Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene.
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The expression of uncoupling protein (UCP)-3 mRNA in skeletal muscle is dramatically reduced during lactation in mice. The reduction in UCP-3 mRNA levels lowers the amount of the UCP-3 protein in skeletal muscle mitochondria during lactation. Spontaneous or abrupt weaning reverses the downregulation of the UCP-3 mRNA but not the reduction in UCP-3 protein levels. In lactating and virgin mice, however, fasting increases UCP-3 mRNA levels. Changes in UCP-3 mRNA occur in parallel with modifications in the levels of free fatty acids, which are reduced in lactation and are upregulated due to weaning or fasting. Modifications in the energy nutritional stress of lactating dams achieved by manipulating litter sizes do not influence UCP-3 mRNA levels in skeletal muscle. Conversely, when mice are fed a high-fat diet after parturition, the downregulation of UCP-3 mRNA and UCP-3 protein levels due to lactation is partially reversed, as is the reduction in serum free fatty acid levels. Treatment of lactating mice with a single injection of bezafibrate, an activator of the peroxisome proliferator-activated receptor (PPAR), raises UCP-3 mRNA in skeletal muscle to levels similar to those in virgin mice. 4-chloro-6-[(2,3-xylidine)-pirimidinylthio] acetic acid (WY-14,643), a specific ligand of the PPAR-alpha subtype, causes the most dramatic increase in UCP-3 mRNA, whereas troglitazone, a specific activator of PPAR-gamma, also significantly increases UCP-3 mRNA abundance in skeletal muscle of lactating mice. However, in virgin mice, bezafibrate and WY-14,643 do not significantly affect UCP-3 mRNA expression, whereas troglitazone is at least as effective as it is in lactating dams. It is proposed that the UCP-3 gene is regulated in skeletal muscle during lactation in response to changes in circulating free fatty acids by mechanisms involving activation of PPARs. The impaired expression of the UCP-3 gene is consistent with the involvement of UCP-3 gene regulation in the reduction of the use of fatty acids as fuel by the skeletal muscle and in impaired adaptative thermogenesis, both of which are major metabolic adaptations that occur during lactation. (+info)
Genetic analysis of litter size in Targhee, Suffolk, and Polypay sheep.
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Data on litter size, weaning weights at 60, 90, and 120 d, postweaning gains from weaning to 120 or 365 d of age, fleece weight, and fiber diameter from Targhee, Suffolk, and Polypay flocks participating in the U.S. National Sheep Improvement Program were used to estimate genetic parameters for litter size and genetic relationships between early-life traits and future litter size. Records on 7,591 lambings by 3,131 Targhee ewes, 10,295 lambings by 5,038 Suffolk ewes, and 6,061 lambings by 2,709 Polypay ewes were used. Heritability estimates for litter size ranged from .09 to .11 across breeds; repeatability ranged from .09 to .13. Additive genetic effects on litter size were generally positively, and occasionally significantly, correlated with animal additive genetic effects on weaning weights and postweaning gains. Genetic correlations (r(a)) ranged from .08 to .48 in Targhee and from .17 to .43 in Suffolk but were close to 0 in Polypay (-.14 to .09). Additive maternal effects on weaning weight were positively associated with litter size in Suffolk and Polypay; this correlation was negative (-.23 to -.35), but not significant, in Targhee. Fleece weight was not strongly associated with litter size; (r(a) = -.09 to .21). However, fiber diameter had a significant undesirable correlation with litter size (.30) in Targhee. Estimates of phenotypic correlations of litter size with early-life traits were uniformly small (-.02 to .08). Thus, although occasional genetic antagonisms between litter size and early-life traits were observed in these data, none appeared large enough to prevent simultaneous genetic improvement in both traits. (+info)
Histoincompatibility and maternal immunological status as determinants of fetoplacental weight and litter size in rodents.
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Studies conducted upon inbred strains of mice, hamsters and rats have shown that following the interstrain matings the now familiar covert reactivity of pregnant females to the alloantigens of their conceptuses may benefit the latter in two ways; firstly, it exerts a significant influence upon placental weight, and indirectly upon the birth weight of the fetus-allogeneic placentas tending to be heavier than syngeneic placentas, and mothers specifically presensitized against alien paternal tissue antigens gestate fetuses with heavier placentas than normal females. Specifically tolerant mothers, on the other hand, produce smaller, F1 hybrid, fetoplacental (fp) units. The classic notion that the disparity between the birth weights of F1 hybrid and homozygous offspring is due to hybrid vigor has been challenged by the finding that DA and (DA times F1)F1 hybrid blastocysts transferred to the uteri of genetically tolerant (DA times F1)F1 hybrid rats produce fp units of similar weight Maternal immunological reactivity against the fetus qua allograft may make a significant contribution here. Additional support for the premise that maternal reactivity against fetal alloantigens in some way promotes the growth of the fp unit was afforded by the finding that excision of the para-aortic lymph nodes (which drain the uterine horns) from females before interstrain matings resulted in smaller fp units than in females subjected to sham operations. The finding with one rat strain combination that passive immunization of females with serum against their F1 hybrid conceptuses promoted the growth of the latter suggests that a humoral rather than a cellular immunity may be involved. Secondly, in the three species studied, it was observed that genetic disparity between a conceptus and its mother significantly improved its chances of implantation and development to term. (+info)
Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension.
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Epidemiological studies have indicated that susceptibility of human adults to hypertension and cardiovascular disease may result from intrauterine growth restriction and low birth weight induced by maternal undernutrition. Although the 'foetal origins of adult disease' hypothesis has significant relevance to preventative healthcare, the origin and biological mechanisms of foetal programming are largely unknown. Here, we investigate the origin, embryonic phenotype and potential maternal mechanisms of programming within an established rat model. Maternal low protein diet (LPD) fed during only the preimplantation period of development (0-4.25 days after mating), before return to control diet for the remainder of gestation, induced programming of altered birthweight, postnatal growth rate, hypertension and organ/body-weight ratios in either male or female offspring at up to 12 weeks of age. Preimplantation embryos collected from dams after 0-4.25 days of maternal LPD displayed significantly reduced cell numbers, first within the inner cell mass (ICM; early blastocyst), and later within both ICM and trophectoderm lineages (mid/late blastocyst), apparently induced by a slower rate of cellular proliferation rather than by increased apoptosis. The LPD regimen significantly reduced insulin and essential amino acid levels, and increased glucose levels within maternal serum by day 4 of development. Our data indicate that long-term programming of postnatal growth and physiology can be induced irreversibly during the preimplantation period of development by maternal protein undernutrition. Further, we propose that the mildly hyperglycaemic and amino acid-depleted maternal environment generated by undernutrition may act as an early mechanism of programming and initiate conditions of 'metabolic stress', restricting early embryonic proliferation and the generation of appropriately sized stem-cell lineages. (+info)
Bayesian analysis of response to selection: a case study using litter size in Danish Yorkshire pigs.
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Implementation of a Bayesian analysis of a selection experiment is illustrated using litter size [total number of piglets born (TNB)] in Danish Yorkshire pigs. Other traits studied include average litter weight at birth (WTAB) and proportion of piglets born dead (PRBD). Response to selection for TNB was analyzed with a number of models, which differed in their level of hierarchy, in their prior distributions, and in the parametric form of the likelihoods. A model assessment study favored a particular form of an additive genetic model. With this model, the Monte Carlo estimate of the 95% probability interval of response to selection was (0.23; 0.60), with a posterior mean of 0.43 piglets. WTAB showed a correlated response of -7.2 g, with a 95% probability interval equal to (-33.1; 18.9). The posterior mean of the genetic correlation between TNB and WTAB was -0.23 with a 95% probability interval equal to (-0.46; -0.01). PRBD was studied informally; it increases with larger litters, when litter size is >7 piglets born. A number of methodological issues related to the Bayesian model assessment study are discussed, as well as the genetic consequences of inferring response to selection using additive genetic models. (+info)
Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation.
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Mice with a targeted mutation of the Hoxa10 gene demonstrate uterine factor infertility. It is unclear if the defect in the uterine environment arises due to the absence of Hoxa10 expression during embryonic development or in the adult. We have recently demonstrated that HOXA10 expression in human endometrium rises dramatically at the time of implantation, suggesting maternal expression of Hoxa10/HOXA10 may be essential to the process. To assess the importance of maternal Hoxa 10 expression, the uteri of day 2 pregnant mice were injected with a DNA/liposome complex containing constructs designed to alter maternal Hoxa10 expression before implantation. Transfection with a Hoxa10 antisense oligodeoxyribonucleotide significantly decreased the number of implantation sites. Transfection with a plasmid which constitutively expresses Hoxa10 optimized survival of implanted embryos resulting in increased litter size. These results demonstrate that maternal Hoxa10 expression is essential for implantation and is the first report of the maternal alteration of a gene known to affect implantation specifically. We also demonstrate that DNA/liposome complexes containing the same Hoxa10 constructs that alter fertility in mice, can affect Hoxa10 expression in a human endometrial cell line. Alteration of human endometrial HOXA10 via liposome-mediated gene transfection is a potential contraceptive agent or fertility treatment. (+info)
Role of mother-young interactions in the survival of offspring in domestic mammals.
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The defining characteristic of mammals is that females nurse and care for their young; without this, the neonate has no chance to survive. Studies on wild and domestic species show that the neonatal period is the most critical step in the lifetime of a mammal. This review compares three well-studied species (the rabbit, pig and sheep) that differ in their parental strategies and in the problems that neonates have to overcome. As a general trend, mother-young interactions vary according to the maturity of the newborn, and the size of the litter. Neonatal survival relies to a great extent on an environment that is ecologically appropriate for the developmental stage of the neonate, and on optimum interactions with the mother. Adaptive maternal care supposes that the mother provides the basic needs of the neonate: warmth (in pigs and rabbits) or shelter, food, water and immunological protection (via colostrum) and, in some instances, protection from predators and other conspecifics. A major risk facing all neonates, other than the birth process itself, is inadequate colostrum intake owing to delayed suckling or competition with siblings, which leads to starvation, hypothermia or even crushing, as has been observed in pigs. (+info)
Effect of brood size manipulation on offspring physiology: an experiment with passerine birds.
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The environment experienced during ontogeny has a significant impact on the physiological condition of offspring. This, in turn, forecasts survival probabilities and future reproductive potential. Despite the prominent role that the concept of condition plays in evolutionary studies, the physiological and biochemical characters that define it remain relatively unexplored. In this study, we quantified the impact of brood size manipulations on the physiology and biochemistry of nestling tree swallows (Tachycineta bicolor) shortly before they fledged. Over two breeding seasons, we either increased or decreased the number of individuals in a brood by a single nestling. Every 2-4 days, we determined the resting rate of oxygen consumption [V(O(2))] of individuals in each brood. Growth was followed until 16 days of age, at which time, to look for potential trade-offs in energy allocation, we measured total lipid mass, skeletal muscle and organ mass, indices of blood oxygen-carrying capacity and the activities of key metabolic enzymes in various tissues. Surprisingly, there was a minimal response of most characters to brood manipulation, suggesting that physiological and biochemical development is relatively invariant except perhaps under extreme conditions. Individuals reared in artificially enlarged broods, however, had a significantly lower body mass, body-size-adjusted [V(O(2))], gizzard mass and total lipid mass. These individuals also had decreased activity of cardiac 3-hydroxyacyl CoA dehydrogenase, suggesting a decreased capacity for oxidation of fatty acids. How these characters affect survival or the future adult phenotype remains unknown. (+info)