Effects of preweaning nutrition on weight gain during pregnancy in mice

Previous work has shown that preweaning litter size affects the response of adult mice to dietary induced obesity, with animals reared in small litters showing increased hyperphagia and weight gain. The present work addressed whether a similar effect would be seen in the weight changes normally accompanying pregnancy and lactation. B6D2F2 mice were reared in small (4), medium (8) and large (12) litters. Adult females from each of these conditions were mated with males from medium litters and their body weight and food intake measured throughout pregnancy and lactation. Food intake increased during pregnancy and correlated with the dams' litter size, but the amounts consumed by all groups appeared similar. This was also true of maternal weight gain during pregnancy, pup weight and litter size. During lactation, the only differences were that animals which had been reared in large litters ate more food and weaned heavier pups than those in medium litters. These results differ from those previously obtained on dietary induced obesity, supporting different regulatory mechanisms in the two conditions.     

Relationship between litter size and the development of the rat brain during the suckling period

The brain of 23-day-old rats raised in small, large, and control litters is studied. In large litters, body weight is significantly lower and the relative mass of the brain is higher than in controls. In small litters, body weight of males and females is considerably higher, while the relative mass of the brain is lower; in females, the absolute mass of the brain and of the left hemisphere is significantly higher. In rats of both sexes from small litters the weight of body, brain, and hemisphere is higher than in rats from large litters. In addition, in males from small litters the neurons of layer V are larger. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 582–584, May, 1996     

Male and female 5-HT(1B) receptor knockout mice have higher body weights than wildtypes.

5-HT(1B) receptors have a regulatory role in serotonergic activity and influence feeding behavior and body weight. Because the absence of 5-HT(1B) receptors may cause changes in this regulation, body weight was measured in male and female 5-HT(1B) receptor knockout (5-HT(1B) KO) and wildtype (WT) mice from weaning until the age of 30 weeks. In both genders, 5-HT(1B) KO mice had a higher body weight than WT mice (17% and 9%, respectively). Body weight was significantly higher for males over the entire period and for females from Week 18 onwards. Absolute food and water consumption were related to body weight. However, relative to body weight, males consumed more than females. 5-HT(1B) KO males drank strikingly more water. Housing mice singly reduced food and water intake in males, but not in females. Plasma leptin levels and most organ weights did not differ between genotypes, indicating that higher body weight in 5-HT(1B) KO mice is not related to obesity. Relative to body weight, brains and adrenals were larger in females, while heart and liver were smaller. Kidneys were smaller in females, but larger in 5-HT(1B) KO mice, while lungs showed opposite effects. Spleen and testes were smaller in 5-HT(1B) KO mice. Although 5-HT(1B) KO males are more aggressive, testosterone levels were not different from WT mice. Basal corticosterone levels were similar in all groups and increased in response to mild stress, particularly in females. Lifelong absence of 5-HT(1B) receptors in mice resulted in clear phenotypic differences in body weights and food and water intake. Lacking this receptor increases body growth, without signs of obesity. A potential genetic background effect influencing this phenotype is discussed.     

Cross-sectional area of the elephant corpus callosum: comparison to other eutherian mammals

The current study reports our findings of the relationship between cross-sectional area of the corpus callosum and brain mass in over 100 eutherian mammal species. We were specifically interested in determining whether the elephant had a corpus callosum the size that would be expected for eutherian mammal with a brain mass of approximately 5000 g, or whether a different morphology had evolved. To answer this question we first analysed data from primates, other eutherian mammals and cetaceans, finding that primates and other eutherian mammals showed a positive allometric relationship between the two variables, such that larger brains had a relatively larger corpus callosum. Interestingly, primates have a slightly larger corpus callosum than other eutherian mammals, but showed a similar allometric scaling to this group. The cetaceans had a both absolutely and relatively small corpus callosum compared to other mammals and showed isometric scaling with brain mass. The six elephants studied herein had the largest absolute corpus callosums recorded to date; however, relative to the mass of their brain, the size of the corpus callosum was what would be expected of a typical eutherian mammal with a brain mass of approximately 5000 g. The data for elephants hinted at sexual dimorphism in size of the corpus callosum, with female elephants having both an absolute and relatively larger callosum than the males. If this observation is supported in future studies, the elephants will be the first non-primate species to show sexual dimorphism in this neural character. The results are discussed in both an evolutionary and functional context.     

Successive resetting of the set point for target body size

Previous studies support the existence of a central set point for target body size. The set point is a hypothetical fixed reference for body size. The present experiments were carried out to determine whether target body size and, by implication, the putative set point can be consecutively reset or whether, once set by an extraneous factor, it is refractory to another extraneous factor. Male and female rats were given 6.0 Gy whole head X-irradiation at two days of age or were sham-irradiated as controls. Significant permanent reduction of body weight, tibia length, and pituitary weight resulted from head-irradiation in both males and females; gonad weight was reduced in males but not significantly in females. At 41 days of age the irradiated animals were injected sc with cortisone acetate, 1 mg/25 g body weight/day, or saline. During cortisone treatment the head-irradiated rats had a decrease in body weight velocity; the effect was greater in males than in females. Following treatment growth velocity approached normal in treated males, and slightly exceeded normal in treated females. Treated males had significantly reduced body weight, tail length, and tibia length at the end of the study. Treated females showed a similar pattern of body weight growth to the treated males, but there was not a significant long term reduction of body weight or change in tail length or tibia length. Final pituitary and gonad size was not affected by cortisone treatment in either sex. The results indicate that the reset of target size after head-irradiation does not result from damage to putative control.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of neonatal oil administration on brain weight of inbred and heterogeneous mice

A single injection of sesame oil on postnatal Day 4 reduced adult bain weight in male and female mice of the C3H/HeJ strain. The same neonatal treatment had no effect on brain weight of heterogeneous mice derived from a cross of 8 inbred strains. In agreement with previous findings in inbred strains, C3H/HeJ females were found to have larger brains than males. This difference between the genders was not seen in heterogeneous mice. The effect of neonatal oil administration on adult brain weight provides an additional example of the effect of neonatal manipulations on the adult organism and underscores the importance of adherence to appropriate control procedures in studies involving administration of hormones in early life, particularly when infant strains are used as experimental subjects.     

Genetic variation in the development of mouse brain and behavior: evidence from the middle postnatal period.

Six inbred strains and 3 F2 hybrid crosses of mice were assessed for developmental status at 32 days after conception (about 13 days after birth). Phenotypes measured included body weight, brain weight, maturity of 14 reflexive behaviors, myelination of 80 fiber tracts, and thickness of the external granular layer of the cerebellum. All measures of brain and behavior showed a similar pattern of results: hybrids were generally more advanced than either of their inbred parent strains; differences among inbred strains were large, but differences among hybrid crosses were quite small. Acceleration of F2 mice compared to their homozygous relatives ranged from .5 to 2.4 days mean difference. Developmental ages of inbred litters ranged from 28.7 to 32.2 days, whereas hybrid litters ranged from 31.5 to 32.7 days.     

The effects of rearing environment on pup development

Norway rats were reared either in a standard laboratory cage or in a nest constructed by the dam from newspaper strips. Growth, thermoregulatory ability, and adrenal, gonad, adipose tissue, and brain weights were measured at weaning on Day 21 postpartum. While there was no difference in growth, nest-reared animals had lower body temperatures, but could thermoregulate as well as cage-reared animals. Nest-reared animals also had relatively smaller adrenals and less brown adipose tissue. Gonad and brain weights were similar. An interesting finding was that males and females were differentially affected by the nest-rearing. Differences between cage- and nest-reared animals were more evident in females, and thermoregulatory ability was more closely associated with the quality of the nest during the first 10 days than body weight in females. For males, body weight was more important. These latter data are discussed in relation to differential interaction between the dam and male and female pups.     

Clastogenicity of diepoxybutane in bone marrow cells and male germ cells of mice

The bifunctional metabolite of 1,3-butadiene, 1,2:3,4-diepoxybutane(DEB), was tested in the mouse bone marrow micronucleus assayand in male mouse germ cell tests, namely the analysis of firstcleavage divisions and the dominant lethal assay. All experimentswere performed with single intraperitoneal treatment of theanimals. In the micronucleus test, DEB doses of 4.5, 9.0, 18.0and 36.0 mg/ kg body weight were tested at a sampling intervalof 24 h for bone marrow. The dose response for the inductionof micronuclei in polychromatic erythrocytes was linear withthe lowest effective dose of 9.0 mg/kg body weight No sensitivitydifference was observed between male and female mice. The cytogeneticanalysis of first cleavage division chromosomes was performedafter treatment of male mice with 17, 26, 34, 43 and 52 mg/kgbody weight of DEB and mating the males to hormonally stimulatedfemales on days 7, 14, 21 and 28 after treatment The two higherdoses caused general toxicity evidenced by the poor mating behaviorof the males. Only 13 and 20% of the mated females were fertilizedon day 7 after treatment of the males with 43 and 52 mg/kg bodyweight of DEB, respectively. An increased number of unfertilizedoocytes was obtained from fertilized females on day 7 aftertreatment of the males with 34 mg/kg body weight of DEB. Witha dose of 26 mg/kg body weight, it was demonstrated that chromosomalaberrations were only induced in spermatozoa (mating on day7 after treatment) while spermatids (mating on days 14 and 21)and spermatocytes (mating on day 28) were not susceptible tothe clastogenic effect of DEB. The response in spermatozoa inthe dose range 17–34 mg/kg body weight was linear up to26 mg/kg body weight and reached a plateau thereafter. The resultsof the dominant lethal experiments performed in the dose range18–54 mg/kg body weight gave results similar to the cytogeneticstudy. With the highest dose tested, the toxicity and cytotoxicityduring the first 8 mating days after treatment dramaticallyreduced the number of pregnant females and, consequently, thetotal implantations, so that no significant dominant lethaleffect could be assessed. During mating days 9–12 (treatedlate spermatids), a significant dominant lethal effect was observed.With the two lower doses (18 and 36 mg/kg body weight), thedominant lethal effect was restricted to spermatozoa. The goodcorrelation of the chromosomal aberrations with dominant lethalmutations confirms the chromosomal origin of dominant lethaleffects. The clastogenic effect of DEB in somatic cells andin germ cells of mice was of the same order of magnitude. ³To whom correspondence should be addressed     

Sonographic measurement of the spleen: splenic length in adults and its correlation with different parameters

Aim: The purpose of this study was to establish guidelines for normal splenic length at different ages by using a simple and reproducible sonographic method and to find out a relation between spleen length, age, height, weight, and surface area. Materials and methods: One hundred sixty subjects, from 21 years to 60 years old, had sonography because of abdominal and/or pelvic problems unrelated to the spleen. The splenic size was measured by obtaining a coronal view that included the hilum during deep inspiration to minimize masking by lung. The greatest longitudinal distance between the dome of the spleen and the tip (splenic length) was measured and correlated with age, height, and weight. Results: The results show that the splenic length decreased with increase in age in both males and females. The length of the spleen increased with increase in the body height, body weight, and body surface area in both males and females. In most of the subjects, the splenic length was found to be <11 cm. The splenic size in males was greater than that in females. Discussion: The findings of present study that the splenic length decreases with age are similar to the findings of Loftus and Metreweli. Konus et al in 1998 proposed that the splenic length correlated best with the body height. This is similar to the findings of the present study. The finding of present study that the splenic length has positive correlation with the body height, weight, and surface area is similar to the finding of Megremis et al. Conclusion: On the basis of the above study, it was concluded that the splenic length decreased with increase in age in both males and females. The length of the spleen has positive correlations with increase in the body height, body weight, and body surface area in both males and females. The splenic length was less in females than that in males with the corresponding age, body height, body weight, and body surface area. In most of the subjects, the splenic length was found to be <11 cm.     

Restoration of a normal reproductive lifespan after grafting of cryopreserved mouse ovaries

Fresh and frozen ovaries from 10 day old C57BL/6J-Gpi-1(a) mice were grafted orthotopically into ovariectomized B6CBF1 (homozygous Gpi-1(b)) recipients. The recipients were mated with B6CBF1 males. The birth and size of each litter was recorded. The electrophoretic variant of glucose phosphate isomerase was determined for each neonate. Twelve of 13 recipients of fresh ovary and 10 of 12 recipients of frozen ovary were fertile. Of these, 10 (fresh) and eight (frozen) had litters derived from the ovarian grafts only, or from the graft and native ovary. The breeding characteristics of recipients of fresh and frozen grafts were similar. The reproductive lifespan of the recipients of fresh (6.2 litters) and frozen (8.4 litters) grafts was similar to that of unoperated C57BL/6-Gpi-1(a) control females mated with B6CBF1 males (6.3 litters). Litter size was similar in recipients of grafted ovaries (fresh, 5.4 pups/litter; frozen, 6.3 pups/litter) and C57BL/6-Gpi-1(a) females (6.3 pups/litter). The results suggest that cryopreservation per se does not affect the long-term viability of ovarian tissue and provides an option for storing female germ cells. This is the first unequivocal demonstration that a normal reproductive lifespan can be restored by orthotopic grafting of frozen ovary.     

Growth allometry of organs, muscles and bones in mice from lines divergently selected on the basis of plasma insulin-like growth factor-I.

Growth allometry was examined over the range 6 to 112 days of age in male and female mice from lines selected for low (L) or high (H) plasma concentrations of insulin-like growth factor-I (IGF-I). Plasma IGF-I concentrations were greater in the H line than in L line mice from 28 days of age. H line mice also had greater liveweights and weights of the heart, kidneys, pancreas, lungs, liver, brain and testes from 21-28 days of age. Changes in weights of these organs reflected the general pattern of body growth, there being no consistent effects of selection line on allometric growth coefficients. Ovarian weights were not different between the lines. For muscle weights, (gastrocnemius, quadriceps femoris), the weights or lengths of bones (tibia, femur) and the nose-anus and anus-tail lengths, allometric growth coefficients were generally higher (P less than .05) in L line females than in L line males or H line mice of either sex. The allometric growth coefficient for spleen was significantly (P less than .05) greater in H line mice than in L line mice with the result that spleen weights were 30% higher in H line mice from 28 days of age. This is consistent with results from mice treated with, or transgenic for, IGF-I and suggests a specific effect of this hormone on growth of the spleen. Thymus weights were also greater in H line than in L line mice and developmental patterns of thymus weight closely paralleled those of circulating IGF-I.     

Description and implications for analysis of brain growth in suckling mice

The growth pattern of the brains of normal CD-1 mice was studied from day 1 through day 21 after birth. The main purpose of the study was to decide on suitable methods of statistical analysis of these kinds of data including whether to analyze brain weight or the brain-to-body weight ratio. A secondary purpose, which aided the main purpose, was to find functions that describe the relationships between growth parameters. Linear-linear segmented polynomials were found to describe well the relationships between brain weight and body weight, brain weight and age, brain-to-body weight ratio and body weight and brain-to-body weight ratio and age. The analyses indicated that brain weight alone is the preferred variable to analyze. Regression analysis of brain weight with sex and up to the first three powers of body weight and age as independent variables would be a suitable method of analysis. Litter size per se had no effect on brain weight.     

Skeletal muscle cellularity in mice selected for large body size and in controls.

Body composition and skeletal muscle weights, fiber diameters, fiber numbers, and RNA and DNA concentrations were studied in mice selected for large body size (GLW) compared to an unselected control (C) line. At 60 days of age, body weight of GLW mice was 70 to 75% greater than C mice, but % body water, fat or dry fat-free residue did not differ between the lines. In both GLW and C mice, greater muscle weight in males compared to females was due to larger diameter fibers and not to significant differences in fiber number between sexes, although in most cases, males had slightly higher mean fiber number. Fiber diameters were similar in the two lines and the greater muscle weights of GLW mice were due to more fibers than in the muscles of C mice. RNA and DNA concentrations were slightly, but not significantly, higher in GLW skeletal muscles.     

Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size

Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F₂ intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week—a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F₂ and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.     

Effect of litter size (i.e. nutrition) on carbon monoxide-induced persistent heart changes

It was hypothesized that manipulation of litter size, thus nutrition, which has been shown to alter the neonatal response to cardiovascular stress (i.e. carbon monoxide) might also alter persistent post-stress changes. Rat pups reared in litters of 4 and 16 inhaled 500 ppm CO for 32 days ("CO"), or served as controls ("AIR"). Some pups were killed at 14-15 days of age to assess initial cardiomegaly. As adults, right ventricle (RV) mass was greater in CO/4 males (123 days of age) and females (113 days of age) than in same sex CO/16 rats. Persistent RV cardiomegaly was present in CO/4 males and females compared to AIR's of the same litter size and sex, whereas this was the case only in females comparing CO/16 and AIR/16 rats. RV mass was significantly larger in AIR/4 males than in AIR/16 males. Plots of initial cardiomegaly (both ventricles) versus persistent cardiomegaly (RV) for large and small litters produced similar slopes for the two sexes, with females lying above males. Resting heart rate, monitored in males (66-121 days of age) and females (81-109 days of age), was increased by small litter size, and also by CO, particularly in the males. Resting heart rate was significantly correlated with RV weight. RV DNA content and concentration were increased by small litter size in the males, and concentration also by CO. The male CO/4 rats had the highest DNA content and concentration. In the females, DNA content was increased by small litter size and was greatest in the CO/4 group. Thus, the effects of small litter size have lasting effects: i.e. augmented persistent cardiomegaly, persistent tachycardia, and myocardial DNA content and concentration.     

11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids

11beta-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert 11-keto derivatives. As 11beta-hydroxysteroid dehydrogenase type 2 is highly expressed in the developing brain, but not in the adult CNS, we hypothesized that it may represent a protective barrier to the deleterious actions of corticosteroids on proliferating cells. To test this hypothesis we have investigated the development and growth of the cerebellum in neonatal C57BL/6 mice and mice lacking 11beta-hydroxysteroid dehydrogenase type 2 (-/-). 11beta-Hydroxysteroid dehydrogenase type 2-/- mice had consistently lower body weight throughout the neonatal period, coupled with a smaller brain size although this was normalized when corrected for body weight. The cerebellar size was smaller in 11beta-hydroxysteroid dehydrogenase type 2-/- mice, due to decreases in size of both the molecular and internal granule layers. When exogenous corticosterone was administered to the pups between postnatal days 4 and 13, 11beta-hydroxysteroid dehydrogenase type 2(-/-) mice were more sensitive, showing further inhibition of cerebellar growth while the wildtype mice were not affected. Upon withdrawal of exogenous steroid, there was a rebound growth spurt so that at day 21 postnatally, the cerebellar size in 11beta-hydroxysteroid dehydrogenase type 2-/- mice was similar to untreated mice of the same genotype. Furthermore, 11beta-hydroxysteroid dehydrogenase type 2-/- mice had a delay in the attainment of neurodevelopmental landmarks such as negative geotaxis and eye opening. We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure.     

Effect of pre- and postweaning nutrition on dietary induced obesity in B6D2F2 mice

Our purpose was to ascertain whether a phase of postnatal overfeeding would interact with preweaning litter size in influencing dietary induced obesity in mice. Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters were maintained on high fat (HF) or control diets (C) for 6 weeks, beginning at weaning. After a further 4 weeks on lab chow, all animals were fed a cafeteria diet for another 6 week period. Body weight at weaning indicated Lg less than Md and Sm animals. Lg animals gained more weight during the postweaning period but their body weight remained lower than the Sm. HF animals from all litter sizes consumed more calories and gained more weight than C animals. During the period of cafeteria feeding the Sm animals gained more weight than the Md and Lg. Although males were heavier than females, the sexes responded similarly to treatment. The postweaning dietary regimen had no effect on the weight gained in response to cafeteria feeding.     

Impact of various ecological parameters on the life-history characteristics of Bufotes viridis sitibundus from Turkey

In this study, we used the skeletochronology method to estimate various growth parameters, such as age structure, minimum and maximum life span, age of sexual maturity, and the relationship between body size and weight of eight different populations of the variable toad, Bufotes viridis sitibundus, in Turkey. Further, we determined the relationship between these parameters and ecologic factors using the partial Mantel test. A significant difference was found among the populations with respect to age, body size, and body weight in both males and females. On average, the maximum life span was recorded as 10 years for males and 11 years for females. In the studied populations, the average age of sexual maturity ranged between 2 and 4 years for both sexes. Sexual dimorphism in terms of snout-vent length (SVL) was not observed between males and females in all the populations. Toads from the higher altitudes tended to be significantly larger, older, and heavier than those from lower altitudes. We concluded that altitude and temperature have an impact on the growth rate, body size, and body mass.     

Sex‐Related Shape Dimorphism in the Human Radiocarpal and Midcarpal Joints

Previous research has revealed significant size differences between human male and female carpal bones but it is unknown if there are significant shape differences as well. This study investigated sex‐related shape variation and allometric patterns in five carpal bones that make up the radiocarpal and midcarpal joints in modern humans. We found that many aspects of carpal shape (76% of all variables quantified) were similar between males and females, despite variation in size. However, 10 of the shape ratios were significantly different between males and females, with at least one significant shape difference observed in each carpal bone. Within‐sex standard major axis regressions (SMA) of the numerator (i.e., the linear variables) on the denominator (i.e., the geometric mean) for each significantly different shape ratio indicated that most linear variables scaled with positive allometry in both males and females, and that for eight of the shape ratios, sex‐related shape variation is associated with statistically similar sex‐specific scaling relationships. Only the length of the scaphoid body and the height of the lunate triquetrum facet showed a significantly higher SMA slope in females compared with males. These findings indicate that the significant differences in the majority of the shape ratios are a function of subtle (i.e., not statistically significant) scaling differences between males and females. There are a number of potential developmental, functional, and evolutionary factors that may cause sex‐related shape differences in the human carpus. The results highlight the potential for subtle differences in scaling to result in functionally significant differences in shape. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.