ABSTRACT
PROBLEM: The semi-allogeneic fetus is usually tolerated by the maternal immune system. This was proposed to be modulated by CD4+CD25+foxp3+ regulatory T cells (Treg). We aimed to determine the kinetics of Treg during murine gestation and investigate whether changes in Treg levels respond to hormonal variations during pregnancy or generated changes in the local indolamine dioxygenase (IDO) expression. METHOD OF STUDY: We included in our studies the well-known CBA/JxDBA/2J abortion-prone combination using CBA/JxBALB/c as controls. CBA/JxC57/BL6 and BALB/cxC57/BL6 were included as further controls. Animals were killed on days 0, 2, 5, 8, 10, and 12 of pregnancy to measure the levels of Treg, pregnancy-related hormones and IDO expression. RESULTS: A Treg augmentation in normal pregnancy combinations could be observed on day 2 in several organs contrary to the observations made in abortion-prone mice. No differences in hormonal levels could be seen among all groups. IDO was expressed exclusively in placenta starting from day eight, showing no variations among the groups. CONCLUSION: Differences in Treg levels and pregnancy outcome do not correlate with changes in hormonal levels. In addition, as Treg augmentation takes place early and it is observed mainly in the decidual component of the fetal-maternal interface, IDO does not seem to be the pathway underlying Treg protective activity as proposed for humans.
Subject(s)
Abortion, Veterinary/immunology , Pregnancy, Animal/immunology , T-Lymphocytes, Regulatory/immunology , Abortion, Veterinary/enzymology , Animals , Decidua/immunology , Estradiol/biosynthesis , Estradiol/metabolism , Estrone/biosynthesis , Estrone/metabolism , Female , Fetus/immunology , Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred CBA , Pregnancy , Pregnancy, Animal/metabolism , Progesterone/biosynthesis , Progesterone/metabolism , T-Lymphocytes, Regulatory/metabolismABSTRACT
Glycogen Branching Enzyme Deficiency (GBED), a fatal condition recently identified in fetuses and neonatal foals of the Quarter Horse and Paint Horse lineages, is caused by a nonsense mutation in codon 34 of the GBE1 gene, which prevents the synthesis of a functional GBE protein and severely disrupts glycogen metabolism. The aims of this project were to determine the mutant GBE1 allele frequency in random samples from the major relevant horse breeds, as well as the frequency with which GBED is associated with abortion and early neonatal death using the tissue archives from veterinary diagnostic laboratories. The mutant GBE1 allele frequency in registered Quarter Horse, Paint Horse, and Thoroughbred populations was 0.041, 0.036, and 0.000, respectively. Approximately 2.5% of fetal and early neonatal deaths in Quarter Horse-related breeds submitted to 2 different US diagnostic laboratories were homozygous for the mutant GBE1 allele, with the majority of these being abortions. Retrospective histopathology of the homozygotes detected periodic acid Schiff's (PAS)-positive inclusions in the cardiac or skeletal muscle, which is characteristic of GBED, in 8 out of the 9 cases. Pedigree and genotype analyses supported the hypothesis that GBED is inherited as a simple recessive trait from a single founder. The frequency with which GBED is associated with abortion and neonatal mortality in Quarter Horse-related breeds makes the DNA-based test valuable in determining specific diagnoses and designing matings that avoid conception of a GBED foal.
Subject(s)
1,4-alpha-Glucan Branching Enzyme/deficiency , Alleles , Glycogen Storage Disease Type IV/veterinary , Horse Diseases/enzymology , Horse Diseases/genetics , 1,4-alpha-Glucan Branching Enzyme/genetics , Abortion, Veterinary/enzymology , Abortion, Veterinary/genetics , Abortion, Veterinary/pathology , Animals , Animals, Newborn , DNA/chemistry , DNA/genetics , Female , Genotype , Glycogen Storage Disease Type IV/enzymology , Glycogen Storage Disease Type IV/genetics , Glycogen Storage Disease Type IV/pathology , Histocytochemistry/veterinary , Horse Diseases/pathology , Horses , Muscle, Skeletal/pathology , Myocardium/pathology , Pedigree , Polymerase Chain Reaction/veterinary , Pregnancy , Retrospective StudiesABSTRACT
Cystine aminopeptidase (CAP) activity in tissues and in plasma from pregnant cows was measured at various stages of gestation by using the substrate S-benzyl-L-cysteine-4-nitroanilide. The CAP activity was as high or higher in hepatic and renal tissues as in cotyledonary tissue. Plasma CAP activity was low and did not change with length of gestation, nor did it change when placentation was disrupted by infection with Aspergillus fumigatus.
Subject(s)
Aminopeptidases/metabolism , Aspergillosis/veterinary , Cattle Diseases/enzymology , Cattle/metabolism , Cystinyl Aminopeptidase/metabolism , Pregnancy Complications, Infectious/veterinary , Abortion, Veterinary/enzymology , Animals , Aspergillosis/enzymology , Aspergillus fumigatus , Cystinyl Aminopeptidase/blood , Female , Kidney/enzymology , Placenta/enzymology , Pregnancy , Pregnancy Complications, Infectious/enzymologyABSTRACT
The cystine aminopeptidase (CAP) activity was determined in plasma from guinea pigs at various stages of gestation and in pregnant guinea pigs infected with Campylobacter fetus subspecies intestinalis. The CAP activity decreased with length of gestation, which is in contrast to the changes in activity in persons. Infected guinea pigs near the time of abortion can be distinguished from normal guinea pigs on the basis of plasma CAP activity, if the plasma samples are taken 1 to 2 days before abortion. Among pregnant guinea pigs at the same stage of gestation, CAP activity was lower for infected than for normal pregnant animals. This test might be used to indicate probable disruption of placentation and the onset of abortion in the guinea pig.
