Student Seminar
Faheem Seedat and Sally Galal
Tuesday, 07 May 2024, 1pm to 2pm
Hosted by seminars@wrh.ox.ac.uk
Faheem Seedat (13:00 - 13:30)
Title: Unravelling the influence of placental signalling molecules on pancreatic islet cell alterations during pregnancy
Abstract: Insulin secretion increases progressively during pregnancy to maintain normal maternal blood glucose levels. The placenta secretes hormones and extracellular vesicles (EVs) into maternal circulation that signal peripheral tissues. It is these placental-derived signalling molecules that drive changes in pregnancy physiology. We have investigated the impact of placental signalling molecules on pancreatic islets through a multifaceted approach. We have examined the role of extracellular vesicles (EVs) utilising a human beta cell model. Additionally, we have analysed pancreatic histology samples obtained from pregnant women by immunohistochemistry complemented with downstream computational quantification and proteomics approaches to explore the effects of placental derived hormones. This comprehensive approach has allowed us to gain a deeper understanding of how placental-derived signalling molecules influence pregnancy islet physiology in humans. While previous studies in rodent models have suggested that hormones and EVs from the placenta can modulate insulin secretion in pancreatic β islet cells, our research aims to determine the translational relevance of these findings to human biology.
Sally Galal (13:30 - 14:00)
Title: The clinical diagnosis and treatment of phospholipase C zeta (PLCζ) deficiency and the development of a nanoparticle-mediated delivery method for sperm
Abstract: Infertility represents a significant challenge in reproductive medicine and can arise from male, female or unexplained factors. The prevalence of male infertility has increased over the last few decades, predominantly due to deficiencies in sperm function. Assisted reproductive technology (ART) represents a powerful tool with which to treat such cases, particularly the application of intracytoplasmic sperm injection (ICSI). However, ICSI failure can occur in some cases, a condition that is known as oocyte activation deficiency (OAD). Under normal circumstances, oocyte activation (OA) is initiated by a sperm factor known as phospholipase C zeta (PLCζ) which induces the release of intracellular calcium (Ca2+) within the fertilized oocyte in a series of characteristic oscillations. Previously, our group showed that reduced levels of PLCζ expression, low proportions of sperm expressing PLCζ, and PLCζ mutation can all lead to OAD. Thus, PLCζ represents a significant diagnostic and therapeutic target. Our group has also generated a recombinant form of PLCζ that could be used as a potential therapeutic for OAD. However, several challenges remain; we know little about the manner in which the PLCζ gene is expressed and translated, or the regulatory mechanisms involved. Furthermore, there are clear challenges associated with the stability and delivery of the PLCζ protein. In this talk, I will present my DPhil research, including the validation of a clinical PLCζ assay that we provide for The Fertility Partnership (Oxford), mechanistic investigations of PLCζ expression, and the development of a novel solid silica nanoparticle (SSNP)-mediated system for delivering biological tools to mammalian sperm as a research or clinical tool