Return to search

Foetal programming for improved immune resistance against gastrointestinal parasites in rats and sheep

Abstract Experiments in this thesis were conducted to investigate the possibility of bestowing lambs with increased resistance to gastrointestinal parasites through maternal protein and copper supplementation. Reproductive outcomes such as birth weight, haematological parameters and faecal egg counts were used as indices of possible foetal programming. This thesis involved 5 experiments. The first three experiments were done using rats as a preliminary study animal on account of their short generational intervals and high fecundity. The final two experiments involved Merino sheep. The first experiment in Chapter 4 investigated the most optimum larval dose to use in order to elicit a measurable immune response. Weaned offspring were infected with a rat nematode, Nippostrongylus brasiliensis and their response measured by faecal egg counts, parasite recovery from intestines at sacrifice, spleen weights and leucocyte numbers, especially manifested as eosinophilia. There was no significant difference in parasite rejection for rats infected with 1000 larvae/rat. When rats were infected with variable larval doses to determine the optimum dose rate, eosinophilia and spleen weight were significantly increased as dose rate increased from 500 L3 to 2,000 larvae. Based on these results, it was decided to use 1,000 larvae for each rat in Chapter 6. The experiment in Chapter 5 involved feeding diets with 5 graded concentrations of copper (Cu) ranging from deficient (1 ppm diet) to high (16 ppm diet). Rats were fed for 4 weeks before mating after which half of them were sacrificed to determine liver Cu concentrations and haematological parameters. The rest were mated and maintained on their respective Cu diets into the second trimester of pregnancy. Pregnant females were sacrificed on approximately gestational Day 10 to recover foetuses and determine the incidence of foetal defects, foetal Cu status as well as maternal liver copper status. It was determined that most morphological defects occurred for the 1 ppm foetuses and both 2 ppm and 4 ppm had similar incidences of brain enlargements. The 16 ppm copper diet was excessive evidenced by reduced liver iron status and erythrocyte counts to similar levels as for 2 ppm rats although it had no adverse effect on foetal development. Significant differences were found for liver Cu status, erythrocyte counts and spleen weights due to the copper diets. A deficient copper diet containing 1 ppm Cu (LC) and an adequate diet containing 8 ppm Cu (SC) were used for the last rat experiment in Chapter 6 which was funded by the Science and Innovation Award. The LC diets were fed for 4 weeks prior to mating. Rats were then fed LC throughout pregnancy, for the 1st trimester only or for the 1st and 2nd trimesters. Other pregnant females were fed the SC diet throughout pregnancy. Offspring were challenged with 1000 L3 N. brasiliensis and their immune responses measured. Copper deficiency at variable stages of prenatal development caused significant postnatal mortalities but had no effect on response to parasite resistance. However, significant parasite and sex effects were found for parameters such as spleen weight, eosinophilia and weight loss during infection. The foetal brain enlargement caused by the deficient 1 ppm Cu diet was determined to be reversible in vivo upon exposure to a normal 8 ppm Cu diet during gestation. Chapter 7 involved Merino ewes which were fed either a high protein diet (21%) or adequate protein diet (12%) during the first 2 trimesters of pregnancy. Production parameters measured included pregnancy weight gain, fleece yield, protein content in milk as well as birth weight of lambs but none were significantly different. After weaning, the lambs were experimentally infected with 10,000 Haemonchus contortus larvae. Barber’s pole worm is responsible for millions of dollars in production losses in the sheep industry. Responses measured were eosinophilia, faecal egg count, anaemia (PCV) and weight gain/loss during the infection period. No significant differences were found for any parameter tested except for a parasite effect on erythrocyte numbers and PCV. In Chapter 8 Merino ewes were used which were mildly Cu deficient due to grazing on pasture that was copper deficient. Control ewes were supplemented with copper oxide wire particles at mating and mid-pregnancy. The rest of the experiment was the same as for Chapter 7 in terms of Barber’s pole worm larval dose. There were no significant differences in birth weight, weaning weight or ewe fleece weights due to copper status. There were no differences in parasite resistance in the lambs due to maternal Cu status measured by live weights, eosinophil concentrations or faecal egg counts. In conclusion, foetal programming by maternal nutritional supplements for postnatal parasite resistance appears to be impossible. It may be that if a different organ was targeted, such as the spleen, the results would have been different. The thymus appears to be non-programmable during foetal development in rats and sheep. However, it was a worthwhile attempt at conferring resistance to parasites in lambs due to the urgency in combating the global problem of parasite resistance to anthelmintics and the resultant large economic losses that are experienced by the global sheep industry.

Identiferoai:union.ndltd.org:ADTP/254149
CreatorsFrancoise Mcpherson
Source SetsAustraliasian Digital Theses Program
Detected LanguageEnglish

Page generated in 0.0022 seconds