/m², mean ± s.e.m.) completed a 16‐week controlled diet study. Each woman consumed 1.0 g protein/kg/day. At baseline (weeks B1–B3) and poststudy (weeks RT12–RT13), energy intake matched each subject's need and during weeks RT1–RT11 was hypoenergetic by 2,092 kJ/day (500 kcal/day). From weeks RT1 to RT13, eight women performed RT 3 day/week (RT group) and eight women remained sedentary (SED group). RT did not influence the energy restriction–induced decrease in body mass (SED ?5.8 ± 0.6 kg; RT ?5.0 ± 0.2 kg) and fat mass (SED ?4.1 ± 0.9 kg; RT ?4.7 ± 0.5 kg). Fat free mass (FFM) and total body water decreased in SED (?1.6 ± 0.4 and ?2.1 ± 0.5 kg) and were unchanged in RT (?0.3 ± 0.4 and ?0.4 ± 0.7 kg) (group‐by‐time, P ≤ 0.05 and P = 0.07, respectively). Protein–mineral mass did not change in either group (SED 0.4 ± 0.2 kg; RT 0.1 ± 0.4 kg). Nitrogen balance, positive at baseline (2.2 ± 0.3 g N/day), was unchanged poststudy. After body mass loss, postabsorptive (PA) and postprandial (PP) leucine turnover, synthesis, and breakdown decreased. Leucine oxidation and balance were not changed. PA and total (PA + PP) FSRm in the vastus lateralis were higher after weight loss. RT did not influence these protein metabolism responses. In summary, RT helps older women preserve FFM during body mass loss. The comparable whole‐body nitrogen retentions, leucine kinetics, and FSRm between groups are consistent with the lack of differential protein–mineral mass change.     

三聚氰胺泌尿系统结石大鼠模型的研究

目的观察工业原料三聚氰胺连续给药诱发SD大鼠尿结石的成模情况。方法60日龄SPF级SD大鼠130只,雌雄各半,体质量（200＋24）g,随机分为给药5个组和空白对照组各20只,溶媒对照组10只。给药组分别给予三聚氰胺0．05、0．1、0．2、0．3、0．4g／（kg·d）连续灌胃;溶媒对照组灌胃10g／L甲基纤维素蒸馏水2mL／（只·d）,空白对照组灌胃无菌水2mL/（只·d）。采用体视显微镜观察大鼠肾脏、输尿管和膀胱形态改变,比较各组肾脏、膀胱的质量和脏器指数,观察大鼠CREA、BUN、UA、Ca、P、Mg含量变化。结果0．4g／kg组给药20d,0．2、0．4g／kg组给药30d,肌酐高于空白对照组;0．4g/kg组给药30d,尿素氮、尿酸高于空白对照组。给药20d各组血钙、磷、镁均偏低。给药30d,0．05、0．2、0．3、0．4g／kg组左肾质量比空白对照组增加。各组肾脏大小、颜色均与正常对照组比较接近,未见结石和明显黄色沉淀物,但有部份肾脏在皮、髓质交界处有点状或片状出血灶。输尿管未见结石。部分膀胱粘膜充血,部分雄性大鼠出现膀胱结石,其中给药20d各组雄性大鼠出现率为52％（13／25）,30d各组出现率为56％（14／25）,膀胱结石颜色多为淡黄色混合白色、白色。结论（0．05～0．4）g/kg三聚氰胺连续给药30d,对肾脏损害轻微,可诱发雄性大鼠产生膀胱结石。     

Chemoprophylactic studies with ivermectin against subperiodic Brugia malayi infection in the leaf monkey, Presbytis cristata

Four Presbytis cristata were treated with oral ivermectin at the same time as the subcutaneous inoculation of 100 infective larvae monthly for three months. Two animals given 0.2 mg/kg monthly and two others given 0.3 mg/kg monthly as well as three control animals became patent for microfilaraemia. However, only 1% of the infective dose was recovered as adult worms from animals in the higher drug dosage group compared to 8.2% and 6.2% in the lower dosage and control groups respectively.     

Lack of a co‐promotion effect of 60 Hz circularly polarized magnetic fields on spontaneous development of lymphoma in AKR mice

The present study was conducted to investigate the possible effect of 60 Hz circularly polarized magnetic fields (MFs) as promoters of genetically initiated lymphoma in AKR mice. One hundred sixty female animals were divided into four different groups. They were exposed to four different intensities of circularly polarized MFs. Animals received exposure to 60 Hz circularly polarized MF at field strengths (rms‐value) of 0 µT (sham control, T1, Group I), 5 µT(T2, Group II), 83.3 µT (T3, Group III), or 500 µT(T4, Group IV), for 21 h/day from the age of 4–6 weeks to the age of 44–46 weeks. There were no exposure‐related changes in mean survival time, clinical signs, body weights, hematological values, micronucleus assay, gene expression arrays, analysis of apoptosis, and necropsy findings. At histopathological examination, lymphoma was seen in all the groups. The tumor incidence was 31/40(78%), 30/40(75%), 32/40(80%), and 31/40(78%) in sham control, 5, 83.3, and 500 µT groups, respectively. However, there were no differences in the tumor incidence between the sham control (T1) and circularly polarized MF exposure groups (T2–T4). In conclusion, there was no evidence that exposure to 60 Hz circularly polarized MF strengths up to 500 µT promoted lymphoma in AKR mice. Bioelectromagnetics 31:130–139, 2010. © 2009 Wiley‐Liss, Inc.     

An Enhanced Pre‐ and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody

Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B‐cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16–19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and infants included clinical signs, body weight, toxicokinetics, blood lymphocyte phenotyping, T‐cell‐dependent antibody response (infants only), antitherapeutic antibody (ATA), organ weights (infants only), and gross and microscopic histopathology. Infants were also examined for external and visceral morphologic and neurobehavioral development. There were no adverse tabalumab‐related effects on maternal or infant endpoints. An expected pharmacological decrease in peripheral blood B‐lymphocytes occurred in adults and infants; however, B‐cell recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204 in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T‐cell‐dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary immunization. Following secondary KLH immunization, all infants in both dose groups mounted anti‐KLH IgM and IgG antibody responses similar to control. Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the no‐observed‐adverse‐effect level for maternal and developmental toxicity was 30 mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety of 16× the anticipated clinical exposure.     

Paternity in wild ring‐tailed lemurs (Lemur catta): Implications for male mating strategies

In group‐living species with male dominance hierarchies where receptive periods of females do not overlap, high male reproductive skew would be predicted. However, the existence of female multiple mating and alternative male mating strategies can call into question single‐male monopolization of paternity in groups. Ring‐tailed lemurs (Lemur catta) are seasonally breeding primates that live in multi‐male, multi‐female groups. Although established groups show male dominance hierarchies, male dominance relationships can break down during mating periods. In addition, females are the dominant sex and mate with multiple males during estrus, including group residents, and extra‐group males—posing the question of whether there is high or low male paternity skew in groups. In this study, we analyzed paternity in a population of wild L. catta from the Bezà Mahafaly Special Reserve in southwestern Madagascar. Paternity was determined with 80–95% confidence for 39 offspring born to nine different groups. We calculated male reproductive skew indices for six groups, and our results showed a range of values corresponding to both high and low reproductive skew. Between 21% and 33% of offspring (3 of 14 or three of nine, counting paternity assignments at the 80% or 95% confidence levels, respectively) were sired by extra‐troop males. Males siring offspring within the same group during the same year appear to be unrelated. Our study provides evidence of varying male reproductive skew in different L. catta groups. A single male may monopolize paternity across one or more years, while in other groups, >1 male can sire offspring within the same group, even within a single year. Extra‐group mating is a viable strategy that can result in extra‐group paternity for L. catta males.     

The Potential of Cr3 [Triaqua‐μ3‐Oxo‐Hexa‐μ‐Propionatotrichromium(III) Chloride] to Reduce Birth Defects in the Offspring of Diabetic CD‐1 Mice

Diabetes mellitus is a growing concern worldwide and leads to multiple complications during pregnancy. Pharmacologic doses of chromium (Cr) have been linked with improving insulin sensitivity and other positive benefits in the treatment of diabetes in animal models. By using streptozotocin induced hyperglycemia in female CD‐1 mice, reproductive outcomes of diabetic and chromium‐dosed diabetic females were examined. After dosing 10 mg/kg Cr in the form of triaqua‐μ₃‐oxo‐hexa‐μ‐propionatotrichromium(III) chloride or Cr3 during gestation days 8–16 (GD8–GD16), all females were sacrificed on gestation day 17 (GD17) and examined for maternal weight gain. The fetuses were examined for gross malformations and for skeletal malformations. The offspring of Cr3‐dosed females tended to have a reduction in the incidence of supernumerary ribs. While hyperglycemia still had negative impacts on the health of dams and their offspring, administration of Cr led to an apparent trend in the reduction in the number of malformations and incidence of supernumerary ribs compared to those of untreated diabetic mothers     

The influence of sodium metavanadate on the process of diabetogenesis in BB rats

Vanadium has been shown to be beneficial in the oral treatment of animal models of type 1 and type 2 diabetes. The aim of the study was to evaluate the short-term effects of sodium metavanadate in prediabetic BB-DP rats. To do this, 96 rats were divided into 4 equal groups. Groups VI, V2, V3 were treated with sodium metavanadate (0.1, 0.2 and 0.3 mg/ml respectively) and sodium chloride (0.5 mg/ml) in drinking water for 7 days. Group C received only sodium chloride (0.5 mg/ml). Blood glucose (BG), glycosuria, ketonuria, body weight and insulinemia were determined. The age of onset of diabetes was significantly higher for groups V2, V3 compared to group C, (p < 0.05) and depends on the metavanadate concentration (V3 vs. V1, p=0.006). The incidence of diabetes was lower in the rats treated with metavanadate than in the control group, but this difference was not statistically significant. In diabetic rats, the BG at the onset was higher in group C than in groups V, p < 0.05. Insulinemia, at the onset of the treatment as well as immediately after its cessation showed a drop in the treatment groups, proportionally to the dosage of vanadium, but later increased slowly and continuously until the end of the experiment. In conclusion, metavanadate delays the development of diabetes in BB-DP rats, but does not prevent its onset. A milder form of diabetes occurs in diabetic rats treated with metavanadate. The effects depend on the metavanadate concentration and 0.2 mg/ml is preferable.     

When genes move farther than offspring: gene flow by male gamete dispersal in the highly philopatric bat species Thyroptera tricolor

For species characterized by philopatry of both sexes, mate selection represents an important behaviour for inbreeding avoidance, yet the implications for gene flow are rarely quantified. Here, we present evidence of male gamete‐mediated gene flow resulting from extra‐group mating in Spix's disc‐winged bat, Thyroptera tricolor, a species which demonstrates all‐offspring philopatry. We used microsatellite and capture–recapture data to characterize social group structure and the distribution of mated pairs at two sites in southwestern Costa Rica over four breeding seasons. Relatedness and genetic spatial autocorrelation analyses indicated strong kinship within groups and over short distances (<50 m), resulting from matrilineal group structure and small roosting home ranges (~0.2 ha). Despite high relatedness among‐group members, observed inbreeding coefficients were low (F_IS = 0.010 and 0.037). Parentage analysis indicated mothers and offspring belonged to the same social group, while fathers belonged to different groups, separated by large distances (~500 m) when compared to roosting home ranges. Simulated random mating indicated mate choice was not based on intermediate levels of relatedness, and mated pairs were less related than adults within social groups on average. Isolation‐by‐distance (IBD) models of genetic neighbourhood area based on father–offspring distances provided direct estimates of mean gamete dispersal distances () > 10 roosting home range equivalents. Indirect estimates based on genetic distance provided even larger estimates of , indicating direct estimates were biased low. These results suggest extra‐group mating reduces the incidence of inbreeding in T. tricolor, and male gamete dispersal facilitates gene flow in lieu of natal dispersal of young.     

Quality–quantity trade‐off of human offspring under adverse environmental conditions

A central paradigm in life‐history theory is the trade‐off between offspring number and quality. Several studies have investigated this trade‐off in humans, but data are inconclusive, perhaps because prosperous socio‐cultural factors mask the trade‐off. Therefore, we studied 2461 offspring groups in an area under adverse conditions in northern Ghana with high fertility and mortality rates. In a linear mixed model controlling for differences in age and tribe of the mother and socioeconomic status, each additional child in the offspring group resulted in a 2.3% (95% CI 1.9–2.6%, P < 0.001) lower proportional survival of the offspring. Furthermore, we made use of the polygamous population structure and compared offspring of co‐wives in 388 households, thus controlling for variation in resources between compounds. Here, offspring survival decreased 2.8% (95% CI 2.3–4.0%, P < 0.001) for each increase in offspring number. We interpret these data as an apparent quality–quantity trade‐off in human offspring.     

Manganese exposure alters the expression of N‐methyl‐d‐aspartate receptor subunit mRNAs and proteins in rat striatum

Manganese is one of the ubiquitous environmental pollutants that can induce an indirect excitotoxicity caused by altered glutamate (Glu) metabolism. The present study has been carried out to investigate the effect of Mn on the expression of N‐methyl‐d ‐aspartate receptor (NR) subunit mRNAs and proteins in rat striatum when rats were in manganism. The rats were divided randomly into four groups of six males and six females each: control group (group 1) and 8, 40, and 200 μmol/kg Mn‐treated groups (groups 2–4). The control group rats were subcutaneously (s.c.) injected with normal saline. Manganese‐treated rats were s.c. injected with respectively 8, 40, and 200 μmol/kg of MnCl₂ · 6H₂O in normal saline. The administration of MnCl₂ · 6H₂O for 4 weeks significantly increased Mn concentration in the striatum. With the increase in administered MnCl₂ dosage, Glu concentration and cell apoptosis rate increased significantly. The relative intensity of NR2A mRNA decreased significantly in 8 μmol/kg Mn‐treated rats. However, relative intensities of NR1 and NR2B mRNAs decreased significantly in 40 μmol/kg Mn‐treated rats. Similarly, the relative intensity of NR2A protein showed a significant decrease in 40 μmol/kg Mn‐treated rats whereas those of NR1 and NR2B decreased significantly in 200 μmol/kg Mn‐treated rats. Therefore, the expression of NR2A mRNA and protein were much more sensitive to Mn than that of NR1 and NR2B. In conclusion, the results suggested that Mn induced nerve cell damage by increasing extracellular Glu level and altered expression of NR subunit mRNAs and proteins in rat striatum. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:1–9, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20306     

Short‐term exposure to a 1439‐MHz TDMA signal exerts no estrogenic effect in rats

The aim of this study was to elucidate the possible effects of short‐term exposure to a 1439‐MHz electromagnetic field (EMF) employing time division multiple access (TDMA), which is the basis of the Japanese Personal Digital Cellular system, on estrogenic activity in rats. Sixty‐four ovariectomized female Sprague–Dawley rats were divided into four groups: EMF exposure (EM), sham exposure, cage control, and 17 beta‐estradiol injected (E2). The EM group was exposed, for 4 h per day on three consecutive days, to the 1439‐MHz TDMA signal that produced 5.5–6.1 and 0.88–0.99 W/kg average specific absorption rates in the brain and the whole body, respectively. The uterine wet mass and serum estradiol level significantly increased in the E2 group, while there were no differences among the other three groups. Although negative effects of long‐term EMF exposure must be thoroughly investigated before a final conclusion can be reached, our results do not support the assumption that the high frequency EMF used in cellular phones exerts estrogenic activity. Bioelectromagnetics 31:573–575, 2010. © 2010 Wiley‐Liss, Inc.     

Assessing genetic identity of sporophytic offspring of the brown alga Undaria pinnatifida derived from mono‐crossing of gametophyte clones by use of amplified fragment length polymorphism and microsatellite markers

The haploid stage of gametophytes of the subtidal brown alga Undaria pinnatifida can be vegetatively propagated under favorable conditions. This unique characteristic makes it possible to establish independent gametophyte cell lines that are zoospore‐derived. Sporophytic offspring can be generated through hybridizing the male and female gametophytes, which are derived from different cell lines. Accumulated experiences in this and other species in Laminariales demonstrated the applicability of this novel way to breed desired strains for open‐sea cultivation. Sporophytic offspring originated from mono‐crossing of male and female gametophyte clones were shown to have similar morphological characteristics under identical ambient conditions. However, there has been no report to relate this similarity on molecular levels. In this report, amplified fragment length polymorphism (AFLP) and microsatellite markers were used to analyze the genetic identity of sporophytic offspring of U. pinnatifida originated from two mono‐crossing lines (M1 and M2), two self‐breeding lines (S1 and S2) and one wild population (W). Totally 318 AFLP loci were revealed by use of 11 primer sets, of which 4.7%, 0.3%, 17.9%, 16.4% and 36.5% were polymorphic in M1, M2, S1, S2 and W, respectively. The pairwise genetic identity among the individuals of the same line was assessed. It was shown that offspring from mono‐crossing lines had a higher degree of identity (95.6–100%) than self‐breeding lines (87.7–98.4%) and the wild population (81.5–92.1%). Analysis by use of six microsatellite loci also revealed a higher genetic identity among individuals of the mono‐crossing line, further confirming the results of AFLP analysis. Results from this investigation support, on molecular levels, the novel way to produce and maintain strains in U. pinnatifida by use of different gametophyte cell lines.     

Cut‐points for Waist Circumference in Europids and South Asians

There is little strong evidence that currently recommended higher waist circumference cut‐points for Europids compared with South Asians are associated with similar risk for type 2 diabetes. This study was designed to provide such evidence. Longitudinal studies over 5 years were conducted among 5,515 Europid and 2,214 ethnically South Asian participants. Age‐standardized diabetes incidence at different levels of waist circumference and incidence difference relative to a reference value were calculated. The Youden Index was used to determine waist circumference cut‐points. At currently recommended cut‐points, estimated annual diabetes incidence for a 50‐year‐old Europid was <0.6% for both sexes, and for a 50‐year‐old South Asian, 5.8% for men and 2.1% for women. Annual diabetes incidence of 1% was observed for a 50 year old at a waist circumference 35–40 cm greater in Europid compared to South Asian men and women. Incidence difference between recommended cut‐points and a reference value (80 cm in men, 70 cm in women) was 0.3 and 4.4% per year for Europid and South Asian men, and 0.2 and 0.8% per year for Europid and South Asian women, respectively. Waist circumference cut‐points chosen using the Youden Index were shown to be dependent on obesity levels in the population. The much higher observed risk of diabetes in South Asians compared to Europids at the respective recommended waist circumference cut‐points suggests that differences between them should be greater. Approaches that use the Youden Index to select waist circumference cut‐points are inappropriate and should not be used for this purpose.     

Maternal High‐Fat Diet Effects on Adaptations to Metabolic Challenges in Male and Female Juvenile Nonhuman Primates

Objective

This study aimed to determine whether maternal high‐fat diet (HFD) consumption in nonhuman primates alters the ability of offspring to adapt metabolically to nutrient and caloric challenges.

Methods

Offspring from Japanese macaque dams fed either a control (CTR) diet or HFD were weaned onto a CTR diet creating two groups: maternal HFD (mHFD, n = 18) and maternal CTR (mCTR) diet (n = 12). Male and female offspring were exposed to a 5‐day 30% calorie restriction and to a 35‐day HFD challenge (HFDC), at 16 and 24 months of age, respectively. Caloric intake, body weight, and energy expenditure were measured.

Results

Offspring from both groups showed similar body weight, food intake, and metabolic adaptations to a 5‐day calorie restriction. mHFD offspring demonstrated increased food intake and early weight gain in response to a 35‐day HFDC; however, group differences in weight dissipated during the challenge. Unlike mCTR animals, the mHFD group had a significant increase in fasting insulin after acute HFD exposure.

Conclusions

The current findings indicate that offspring exposed to an mHFD show metabolic adaptations to calorie restriction that are largely similar to those of offspring exposed to a mCTR diet but show delayed adaptation upon exposure to an acute HFDC.

     

Effects of gestational exposure to 1.95‐GHz W‐CDMA signals for IMT‐2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats

The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95‐GHz wide‐band code division multiple access (W‐CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT‐2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7–17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole‐body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243–271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses. Bioelectromagnetics 30:205–212, 2009. © 2008 Wiley‐Liss, Inc.     

Timing of the first cleavage post‐insemination affects cryosurvival of in vitro–produced bovine blastocysts

The time of the first cleavage of bovine zygotes during in vitro culture can affect the rate of development and cell number of the blastocysts. The aim of this work was to study the effect of the timing of first cleavage on the cryosurvival of the resulting blastocysts. Following standard IVM and IVF, zygotes were cultured in modified synthetic oviduct fluid (SOF), with 10% fetal calf serum (FCS) added 48 hr post insemination, in a humidified atmosphere of 5% CO_2, 5% O₂ and 90% N₂. Embryos which cleaved by 24, 27 30, 33, or 36 hr after insemination (IVF) were harvested and further cultured to the blastocyst stage (day 7 or day 8 post IVF). All developing blastocysts on days 7 and 8 were classified into three groups and were cryopreserved by vitrification. Group A consisted of blastocysts (<150 μm, small blastocysts); group B consisted of expanded or hatching blastocysts (>150 μm, large blastocysts); and group C consisted of morphologically poor quality blastocysts. The vitrification solution consisted of 6.5 M glycerol and 6% bovine serum albumin in PBS (VS3a). Thawed embryos were cultured further and survival was defined as the re‐expansion and maintenance of the blastocoel over 24, 48, and 72 hr, respectively. Overall survival and hatching at 72 hr post‐thawing was higher in blastocysts formed by day 7 than those formed by day 8 (60% vs. 40% survival; 63% vs. 45% hatching). Large blastocysts from day‐7 and day‐8 groups survived significantly better than small or poor quality blastocysts (76% vs. 63% and 31%; 72% vs. 30% and 26%, respectively; P < 0.05). Day‐7 blastocysts from the 27‐ and 30‐hr cleavage groups survived significantly better than those from the 36‐hr group (63% and 66% vs. 25%, P < 0.05). Day‐8 blastocysts from later cleaved (30 hr) zygotes had a higher survival than the 27‐hr cleavage groups (52% vs. 26%, P < 0.05). These results indicate that the day of blastocyst appearance, developmental stage, and timing of the first cleavage post‐insemination can influence the cryosurvival of bovine blastocysts following vitrification. Mol. Reprod. Dev. 53:318–324, 1999. © 1999 Wiley‐Liss, Inc.