Robert GILCHRIST (Australia)
A/Professor Robert Gilchrist is a NHMRC Senior Research Fellow and Director of Research at the School of Women’s and Children’s Health, at the University of New South Wales Sydney. He is an oocyte biologist conducting both discovery and applied research. He investigates oocyte-somatic cell interactions as a determinant of subsequent embryonic development. He recently identified cumulin, a heterodimer of GDF9 and BMP15, and showed that it regulates oocyte quality. Dr Gilchrist also studies new biomarkers of oocyte quality. He has published >100 peer-reviewed papers including 20 reviews/chapters. He currently has an H-index of 43 with >6,000 citations.
Simulated Physiological Oocyte Maturation (SPOM) and Related IVM System
Oocyte in vitro maturation (IVM) makes use of oocytes from patients and animals that have received minimal gonadotrophin stimulation. Whilst this brings many advantages to patients, this typically means oocytes are collected from small – medium sized (4- 12 mm) antral follicles, and these oocytes are still in the process of acquiring the capacity to support subsequent embryo development. Furthermore, removal of such oocytes from the follicle and culture in vitro leads to spontaneous oocyte meiotic maturation, without the benefit of the physiological signals that naturally induce oocyte maturation at ovulation. Over the past decade seminal advances have been made in our understanding of the fundamental mechanisms regulating oocyte maturation in vivo. In particular, we have learned that natriuretic peptides and cGMP are responsible for cAMP-mediated meiotic arrest and that the ovulatory gonadotrophin surge reverses these processes. Also ovulation causes a transient surge in follicular somatic cell cAMP and this is important for subsequent oocyte developmental competence. This is significant as IVM systems, as practised clinically, typically do not recapitulate this cAMP surge in vitro, possibly accounting for the lower efficiency of IVM compared to clinical IVF (1). A broader objective of my research program is to restore in vitro, as far as possible, the natural processes that occur during oocyte maturation in vivo. One means to achieve this in IVM is to: 1) prevent spontaneous meiotic resumption at oocyte collection using phosphodiesterase inhibitors, then 2) artificially elevate cumulus-oocyte complex (COC) cAMP levels using agents such as forskolin or dbcAMP, and finally to 3) induce meiotic resumption using FSH or EGF-like peptides. One such induced-oocyte maturation system is called simulated physiological oocyte maturation (SPOM) (2). A recent advance on this type of approach is the use of c-type natriuretic peptide as the oocyte meiotic inhibitor (3). Such induced-IVM systems typically lead to subsequent improvements of embryo yield. Translating these findings into improvements in human reproductive medicine is a major challenge. By partnering with research intensive IVF clinics we have been able to use this knowledge to gradually improve human IVM outcomes. This research has implications for improving the efficacy and clinical uptake of clinical IVM and fertility preservation.
1. Gilchrist RB, Luciano AM, Richani D, Zeng HT, Wang X, Vos MD, Sugimura S, Smitz J, Richard FJ, Thompson JG. Oocyte maturation and quality: role of cyclic nucleotides. Reproduction. 2016;152(5):R143-157.
2. Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod. 2010;25(12):2999-3011.
3. Sanchez F, Lolicato F, Romero S, De Vos M, Van Ranst H, Verheyen G, Anckaert E, Smitz JEJ. An improved IVM method for cumulus-oocyte complexes from small follicles in polycystic ovary syndrome patients enhances oocyte competence and embryo yield. Hum Reprod. 2017;32(10):2056-2068.