Immunobiology of fertility in mares
This research project aims to provide insights into disrupted mechanisms accounting for currently unidentified pregnancy losses and either lead to a means of prevention, or at least provide explanations for why a mare may terminate a pregnancy that is not viable.
This would lead to an improved ability to monitor embryo implantation, and will enable equine veterinarians to provide improved health management, regardless of the outcome.
The overarching goal of our research program is to improve fertility and reproductive health in mares through a better understanding of reproductive events such as conception and early pregnancy. Ultimately we aim to reduce the occurrence of early pregnancy failure. To address this issue, we focus on understanding the cellular and molecular mechanisms that regulate a number of key processes:
- early conceptus development and function, in particular development of the specialised cells of the placenta
- modulation of the immune response in early pregnancy
- regulation of hormone production and
- changes in the uterus in pregnancy.
The research performed under this Home Office project licence has used horses to explore aspects of early equine placental development primarily for the benefit of improving the fertility of horses and reducing the need for veterinary intervention or reducing the period of intervention. Mares are kept as a herd and we perform reproductive procedures that are very similar to those performed in routine veterinary stud practice.
Chorionic gonadotropin is a hormone produced by the placenta of both horses and humans during pregnancy, but not by most other species used experimentally. This means that results gained from studies in the horse may also be valuable beyond equine health to provide new knowledge relevant and applicable to human reproduction. Thus potential beneficiaries of this research extend across both veterinary and human spheres, with social impact from advances in both healthcare and animal welfare.
One of the aims of this project is to understand the mechanisms that regulate the differentiation of cells that produce the hormone eCG and ultimately eCG production. Thus a shorter term impact arising from the work will be the enabling of the in vitro production of equine Chorionic Gonadotropin, as a commercial product to induce superovulation in farmed and domestic animals. Currently commercial sources of eCG are produced by purifying the hormone from the serum of farmed pregnant mares, a procedure that can be associated with stress at the time of blood collection and terminating the pregnancy. An in vitro method of production of the hormone would represent initially a form of reduction and ultimately replacement of mares farmed to produce eCG . In 2014, we identified, for the first time, growth factors that induce differentiation of cells that produce eCG. We are now looking at how we can apply this knowledge to an in vitro method of eCG production.
In the longer term, a greater understanding of placental development, immunity in pregnancy and endometrial function will contribute to management of early pregnancy losses. At present 10-20% of early pregnancies are lost. Currently, only approximately 20% of such losses are accounted for by the identification of pathologies (eg infection or developmental abnormalities).