A €1 million UCD project studying cows' reproductive health could be reapplied to humans. Dick Ahlstrom reports
Champion dairy cows produce 10,000 litres of milk a year, but at a cost: their fertility frequently declines. Now a research team at University College Dublin is trying to find out why.
Dairy cattle have become noticeably less able to have young as their milk output has increased, says Dr Alex Evans, a lecturer in the university's department of animal science. He and colleague Dr Pat Lonergan have embarked on a detailed "global gene expression profile" to better understand the complex biochemistry associated with fertility.
The two scientists, part of the integrated biology theme within the Conway Institute of Biomolecular and Biomedical Research, received a four-year, €1 million grant from Science Foundation Ireland to research the genetic control of reproduction. "The SFI grant we got looks at the basic cellular events in reproduction," says Evans.
Issues related to bovine fertility have been examined in a piecemeal way before, but emerging technologies and genome studies offer new tools and a new way of pursuing the subject, says Evans. The genome data can be matched with "DNA microarrays", test systems that can search for up to 18,000 genes at a time.
Evans and Lonergan are looking at the very earliest stages associated with fertility and conception, breaking their study down into three key areas.
These include the growth and development of the ovarian follicle, the structure in the ovary that delivers an egg at ovulation; the changes an egg goes through as it awaits fertilisation; and what happens just after fertilisation.
All of this work can be done in vitro, until the dividing embryo has about 100 cells. "We are interested in the first week of life and how the embryo decides to implant or not," says Evans.
Researchers already have a sound idea of what makes a "good" follicle and what is required for a healthy egg, but little is known about the genes that are switched on and the proteins that are expressed during the period from follicle growth through pre- implantation.
"We will look at the gene expression and see which ones are important," says Evans. "We want to know how does the cell survive, what genes help this."
The DNA microarrays will help their work immensely. They are glass slides covered with tiny "dots" of DNA and a fluorescing agent. The dots contain a key identifying DNA string from a bovine gene.
If a biological sample from a fertilised egg or follicle is placed on the microarray, it will fix to the slide wherever there is a DNA match. The fluorescing agent will then "light up" to show that a match has been made.
The researchers can search for thousands of matches at a time, showing them which genes have been switched on at any stage in the ovulation through pre-implantation process. They can then go in with more accurate tests to confirm that a new gene has been switched on and at what stage.
Then the real challenge begins, according to Evans: trying to decide in detail what part the gene plays in the complex biochemistry of reproduction. This is the real goal of the research, he says.
The object is to understand what controls fertility. They know high-output milk cows are less fertile than others, but the cause remains a mystery.
"We really don't know why that is," he says. "If we can learn from this study, we might be able to understand how to improve fertility."
The knowledge would be applicable to cows and, perhaps, to humans. It might be possible to enhance human fertility and increase the chances of success using in vitro fertilisation. And if you know how to enhance fertility, you will also probably have learned how to reduce it. There have been no genuinely new approaches in human contraception for 20 years, he says. This type of study might throw up some fresh ideas.