Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility

Planning for the Pandemic

Over the past year, many of us have become involved in the development of strategic plans for the hospitals, health authorities and clinical practices in which we work in case an influenza pandemic occurs in the very near future. Planning for this on the front lines is difficult, due in large part to the uncertainties involved. How will the pandemic evolve? Is the current H5N1 strain of bird flu going to be 'the' one? How closely will the pandemic resemble that of 1918? Will it have the same transmission characteristics as the yearly endemic influenza strains or will it be so different that our routine infection prevention precautions for influenza will be ineffective? Will there be a useful vaccine that is widely available and safe? That the current death rate associated with H5N1 strain infections in humans is approximately 60% is quite frightening; an influenza pandemic with such a high death rate is almost incomprehensible. Therefore, it is a relief to hear that the upper estimates are at a much lower rate of approximately 5% in most suggested epidemiological models. Will the use of oseltamivir really work to prevent infection, illness, morbidity or death? If so, will there be sufficient supplies available in Canada? How are we supposed to make plans so that our medical system, which is already quite stressed, will be functional under the extreme conditions that are anticipated? One major difficulty is that we do not actually know how soon, if at all, the pandemic will occur. Specific, highly detailed plans made today may not be applicable in the future. As a result, most contingency plans are being made for a generic situation based on the general assumption that some percentage of the workforce will be absent from work for some specified period of time. In general, the plans tend to be impersonal because they concentrate on essential functions that need to be undertaken in an institution and assume that, with training, all personnel can cross-cover these services to accommodate for those times when the employees who routinely perform those tasks are absent

It's time for a national immunization strategy

Canada needs to develop and implement a national immunization strategy to provide optimal protection for vaccine-preventable diseases for children, adolescents and adults. Although the federal government has a mandate to ensure that access to health care is equitable across the country, it is the mandate of provincial governments to actually provide health care services. Thus, while the federal government makes recommendations for the optimal use of various vaccines through the publications of the National Advisory Committee on Immunization, the provincial governments must develop and fund their individual immunization programs. With a national immunization strategy that is endorsed by the federal and provincial governments, the following could occur: harmonization of childhood immunization schedules across the country; efficient introduction of new vaccines; the ability to enhance the monitoring of vaccine use and adverse events; and improvements in the ability to access readily vaccine products in the most cost effective manner. A national immunization strategy would also provide opportunities for vaccine and immunization research, and for improved education of health care providers and the general public

Reflections

Ideally, editorials are written one to two months before publication in the Journal. It was my turn to write this one. I had planned to write the first draft the evening after my clinic on Tuesday, September 11. It didn't get done that night or during the next week. Somehow, the topic that I had originally chosen just didn't seem that important anymore as I, along my friends and colleagues, reflected on the changes that the events of that day were likely to have on our lives