John Aitken | |
---|---|
Born | Bath, England | 4 September 1947
Alma mater | |
Known for | Research in human reproductive medicine Impact of oxidative stress and male infertility |
Awards | 2012 NSW Scientist of the Year, 2016 Carl G. Hartman Award, 2021 Clarke Medal |
Scientific career | |
Fields | Researcher, andrologist/reproductive biologist |
Institutions | |
Doctoral advisor | Roger Short |
Robert John Aitken (born 4 September 1947) [1] is a British reproductive biologist, widely known for identifying oxidative stress as a significant contribution to infertility and its actions on human sperm function. He also made substantial contributions to clinical practice translation in male reproductive health, notably the development of new contraceptive vaccine.
He was born in Bath, England but moved to Australia in 1997, where he took Chair of Biological Sciences at the University of Newcastle, [2] then nominated to Pro-Vice-Chancellor of the Faculty of Health and Medicine and Laureate Professor of Biological Sciences at the University of Newcastle since 2013. [3] He is currently Fellow of the Royal Society of Edinburgh, [4] the Australian Academy of Science [5] and the Australian Academy of Health and Medical Sciences, [6] a former president of the International Society of Andrology. [7] Aitken also founded and directed the Priority Research Centre in Reproduction at the University of Newcastle, where he and his colleagues work on a broad spectrum of reproductive issues from conception to parturition.
Aitken has received many honours for his contributions to science throughout his career, including the Carl G. Hartman Award and the 2012 NSW Scientist. Aitken is the most cited author of several biology journals, particularly in the field of Andrology: Reproduction, Molecular Human Reproduction, International Journal of Andrology, Journal of Andrology. [8]
Aitken was born in Bath, [9] in England, on 4 September 1947. [1] Born into a family of real estate agents in Devon, he attended Barnstaple Boys Grammar School, [9] but quit at the age of 16 to follow his parents' footsteps and become an estate agent. [9] After six months of selling houses to the semi-rural residents of Barnstaple, Aitken decided to return to school. [9] He then re-enrolled at his former school to study art, English, and geography, but they were all full, so he had no choice but to study chemistry, botany, and zoology, despite his initial intention to avoid science. [9]
Aitken graduated from the University of London, where he received a Bachelor of Science (Special Honours) in 1967. [3] While at university, he studied zoology, specifically embryology, [10] which made him interested in reproductive biology, prompting him to pursue a Master's degree in Embryology and Mammalian Reproduction from the University College of North Wales in 1969. [3] [2]
He continued his post-graduate studies focusing on wild animal reproduction in Veterinary Clinical Studies at the University of Cambridge under Professor Roger Short's supervision. [2]
In 1971, Aitken's first paper, "Ultrastructural changes in the uterine glands of the Roe deer during delayed implantation” was published in the Journal of Physiology. [11] After 4 years working with Dr Roger Short, Aitken completed his thesis, [12] and received a PhD for research on reproductive study in roe deer from the University of Cambridge in 1973. [3]
After Cambridge, Aitken started a postdoctoral position at the University of Edinburgh's Institute of Animal Genetics, [3] working collaboratively with Anne McLaren, a graduate from the University of Oxford. [2] However, for the first 12 months at Edinburgh, he had not done any outstanding research due to transformations in study models from descriptive on wild animals to mechanistic approaches using the mouse, as well as changes in laboratories. [2] Despite initial difficulties, he became familiar with new study models of in vitro fertilisation and embryo transfer in the second year. [2] In later years, combining these techniques with electrophoretic analysis of proteins, his publication rate rose dramatically [2] and was being cited by other scientists at that time. [13]
In late 1975, Aitken was invited to study problems associated with fertility regulation at the World Health Organisation (WHO)'s Human Reproduction Unit in Geneva. [3] As consulting scientists of WHO, he and Mike Harper [2] conducted several reviews on fertility control strategies, which help prevent or disrupt implantation. [14]
Returning from the WHO informative sessions, he worked as a postdoctoral fellow at the University of Bordeaux for 1 year [3] before continuing his research activities at the University of Edinburgh in September 1977. [3] [2]
Despite a short period at WHO, Aitken had the opportunity to consider all the problems that concern human health, particular infertility issue, during his time here, which prompted him to pursue research in human reproductive biology. [15]
In 1977, Aitken had been appointed to the first Medical Research Council Centre for Reproductive Health at University of Edinburgh, where he and his team focused on the biochemistry of implantation. [2] During his early days at the newly founded centre, he found an advanced technique for examining proteins and carbohydrates more precisely during the pre-ovulatory period to study hormonal control of implantation. [16] Despite early achievements, his team had suspended all research activities due to material shortage from gynaecology wards. [2]
After months of waiting for clinical supplies, Aitken took the lead in Andrology with Roger Short and David Mortimer's encouragement, [2] despite the fact that the discipline was still in its infancy around the 1950s. [17] With this transition in research styles, he could gain direct access without relying on his clinical colleagues' supply, [2] thus solving the need for clinical materials. In 1982, he was promoted to senior scientist at the Medical Research Council; [3] however, it was initially difficult since he and his team were all obscure about how they could influence this field. [2] After few years with renovated laboratory facilities, Aitken started to focus his future study on clinical research into male contraceptives, androgen physiology, and male infertility, especially molecular mechanisms that regulate sperm function. [2] [18]
Aitken remained at the University of Edinburgh for most of the 1980s to 1990s. It was there that he discovered an abnormally free radical attack in failures of fertilisation [19] and later did research on the relationship between reactive oxygen species and their effects on impaired sperm function. [20] He also proposed new techniques in contraception that had helped prevent sexually transmitted diseases and treat male infertility. [21] These contributions laid the foundation for the reproductive studies done in the latter half of the twentieth century and later. [22] [23]
During the time at the University of Edinburgh, Aitken worked with multiple antibodies to analyse their effects on fertilisation and human sperm function. [24] When he gave the administration of A23187 to spermatozoa from normal fertile and oligospermia, he discovered a decline in fertilisation rates at a higher dose, which reduced sperm motility. [25] In attempt to explain the cellular basis of defective sperm function association in a 1987 paper in the Journal of Reproduction and Fertility , he found a sudden burst of production of reactive oxygen species (ROS) associated with the free radical attack in male infertility. [26] The hyperactive production of ROS causes peroxidative damage to the sperm plasma membrane, which is known as oxidative stress, resulting in loss of sperm function. [23]
The discovery was later acknowledged by thousands of scientists as a foundational concept in studying oxygen species associated pathophysiology. [27] Aitken's paper had expanded on the molecular modifications of oxidants in male infertility and resulted in new therapeutic intervention methods to maintain reproductive function. [28] [29]
Besides discovering oxidative stress, Aitken also improved the male contraceptive vaccine in later years. [21] His paper in the European Journal of Pharmacology in 1990 proposed 3 possible targets, including hCG, zona pellucida and sperm surface for contraception development. [30] This research provided the foundation for designing a long-lasting and reversible form of contraceptives, providing an effective method to help prevent sexually transmitted diseases and control the world's growing population. [21] [31]
The University of Cambridge awarded Aitken a Doctor of Science (ScD) in 1998 to recognise his achievements in gamete biology. [32] At the same time, he got a phone call from the University of Newcastle, inviting him to take up the Chair of Biological Sciences. He first declined because he mistook Newcastle for Newcastle upon Tyne, but then agreed after learning that the university is in Australia. [2] It was here that he later took part in several important roles such as Head of School, Director of an ARC Centre of Excellence then Pro-Vice-Chancellor of the Faculty of Health and Medicine at the University of Newcastle. [33]
While serving high positions at the University of Newcastle, Aitken continued his research career on the reproductive studies. He and his colleagues conducted further research on the effects of oxidative stress on the physiological and functional integrity of human sperm. [34] They also researched related oxidative stress problems, such as genetic alterations in male infertility, which culminated in gene mutations, discussing the possible health issues of the next generation from couples using assisted reproductive technology. [35]
He and his colleagues continued to research safe and reliable contraception vaccinations for controlling human fertility. Their study included developing the potential contraceptive potential of ZP3 peptides [36] and other chemical compositions of these contraceptive agents, implying the potential effectiveness of the anti-hCG antibodies. [37]
During his early years in Australia, Aitken attempted to diverge his studies from human reproductive science. [2] He released articles that helped identify diseases in various Australian species, including Tammar Wallaby and Brushtail possum. [38] In addition, he discovered Ehrlichia platys in dogs in Australia, which had not previously been found in Australian animals. [39] However, after few years, he decided to return to andrology and the pursuit of understanding the cell biology of spermatozoa. [2]
According to Google Scholar, this is the period where Aitken's papers were receiving an increasing number of citations. [40] During this time, Aitken and his team carried out some studies to identify different causes affecting male reproductive health. They found that environmental conditions such as smoking, [41] toxins, and mobile radiation [42] contribute to various health issues. These not simply affect male fertility by causing oxidative stress, but they also cause DNA damage, increasing the risk of a man's children developing infertility or cancer. [41]
Along with the studies on DNA integrity, the effect of radiofrequency radiation [42] on fertility, contraceptive [37] and fertility preservation in patients, Aitken has been working on molecular markers of oxidative stress and developing sensitive methods to measure reactive oxygen species generation by cells. Their discovery showed the effectiveness of numerous diagnostic techniques, such as chemiluminescence, spectrophotometry, and flow cytometry, as an indicator of oxidative stress, emphasizing the general significance of mitochondrial dysregulation in impaired sperm activity. [43]
Despite not gaining much success in the animal study, his contribution to developing immunocontraception on animals ranging from horses, sub-mammalian organisms to annelid worms, oysters, and fish enabled the development of a nonsurgical sterilization technique. In 2015, he received a patent for his "Method for reducing the Reproductive Potential of an Animal" while working with Eileen McLaughlin. [44] His invention revolutionized Australian horse breeding industry, which provided a new method of controlling the horse population and increase their value. [45]
In more recent years, Aitken has been focusing on translational research in male contraception and male infertility. Since 2016, he has been working alongside Memphasis to develop "Felix", a device which uses a patented cell separation technology to more gently and effectively separate sperm from semen samples. [46] This project seeks to increase the collection of vital, stable sperm during the crucial early stages of the IVF process. [47]
Aitken's cultural interests go beyond science. [9]
Before deciding to pursue a career as a scientist, music was his greatest passion. [9] He played the guitar most of the time during his time at the University of London and joined the university's folk music club. He loved the music of Frank Sinatra, Nelson Riddle Orchestra and especially Bob Dylan. [9]
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.
Intracytoplasmic sperm injection is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embryos that may be transferred to a maternal uterus. With this method, the acrosome reaction is skipped.
Infertility is the inability of an animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species. It is the normal state of a human child or other young offspring, because they have not undergone puberty, which is the body's start of reproductive capacity.
Acrosin is a digestive enzyme that acts as a protease. In humans, acrosin is encoded by the ACR gene. Acrosin is released from the acrosome of spermatozoa as a consequence of the acrosome reaction. It aids in the penetration of the Zona Pellucida.
Male contraceptives, also known as male birth control, are methods of preventing pregnancy by interrupting the function of sperm. The main forms of male contraception available today are condoms, vasectomy, and withdrawal, which together represented 20% of global contraceptive use in 2019. New forms of male contraception are in clinical and preclinical stages of research and development, but as of 2024, none have reached regulatory approval for widespread use.
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans, it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity. More recently, advance sperm analyses that examine intracellular sperm components are being developed.
Asthenozoospermia is the medical term for reduced sperm motility. Complete asthenozoospermia, that is, 100% immotile spermatozoa in the ejaculate, is reported at a frequency of 1 of 5000 men. Causes of complete asthenozoospermia include metabolic deficiencies, ultrastructural abnormalities of the sperm flagellum and necrozoospermia.
The hamster zona-free ovum test, or hamster egg-penetration test, or sometimes just hamster test, is an in-vitro test used to study physiological profile of spermatozoa. The primary application of the test is to diagnose male infertility caused by sperm unable to penetrate the ova. The test has limited value, due to expense and a high false negative rate.
Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality. Semen quality is a major factor for fertility.
Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently approved for human use.
The Centre for Human Reproductive Science was established in December 2006 to further develop research and innovation in fertility diagnosis and treatment, working in partnership as the academic and research wing of the Birmingham Women's Fertility Centre at Birmingham Women's Hospital and the University of Birmingham Medical School. A particular emphasis in the biomedical research strategy is placing research and discovery in the true physiological context.
Sperm sorting is a means of choosing what type of sperm cell is to fertilize the egg cell. Several conventional techniques of centrifugation or swim-up. Newly applied methods such as flow cytometry expand the possibilities of sperm sorting and new techniques of sperm sorting are being developed.
Ashok Agarwal is the Director of the Andrology Center, and also the Director of Research at the American Center for Reproductive Medicine at Cleveland Clinic, Cleveland, USA. He is Professor at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, USA. Ashok is a Senior Staff in the Cleveland Clinic's Glickman Urological and Kidney Institute. He has published extensive translational research in human infertility and assisted reproduction.
Obesity is defined as an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. This is often described as a body mass index (BMI) over 30. However, BMI does not account for whether the excess weight is fat or muscle, and is not a measure of body composition. For most people, however, BMI is an indication used worldwide to estimate nutritional status. Obesity is usually the result of consuming more calories than the body needs and not expending that energy by doing exercise. There are genetic causes and hormonal disorders that cause people to gain significant amounts of weight but this is rare. People in the obese category are much more likely to suffer from fertility problems than people of normal healthy weight.
Globozoospermia is a rare and severe form of monomorphic teratozoospermia. This means that the spermatozoa show the same abnormality, and over 85% of spermatozoa in sperm have this abnormality. Globozoospermia is responsible for less than 0.1% of male infertility. It is characterised by round-headed spermatozoa without acrosomes, an abnormal nuclear membrane and midpiece defects. Affected males therefore suffer from either reduced fertility or infertility. Studies suggest that globozoospermia can be either total or partial, however it is unclear whether these two forms are variations on the same syndrome, or actually different syndromes.
Antisperm antibodies (ASA) are antibodies produced against sperm antigens.
Eileen Anne McLaughlin is a Scottish molecular biology academic working in Australia. As of 2021 she is a professor at the University of Wollongong.
The male infertility crisis is an increase in male infertility since the mid-1970s. The issue attracted media attention after a 2017 meta-analysis found that sperm counts had declined by 52.4 percent between 1973 and 2011. The decline is particularly prevalent in Western countries such as New Zealand, Australia, Europe, and North America. A 2022 meta-analysis reported that this decline extends to non-Western countries, namely those in Asia, Africa, Central America, and South America. This meta-analysis also suggests that the decline in sperm counts may be accelerating.
Sarah Martins da SilvaFRCOG is a British gynaecologist and researcher specialising in male infertility. Martins da Silva is a Clinical Reader in reproductive medicine at the University of Dundee. She also works as an honorary consultant gynaecologist at Ninewells Hospital in Dundee, specialising in fertility problems and assisted conception. She was named one of the BBC's "100 Women of 2019" for her contribution to fertility science.
Sperm Chromatin Structure Assay (SCSA) is a diagnostic approach that detects sperm abnormality with a large extent of DNA fragmentation. First described by Evenson in 1980, the assay is a flow cytometric test that detects the vulnerability of sperm DNA to acid-induced denaturation DNA in situ. SCSA measures sperm DNA fragmentation attributed to intrinsic and extrinsic factors and reports the degree of fragmentation in terms of DNA Fragmentation Index (DFI). The use of SCSA expands from evaluation of male infertility and subfertility, toxicology studies and evaluation of quality of laboratory semen samples. Notably, SCSA outcompetes other convention sperm DNA fragmentation (sDF) assays such as TUNEL and COMET in terms of efficiency, objectivity, and repeatability.
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