The role of genetic variability of the host on the resistance to Neospora caninum infection in cattle.

Neospora caninum is one of the most frequently diagnosed abortifacient pathogens in cattle. There is abundant genomic information about the parasite itself, but very little is known about the genetic variability of resistance in the most common intermediate host. The aim of this review was to compile all the available information about the genetic variability associated with the resistance to N. caninum both between and within cattle breeds. We systematically searched for published studies that investigated the influence of genetics of the host on the prevalence of N. caninum and risk of abortion. Beyond the potential confounding effects of feeding systems, management and animal density, some lines of evidence suggest that Holstein, the most popular breed for milk production, has a comparatively higher risk of abortion due to infections by N. caninum, whereas some beef breeds from Continental Europe seem to be more resistant. It is still not clear if different genetic mechanisms of resistance are involved in the two known routes of infection: postnatal ingestion of oocysts or transplacental transmission from the infected dam to the fetus. Genomic information associated with susceptibility to infection and risk of abortion in different cattle breeds is still scarce. The information reported here could be useful to identify new research alternatives and to define novel strategies to deal with this major problem of animal production.

Impact of mouse pregnancy on thymic T lymphocyte subsets.

It has been reported that fetal lymphoid progenitor cells are acquired during gestation and are able to develop in the maternal mouse thymus into functional T cells. Moreover, previous pregnancies increase the number of fetal cells in the mother. In the present study, we investigated whether mouse pregnancy induces changes in T lymphocyte subsets in the maternal thymus. We determined the T lymphocyte subsets in two allogeneic cross-breedings, namely CBA/J×BALB/c (normal) and CBA/J×DBA/2 (abortion prone), and investigated the effects of the age and parity of the female, as well as pregnancy outcome, on thymocyte populations. In addition, hormonal effects were evaluated in a syngeneic combination (CBA/J×CBA/J). We found that during pregnancy both hormonal and allogeneic stimuli induced a reduction in the CD4(+)CD8(+) subset with an increase in the CD4(+)CD8(-) population. Only young females of the normal combination exhibited an increase in the CD4(-)CD8(+) population. All young mice showed an increase in CD4(+)CD25(+)FoxP3(+) T cells. Interestingly, the γδT thymus pool was increased in all females of the normal allogeneic pregnancy only, suggesting the participation of this pool in the observed beneficial effect of multiparity in this cross-breeding. Our results demonstrate that allogeneic pregnancies induce important variations in maternal thymocyte subpopulations depending on the age of the female and the male component of the cross-breeding.

Association between single nucleotide polymorphisms in p53 and abortion in Thoroughbred mares.

Single nucleotide polymorphisms (SNPs) in the p53 gene have been studied extensively in humans. The aims of this study were to determine the frequency of the Arg/Pro SNP in p53 in Thoroughbred mares on one stud in Brazil and to correlate p53 genotypes with reproductive performance. SNPs were detected by PCR-restriction fragment length polymorphism in blood samples from 105 horses and confirmed by sequencing. The allele frequency in Thoroughbred mares at codon 72 in exon 4 was 73.3% Arg/Pro, 17.1% Arg/Arg and 9.6% Pro/Pro. The presence of Arg/Pro was significantly associated with abortion (P=0.02), while Pro/Pro mares had a lower probability of abortion (P<0.05). Using a logistic regression model, the dominance effect was significant (P=0.044; odds ratio 7.94) for abortion and additive effects were not significant (P=0.26). p53 may play a role in equine reproduction.

NRAMP1 3' untranslated region polymorphisms are not associated with natural resistance to Brucella abortus in cattle.

The NRAMP1 gene encodes a divalent cation transporter, located in the phagolysosomal membrane of macrophages, that has been associated with resistance to intracellular pathogens. In cattle, natural resistance against brucellosis has been associated with polymorphisms at the 3' untranslated region (3'UTR) of the NRAMP1 gene, which are detectable by single-strand conformational analysis (SSCA). This study aimed to evaluate the association between NRAMP1 3'UTR polymorphisms and resistance against bovine brucellosis in experimental and natural infections. In experimentally infected pregnant cows, abortion occurred in 42.1% of cows with a resistant genotype (SSCA(r); n = 19) and in 43.1% of those with a susceptible genotype (SSCA(s); n = 23). Furthermore, no association between intensity of pathological changes and genotype was detected. In a farm with a very high prevalence of bovine brucellosis, the percentages of strains of the SSCA(r) genotype were 86 and 84% in serologically positive (n = 64) and negative (n = 36) cows, respectively. Therefore, no association was found between the NRAMP1-resistant allele and the resistant phenotype in either experimental or naturally occurring brucellosis. To further support these results, bacterial intracellular survival was assessed in bovine monocyte-derived macrophages from cattle with either the resistant or susceptible genotype. In agreement with our previous results, no difference was observed in the rates of intracellular survival of B. abortus within macrophages from cattle with susceptible or resistant genotypes. Taken together, these results indicate that these polymorphisms at the NRAMP1 3'UTR do not affect resistance against B. abortus in cattle and that they are therefore not suitable markers of natural resistance against bovine brucellosis.

Ovulation rate, litter size and prenatal losses in hair sheep of the French West Indies.

Ovulation rate (OR) and litter size (LS) were recorded in local hair sheep of Martinique and in local x Lacaune-viande crossbreeds, in order to assess prenatal losses. Local hair sheep LS and OR were 1.91 and 2.41, respectively. Prenatal losses increased with OR, from 0.22 (OR = 2) up to 1.50 (OR > 3). The ewes (69.7%) with LS = 1 had actually lost at least one ovum, against 25.9% of the ewes with LS > 1. Ewes grazing Cynodon nlemfuensis (Stargrass) had lower LS than those grazing Digitaria decumbens (Pangola), in relation with a lower nutritional level and, maybe, more parasitism effects. No seasonal or age at lambing effect was shown. The OR and LS were dramatically decreased on local x Lacaune-viande crossbred ewes (minus 1.32 and 0.67 unit, respectively, P < 0.05). This suggests a possible negative effect of the tropical environment on the crossbreeds' reproductive function.

Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface.

CBA/JXDBA/2J murine abortion is known to be associated with increased local and peripheral Th1-cytokines levels. The role of the pro-inflammatory interleukin-6 (IL-6) in murine abortion remains unclear. In humans, IL-6 was reported to be elevated at the onset of spontaneous abortion. The aim of our study was to evaluate the levels of IL-6 during murine pregnancy in (1) the normal murine pregnancy combination CBA/JXBALB/c and in (2) the CBA/JXDBA/2J abortion prone mating combination. We measured IL-6 serum levels by ELISA and local (placental and decidual) IL-6 levels by flow cytometry and immunohistochemistry. The expression of the IL-6 receptor gp80 was further analyzed. We additionally evaluated the number of mast cells and macrophages at the feto-maternal interface as a putative IL-6 source in reproductive tissues. IL-6 and gp80 were expressed in decidual cells as well as in different trophoblast types. Flow cytometry analysis showed increased numbers of IL-6+ cells in abortion placentas and deciduas compared to control pregnant mice. We observed an elevated number of mast cells and macrophages at the feto-maternal interface from abortion mice in comparison to control mice. Interestingly, we found very high numbers of mast cells, macrophages and IL-6+ cells in resorption tissue compared to control tissues. Flow cytometry studies confirmed that macrophages are being an important source of IL-6 at the feto-maternal interface. The mRNA IL-6 levels were also enhanced in placenta and decidua from mice with high abortion rate compared to normal pregnant mice, as analyzed by RT-PCR. Our results suggest that IL-6 produced not only by immunocompetent cells such as macrophages and mast cells, but also by trophoblasts and decidua cells, is directly involved in the pathology of abortion.