The expression and distribution of deoxyribonucleic acid repair and apoptosis markers in testicular germ cells of infertile varicocele patients resembles that of old fertile men.

OBJECTIVE: To explore the expression and distribution of DNA damage repair and apoptosis marker proteins in human testicular germ cells of infertile varicocele patients; and to compare the expression and distribution with that of young and old fertile men. DESIGN: Retrospective case-control study. SETTING: Academic institutions. PATIENT(S): Testicular specimens were obtained from 8 infertile varicocele patients aged 20-30 years and from 16 fertile volunteers aged 20-82 years. INTERVENTION(S): Testicular germ cell DNA repair markers were assessed using immunohistochemical staining for the cell proliferation marker (proliferating cell nuclear antigen), DNA repair markers [poly(ADP-ribose) polymerase-1 (PARP-1), poly(ADP-ribose), X-ray repair cross-complementing 1, and apurinic/apyrimidinic endonuclease 1], and apoptosis markers (caspase 9, active caspase 3, and cleaved PARP-1). MAIN OUTCOME MEASURE(S): The prevalence and cellular localization of the above markers in testicular tissues of varicocele patients and fertile men of varying ages. RESULT(S): Statistically significant differences in DNA damage repair-associated proteins and apoptosis markers were observed in infertile men with varicocele compared with fertile young men. Old fertile men showed similar expression of the same markers when compared with infertile varicocele patients. CONCLUSION(S): The study demonstrates that there is an increase in human testicular germ cell DNA repair and apoptosis in infertile varicocele patients and that their profile resembles that of premature aging.

Deoxyribonucleic acid repair and apoptosis in testicular germ cells of aging fertile men: the role of the poly(adenosine diphosphate-ribosyl)ation pathway.

OBJECTIVE: To explore the relationship between men's age and DNA damage repair proteins related to apoptosis in human testicular germ cells. DESIGN: Retrospective case-control study. SETTING: Academic institutions. PATIENT(S): Testicular specimens were obtained from 22 fertile volunteers aged 20-82 years. INTERVENTION(S): Deoxyribonucleic acid repair markers were assessed using immunohistochemical staining for the cell proliferation marker [proliferating cell nuclear antigen (PCNA)]; DNA repair markers [poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1), poly(adenosine diphosphate-ribose) (PAR), X-ray repair cross-complementing1(XRCC1), and apurinic/apyrimidinic endonuclease 1 (APE1)]; and apoptosis-associated markers (caspase 9, active caspase 3, and cleaved PARP-1). MAIN OUTCOME MEASURE(S): The prevalence and cellular localization of the above markers in testicular tissues of young, middle aged, and old men. RESULT(S): Statistically significant differences in DNA damage repair-associated proteins (PARP-1, PAR, XRCC1, and APE1), and apoptosis markers (caspase 9, active caspase 3, and cleaved PARP-1) were observed in testicular samples from older men. These differences were most marked in spermatocytes. CONCLUSION(S): The study demonstrates that there is an age-related increase in human testicular germ cell DNA break repair and apoptosis with age.

Effect of laser resurfacing on p53 expression in photoaged facial skin.

BACKGROUND: p53 overexpression has been reported in photoaged skin. Meanwhile, p53 gene mutations have been implicated as an important factor in the pathogenesis of ultraviolet (UV) light-induced skin cancer. OBJECTIVE: The objective was to evaluate the effect of laser resurfacing on the epidermal thickness and expression of p53 in photoaged skin. METHODS: Specimens were obtained from the facial skin of 10 patients before and after 3 months and 1 year of treatment using CO(2) (five cases) and erbium (Er):YAG (five cases) lasers. Specimens were also obtained from six age-matched controls. These biopsies were used for routine histopathology, histometry, and p53 immunoperoxidase staining. RESULTS: Both CO(2) and Er:YAG lasers were found to induce a significant decrease in p53 expression in biopsies obtained after 3 months (p=.0004 and .002, respectively) followed by gradual increase (p=.01 in both groups). A significant increase (p<.01) in epidermal thickness was also observed after 1 year of resurfacing. This increase, however, is inversely correlated with the level of p53 expression in such patients. CONCLUSION: The decrease in epidermal p53 expression after CO(2) and Er:YAG lasers may account for some of the benefits of resurfacing on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.

Effect of topical tretinoin on photoaged facial skin: a histometric, immunohistochemical and ultrastructural study.

BACKGROUND: Topical tretinoin is a recognized treatment for photoageing. AIM: To evaluate the microscopic changes induced by topical tretinoin used to treat mild to moderate photodamage in dark-skinned patients aged 30 to 50 years. PATIENTS AND METHODS: Biopsy specimens were obtained from the facial skin of 11 patients before and after treatment with topical tretinoin. Routine histopathology coupled with histometric computer-assisted image analysis was used to assess epidermal changes. Alcian blue stain was used to measure changes in glycosaminoglycans (GAGs). Immunoperoxidase technique for type I and III collagens and elastin, as well as transmission electron microscopy, were used to measure changes in collagen and elastic fibres. RESULTS: Epidermal hyperplasia occurs following tretinoin application, which is reversible with continued therapy. GAGs decreased (p < 0.05) after 6 months of tretinoin application but with no significant change thereafter. Quantitatively, there was an insignificant decrease of type I (p = 0.7) and III (p = 0.3) collagens during the first 6 months of tretinoin usage. However, biopsies taken after 10 months revealed a statistically significant increase in collagen I from a mean of 75.2% +/- 9.6 before treatment to 94.2% +/- 4.1 after treatment (p = 0.05). Similarly, the amount of type III collagen increased from a mean of 74.6% +/- 9.96 to 90.6% +/- 2.1 after 10 months of treatment (p = 0.05). On the other hand, the amount of elastin significantly (p = 0.02) decreased from a mean of 54.5% +/- 3.68 before treatment to 43.4% +/- 4.42 after 6 months of tretinoin application but with no significant change thereafter. Such changes were associated ultrastructurally with new collagen deposition and improvement of the quality of elastic fibres. CONCLUSION: Topical tretinoin benefits facial skin, mainly by increasing collagen I and III and also by improving the morphological appearance of collagen and elastic fibres.

Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression in facial skin.

The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA damage. It is involved in the decision whether the cells should stop replication and proceed to repair their DNA, or to die by apoptosis. In the present study, we evaluate the effect of some treatment modalities on the expression of p53 in facial skin. Biopsy specimens were obtained from the facial skin of 20 patients before and after treatment using topical tretinoin (11 cases), TCA chemical peeling (5 cases) and dermabrasion (4 cases). Biopsy specimens were also obtained from 12 control subjects representing the same age groups of the patients. Topical tretinoin therapy was found to induce a significant decrease in the expression of p53 up to 6 months of therapy followed by a significant increase after 10 months of therapy. On the contrary, superficial TCA peeling did not induce any statistically significant change in the expression of p53. On the other hand dermabrasion was found to induce a significant decrease in the level of expression of p53 in biopsies obtained after complete re-epithelialization followed by a significant increase. These changes in the expression of p53 may play a role in mediating the effects of such treatment modalities on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.