National Antivisection Society
2004-05 Infertility - In vitro study of human male sperm cells
Funding of Professor Chris Barratt and Dr Ian Brewis continued for their research into the study of human male infertility at Birmingham Women’s Hospital. During previous research funded by the LDF, the Birmingham scientists established a method by which human testicular tissue, obtained from biopsies, can be transported and stored in such a way as to maintain its cellular function. This is an important step towards encouraging researchers to study sperm cell development in humans rather than rodents and primates. One in six couples in the UK is infertile and so there is a significant research effort.
Now that Dr Brewis and colleagues have established the tissue bank of samples, vital research will be undertaken. Much infertility research has focused on investigating ion (potassium and calcium) channels in sperm and also immature germ cells before they develop into sperm. It is believed that these channels are crucial to enable sperm to fertilise the eggs. Preliminary research carried out by Dr Brewis has indicated that human cells have active potassium channels but inactive calcium channels. This is the first time that either of these has been demonstrated in immature human sperm cells and is in marked contrast to the data obtained by other workers in laboratory rodents.
In collaboration with Cambridge scientists, research has been carried out to ascertain the possibility of developing DNA microarray chips of the testicular material. These chips enable all the genes expressing proteins in a tissue to be identified. Early data from the chips is encouraging. This advance would allow all the essential genes expressed in the human testis (approximately 3000) to be examined on just one glass slide (1cm2). These will be the first in-depth genetic studies performed on human testicular tissue.
Another process associated with infertility is apoptosis, or programmed cell death. In fertile men this is a protective mechanism to remove excessive or genetically damaged cells. However, an imbalance in this process may lead to sperm cells maturing in insufficient numbers or with defects. The development of a reliable human culture system would be a major breakthrough in this field. To date all research on apoptosis in sperm cells has been carried out on rodents, with attendant problems of species differences. There are several key differences in the way that humans and rodents produce sperm cells that makes the data acquired by this animal research unreliable. Dr Brewis and colleagues aim to develop a method to culture human seminiferous tubules (which carry semen through the testis). This will enable detailed study of the biochemical mechanisms of apoptosis in human male germ cells.
Dr Brewis states: “We look forward to further demonstrating that human research is the way forward. Already coworkers are taking notice of our work and discussing the limitations of animal work and potential of their work becoming more human-orientated.”
Dr Brewis and Professor Barratt comment: “In the very large field of reproductive medicine there is still an overwhelming obsession with performing research in animals, particularly rodents but also livestock. We believe very strongly that this is totally unjustifiable and unwarranted as there is now good evidence that there are marked differences at the cellular, molecular, tissue and whole organism level between humans and animals. Co-workers, previously stuck in the mud with their animal work, are now taking notice of human research as a result of data we are currently producing. We are pleased to report that these researchers of international recognition are now discussing the limitations of animal work and the benefits of human research and are beginning to initiate human-based projects.”
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