What happens during early fetal development has a profound impact on health that lasts a lifetime. It is clear that if we wish to genuinely impact on rates of disease and disability in the population at large, we must invest in research to better understand and treat the events that impact development in the womb.
We are undertaking research to look at the events that occur during conception and early pregnancy to improve pregnancy rates for women who struggle to conceive and improve health outcomes for babies in general.
Improving IVF by better nurturing the embryo in the first 5 days
There is great potential to improve IVF success: Approximately 22% of IVF cycles result in a live birth. This rate is the same globally, but lower for women aged over 38, because their embryos are more likely to be genetically abnormal (as a result of genetic mutations). However, Genesis research has shown that the biggest reason IVF fails is abnormal development of the embryo. Genetic abnormality contributes to this, but so does the composition of the artificial fluid which cultures the embryo. This “medium” contains the nutrients to produce proteins and energy, which allow the embryo to develop. A new research project beginning in Autumn 2021 aims to improve balance of constituents for the medium in which the embryo develops for five days. Even though the IVF process involves selecting the best embryos for implantation, microscopic analysis of embryos cannot identify how well cells are functioning, because metabolic process are at a molecular level. Improved techniques for analysing the chemical composition of a sample (sensitive mass spectroscopy) now open up new possibilities for this research: Analysis of the media before and after the period of embryo culture reveals the amount of various chemicals that the embryo has used and produced. This comparison sheds light on the embryo’s metabolic processes. These careful measurements are the first of their kind. Analysis from a preliminary study has proven information, and also suggests a link between an embryo’s high metabolism and chance of success – for implantation, healthy pregnancy and birth.
Understanding the Genetic Cause of Male Infertility
Men who don’t produce sperm lack a certain gene, which usually appears multiple times in a particular section of the Y chromosome. Even the absence of one instance of this gene causes problems with sperm production, but we don’t know why. We know how the gene initially acts on messenger RNA in terms of its reaction with protein, but we don’t know the further chain of events that impacts sperm production. Andrew Childs’ project aims to discover its effect by comparing what happens in germ cells with and without the gene. This will help us understand how male infertility can have a genetic cause – and be inherited through assisted reproductive techniques.
The role of Hormones and Receptors in Endometrial cancer
Endometrial cancer (EC) is the most common gynaecological malignancy and rising globally. But we have little understanding of the underlying mechanisms.
EC usually occurs during the postmenopausal period where there are elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones have a vital role in reproduction, which involves activating serpentine receptors (left); a type of protein “woven” into the surface of cells. We have previously funded research that links these receptors to EC. A new project aims to identify a way we might be able to develop drugs to target these receptors. Research completed in February 2022 confirmed that FSH also causes an increase in the size of lipid droplets, which may provide energy for cancer cells and resistance to treatment.