Writers of romantic songs may tell us that women are complicated beings, but if you want to hear how complicated women are, try talking to a reproductive endocrinologist.
Associate Professor John Evans has spent the past three decades looking at the female reproductive system, from the early stirrings of ovulation through to determining the mechanics of maintaining a successful pregnancy. Now his work in the Department of Obstetrics and Gynaecology at Otago’s Christchurch School of Medicine and Health Sciences has seen him gather a multi-disciplinary research team which has combined the biological, mathematical and engineering sciences in an attempt to gain an understanding of what is happening at a fundamental level.
At the heart of the work are the inter-relationships between the complicated series of biochemical actions and responses within the pituitary gland and ovaries which governs when and how an egg is released. Understand the pathways involved and the functioning of the various chemicals using them, and you can get a handle on basic processes that can be used to control fertilisation.
This information is as important to those looking for different forms of contraception as it is to those wanting to boost the success rates of infertility treatments. Both groups need to identify and, ideally, understand what is happening in a woman’s body during ovulation in order to be able to gain some control over that process.
“You can talk about the ovulatory cycle for a long time. It’s pretty complicated and very interesting,” Evans enthuses. “Change is characteristic of the ovulatory cycle.”
Two major hormones are under scrutiny – luteinising hormone (LH) and GnRH – the first produced by the pituitary gland and the second in the hypothalamus. The ovulation process is mediated by a complex cocktail of these and other substances, such as the peptide oxytocin, the levels of which rise and fall in relationship to each other throughout the ovulatory cycle. GnRH, for example, is released in a series of pulses which serve to prime and then boost the amount of LH released. Such information has important implications in areas such as fertility treatment. Initial research in this area in the 70s assumed that when trying to boost ovulation and fertility, the more GnRH in the system, the better. Evans says that the discovery of the pulsed release of GnRH and its timing have shown them to be important factors too, which need to be understood when trying to mediate the process.
While much of this work has involved human volunteers, engineering principles are now being applied to this biochemical problem, in a collaboration funded by the MacDiarmid Institute.
“MacDiarmid could see some advantages in having some biological input, and we could see advantages in having an engineer involved in what we do,” Evans notes.
The atomic force microscope (AFM) at the University of Canterbury is being used to provide a very narrow probe which allows interactions with a specimen at the atomic level. Dr Maan Alkaisi is guiding this early application of the new field of nanotechnology, which involves working at the extreme edge of the atomic world where forces between atoms and individual particles loom large.
Victoria University’s Dr Kate McGrath is part of the group, and a number of PhD students and research assistants, drawn from the disciplines of engineering and biochemistry, are involved in various aspects of these investigations. It’s a collaboration which has produced some promising early results. Evans is finding the work exciting, as the AFM allows him to look directly at a living cell and how it responds to changes in its environment. Conventional microscopy, such as that permitted by electron microscopes, Usually requires cells to be treated – flash-frozen, coated in gold foil, held in a vacuum – in order to be viewed, destroying any chance of examining a cell in its natural state.
With the developing AFM system, cells from the pituitary gland can be held in individual cavities on a platform and flooded with a variety of chemicals to mimic changes in the body. Tiny pores on the cells cluster within pits where biological processes take place, and these can be scanned by the AFM during the process of exocytosis when hormones such as LH are released through the cell surface.
Electrical fields can be used to shepherd cells into the cavities, separating them out via the differing charges on the cell surface. This permits identification of different functional groupings of cells, which can then be more closely examined for their varying responses to materials added to the mix.
“With this [technology] we can do all sorts of interesting things to these groups of cells.”
Ultimately Evans is hoping that the work, which also involves French researchers, will lead to a “lab on a chip” concept that will make it easier to undertake exacting research programmes in this intensely complicated area.
The platform and AFM provides the researchers with a chance to look at what an individual cell is doing and then go back an hour or two later to reexamine it. While Evans is looking at the cells themselves, mathematicians from the University of Canterbury are looking to develop abstract models that describe the relationships between all the various important aspects of the system, release relationships and feedback and inhibition processes.
“Then we can get an idea of the relative input of the various factors at different times.”
The complex rise and fall of the various substances through the cycle is more than simply a fascinating technical issue however. Evans is well aware that what he’s doing is important in the real world.
“The subject has a lot of international interest and the work here is being noticed.”
If this work does make it easier for women to control their fertility, whether aiming to conceive or not, then such attention is certain to grow.
Above: A tiny cell sits in a cavity produced by nanofabrication techniques at Canterbury University as part of a collaborative project between researchers in engineering and the biological sciences. Image courtesy of Dr Maan Alkaisi, University of Canterbury.