Effects of Alcohol Use on Sperm Chromatin Structure.

INTRODUCTION: The evaluation of the infertile couple is often complex as multiple factors in both the male and female can contribute, including social history. Previous studies have displayed that male ethanol consumption can disturb sperm motility, nuclear maturity, and DNA integrity, likely resulting in infertility. A previous study primarily looking at vitamin D levels and sperm parameters incidentally demonstrated increased high DNA stainability (HDS), which correlates with immaturity of the sperm nucleus, in males who do not use alcohol. The main purpose of this study is to evaluate the effects of male alcohol use on sperm chromatin structure analysis (SCSA), including DNA fragmentation and HDS. METHODS: This study was a retrospective chart review of 210 consecutive couples that presented to a midsize infertility clinic in the Midwest and had a semen analysis and SCSA performed. Data were extracted from the electronic medical record, de-identified, and independently entered into an Excel spreadsheet by two investigators. The spreadsheets were electronically compared, and discrepancies resolved by reference to the EMR primary data. Data extracted included demographics, tobacco use, alcohol use, occupational exposures, semen analysis results, and SCSA results (DNA fragmentation index (DFI) and HDS. Statistical analysis (regression) was performed on this data set to determine significance with a p-level of 0.05, with primary input being level of alcohol use and outcome being the SCSA parameters. RESULTS: 11% of the cohort had heavy alcohol use (greater tyhan 10 drinks/week), 27% moderate (3-10/week), 34% rare (0.5-3/ week), and 28% no alcohol use. 36% of the cohort had HDS greater than 10% (a marker of immaturity of sperm chromatin). Level of alcohol use was not significantly associated with HDS greater than 10% (p=0.55). Average total DFI was 12.99% (greater than 25% is associated with poorer fertility). Total DFI was not significantly associated with the level of alcohol use (p=0.7). Heavy alcohol use was significantly associated with lower sperm density (p=0.042). Increasing age was significantly associated with increasing DFI (p=0.006), increased sperm density (p=0.002) and lower semen volume (p=0.022). Exposure to heat at work was significantly associated with lower semen volume (p=0.042). Tobacco use was associated with lower sperm motility and lower sperm density (p=0.002). CONCLUSIONS: There was not a significant association between the level of alcohol use (heavy, moderate, rare, or none) and the HDS or DFI of sperm. The overall literature remains equivocal with respect to alcohol's effect on sperm chromatin structure. Heavy alcohol use was associated with lower sperm motility. Alcohol may exert a negative effect on semen parameters via disruption of the testosterone hormonal axis, through direct toxicity to Leydig and/or Sertoli cells, and/or through oxidative damage to sperm DNA. The overall effect on fertility and the possibility of transgenerational effects through DNA damage both require further characterization. Increasing age was associated with poorer sperm parameters as expected. Heat exposure was associated with lower semen volume and tobacco use was associated with lower sperm motility and density.

Ischemic Cerebellar Stroke in a Young Patient With Neurofibromatosis Type 2: A Case Report.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a multifaceted disease characterized primarily by benign CNS tumors, especially meningiomas and vestibular schwannomas. There have been several cases of brainstem ischemic stroke in young NF2 patients reported in the literature. To date, there is no unified theory about the connection between NF2 and pediatric stroke. METHODS: We present a case of ischemia in the left cerebellar peduncle of a young patient with NF2, as well as a narrative review of the literature of previous cases. RESULTS: Serial magnetic resonance images (MRIs) displayed an initial area of restricted diffusion in the left cerebellar peduncle with peripheral enhancement which did improve over several months, consistent with maturing infarct. CONCLUSIONS: Our case joins several others with similar presentations and findings. The primary theory for the cause of brainstem ischemia in juvenile NF2 is a microvascular cause due to deficiency of neurofibromin 2, a regulator of endothelial development. Multicenter studies with large NF2 cohorts are needed to better characterize this syndrome.

Effects of alcohol use on sperm chromatin structure, a retrospective analysis.

BACKGROUND: The evaluation of the infertile couple is often complex as multiple factors in both the male and female can contribute, including social history. Previous studies have displayed that male ethanol consumption can disturb sperm motility, nuclear maturity, and deoxyribonucleic acid (DNA) integrity. The main purpose of this study is to evaluate the effects of male alcohol use on sperm chromatin structure analysis (SCSA®). This study was a retrospective chart review of 209 couples that presented to a midsize infertility clinic in the Midwest and had a semen analysis and SCSA® performed. Data extracted from the electronic medical record included demographics, tobacco use, alcohol use, occupational exposures, semen analysis results, and SCSA® results (DNA Fragmentation index (DFI) and High DNA stainability (HDS)). Statistical analysis was performed on this data set to determine significance with a p-level of 0.05, with the primary input being level of alcohol use and primary outcome being the SCSA® parameters. RESULTS: Overall, 11% of the cohort had heavy alcohol use (> 10 drinks/week), 27% moderate (3-10/week), 34% rare (0.5- < 3/week), and 28% none. 36% of the cohort had HDS > 10% (a marker of immature sperm chromatin). Level of alcohol use was not significantly associated with HDS > 10% or DFI. Heavier alcohol use was significantly associated with lower sperm count (p = 0.042). Increasing age was significantly associated with increasing DNA Fragmentation Index (p = 0.006), increased sperm count (p = 0.002), and lower semen volume (p = 0.022). Exposure to heat at work was significantly associated with lower semen volume (p = 0.042). Tobacco use was associated with lower sperm motility (p < 0.0001) and lower sperm count (p = 0.002). CONCLUSIONS: There was not a significant association between the level of alcohol use and the High DNA Stainability or DNA Fragmentation Index of sperm. Increasing age was associated with semen parameters as expected, heat exposure was associated with lower semen volume, and tobacco use was associated with lower sperm motility and density. Further studies could investigate alcohol use and reactive oxidative species in sperm.

RéSUMé: CONTEXTE: L'évaluation du couple infertile est souvent complexe car de multiples facteurs chez l'homme et la femme peuvent y contribuer, y compris l'histoire sociale. Des études antérieures ont montré que la consommation masculine d'éthanol pouvait altérer la mobilité des spermatozoïdes, la maturité nucléaire et l'intégrité de l'acide désoxyribonucléique (ADN). L'objectif principal de cette étude était d'évaluer les effets de la consommation d'alcool chez les hommes sur l'analyse de la structure de la chromatine des spermatozoïdes (SCSA®). Cette étude consistait en un examen rétrospectif des dossiers de 209 couples qui se sont présentés à une clinique d'infertilité de taille moyenne dans le Midwest et ont subi une analyse du sperme et un SCSA®. Les données extraites du dossier médical électronique comprenaient les données démographiques, le tabagisme, la consommation d'alcool, les expositions professionnelles, les résultats de l'analyse du sperme et les résultats du SCSA® (DFI et HDS). L'analyse statistique effectuée sur cet ensemble de données, pour déterminer la signification avec un niveau p de 0,05, a utilisé comme intrant principal le niveau de consommation d'alcool, le critère de jugement principal étant les paramètres du SCSA®. RéSULTATS: Dans l'ensemble, 11% de la cohorte avait une forte consommation d'alcool (> 10 verres / semaine), 27% modérée (3­10/semaine), 34% rare (0,5 à < 3/semaine) et 28% aucune. 36% de la cohorte avait HDS > 10%. Le niveau de consommation d'alcool n'était pas significativement associé à un HDS > 10% ou au DFI. Une consommation d'alcool plus importante était significativement associée à une diminution du nombre de spermatozoïdes (p = 0,042). L'augmentation de l'âge était significativement associée à une augmentation de l'indice de fragmentation de l'ADN (p = 0,006), à une augmentation du nombre de spermatozoïdes (p = 0,002) et à une diminution du volume séminal (p = 0,022). L'exposition à la chaleur au travail était significativement associée à un volume séminal plus faible (p = 0,042). La consommation de tabac était associée à une mobilité plus faible des spermatozoïdes (p < 0,0001) et à une numération plus faible des spermatozoïdes (p = 0,002). CONCLUSIONS: Il n'y avait pas d'association significative entre le niveau de consommation d'alcool et la stabilité élevée de l'ADN ou l'indice de fragmentation de l'ADN des spermatozoïdes. L'augmentation de l'âge était associée aux paramètres du sperme comme attendu, l'exposition à la chaleur à un volume de sperme plus faible, et la consommation de tabac à une mobilité et une numération plus faibles des spermatozoïdes. Des études à venir pourraient explorer les relations entre consommation d'alcool et espèces oxydatives réactives dans le sperme.