Seeds of concern

Aitken, R. John; Koopman, Peter; Lewis, Sheena

doi:10.1038/432048a

Cited by 320 publications

(213 citation statements)

References 28 publications

(20 reference statements)

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…Although the aetiology of these diseases has traditionally been laid at the door of replication error, this hypothesis does not account for all of the facts, particularly in the case of achondroplasia [27,28]. As an alternative explanation, we have suggested that such mutations arise as a consequence of the aberrant repair of sperm DNA by the oocyte between the moment of fertilization and S phase of the first mitotic division [16,29]. In these circumstances, DNA damage in spermatozoa can be seen as a form of pro-mutation that inadvertently becomes converted into a mutation by the egg in a flawed attempt at DNA repair.…”

Section: The Futurementioning

confidence: 99%

Whither must spermatozoa wander? The future of laboratory seminology

Aitken

2010

Asian J Androl

View full text Add to dashboard Cite

This commentary celebrates the publication of the 5th edition of the World Health Organization Laboratory Manual for the Examination and Processing of Human Semen. This is the most complete text to date on the creation of a conventional semen profile and includes invaluable reference limits for specific aspects of semen quality based on the analysis of over 1 900 recent fathers. The new edition of the manual also includes detailed protocols for monitoring different aspects of sperm function and new chapters on the preparation of spermatozoa for assisted conception and cryopreservation. Given that this publication is the definitive statement on how to perform a descriptive semen analysis, we might speculate on the future of this field and the sorts of tests that might feature in future editions of the manual. Cell biologists are currently being empowered by the 'omics revolution, which is placing at their disposal technologies of unprecedented power to examine the biochemical composition of cells such as spermatozoa. Indeed, spermatozoa are perfect vehicles for this kind of analysis because they can be obtained as extremely pure suspensions, exist naturally in isolation and can be induced to express their capacity for fertilization and the initiation of embryonic development in vitro. The application of 'omics technologies to these cells, in concert with detailed assessments of their functional competence, should provide insights into the biochemical basis of defective semen quality. This information will then help us understand the causes of male infertility and to develop rational methods for its treatment and possible prevention. Keywords: assisted conception, DNA damage, male infertility, miscarriage, semen, seminology, spermatozoa 1 In the beginning A long long time ago, when in vitro fertilization (IVF) was in its first flush of youth and Intracytoplasmic sperm injection (ICSI) had not driven seminology into the reproductive wilderness, the development of robust methods for the diagnosis and treatment of male infertility was regarded as a noble cause worthy of engagement.In those far-off days, the descriptive semen profile was the only means we had of determining the fertility of men attending infertility clinics. This profile focused on an analysis of sperm number, motility and morphology underpinned by the fundamental belief that fertility is essentially a war of attrition. According to this model, the ejaculate must contain more than a certain critical number of motile, morphologically normal spermatozoa in order to withstand the cellular carnage that inevitably accompanies the perilous transition from the point of insemination to the site of fertilization. In diagnostic terms, the concept that male fertility is essentially 'a numbers game' resulted in a preoccupation with threshold counts for sperm number, motility and morphology that define the conventional semen profile, even to this day. The belief that fertility is entirely dependent on sperm number was, ironically,

show abstract

Section: The Futurementioning

confidence: 99%

Whither must spermatozoa wander? The future of laboratory seminology

Aitken

2010

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…Male subfertility is commonly associated with high rates of DNA damage in the spermatozoa, and such damage has, in turn, been correlated with a wide range of adverse clinical outcomes including impaired fertility, disordered embryonic development, high rates of miscarriage and an increased risk of defects in the offspring. [8][9][10] As a result of these linkages, there is an inevitable risk that the use of DNAdamaged spermatozoa in ART will compromise the health of the progeny. We already know that the incidence of birth defects following assisted conception is double that seen in the naturally conceived population 11 and that imprinting disorders, notably the BeckwithWiedemann and Angelman syndromes, seem to be increased in such children.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and DNA damage in human spermatozoa

Aitken¹,

Koppers²

2010

Asian J Androl

281

179

View full text Add to dashboard Cite

DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apoptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

show abstract

“…8 These mutations are thought to arise spontaneously in the germ line of the fathers or are created by aberrant repair of DNA-damaged spermatozoa in the oocyte, for reasons that are still unresolved. 9,10 In addition to Y-chromosome deletions, genetic factors are also involved in other types of male infertility including congenital hypogonadotrophic hypogonadism and congenital absence of the vas deferens. Overall, such major genetic lesions are thought to account for around 15% of male infertility.…”

Section: Importance Of the Demographic Transitionmentioning

confidence: 99%

Falling sperm counts twenty years on: where are we now?

Aitken¹

2013

Asian J Androl

View full text Add to dashboard Cite

Seeds of concern

Cited by 320 publications

References 28 publications

Whither must spermatozoa wander? The future of laboratory seminology

Whither must spermatozoa wander? The future of laboratory seminology

Apoptosis and DNA damage in human spermatozoa

Falling sperm counts twenty years on: where are we now?

Contact Info

Product

Resources

About