XCI in preimplantation mouse and human embryos: first there is remodelling .

Female eutherians silence one of their X chromosomes to accomplish an equal dose of X-linked gene expression compared with males. The mouse is the most widely used animal model in XCI research and has proven to be of great significance for understanding the complex mechanism of X-linked dosage compensation. Although the basic principles of XCI are similar in mouse and humans, differences exist in the timing of XCI initiation, the genetic elements involved in XCI regulation and the form of XCI in specific tissues. Therefore, the mouse has its limitations as a model to understand early human XCI and analysis of human tissues is required. In this review, we describe these differences with respect to initiation of XCI in human and mouse preimplantation embryos, the extra-embryonic tissues and the in vitro model of the epiblast: the embryonic stem cells.

Defective deacetylation of histone 4 K12 in human oocytes is associated with advanced maternal age and chromosome misalignment.

BACKGROUND: Chromosome segregation errors during human oocyte meiosis are associated with low fertility in humans and the incidence of these errors increases with advancing maternal age. Studies of mitosis and meiosis suggest that defective remodeling of chromatin plays a causative role in aneuploidy. We analyzed the histone deacetylation pattern during the final stages of human oocyte maturation to investigate whether defective epigenetic regulation of chromatin remodeling in human oocytes is related to maternal age and leads to segregation errors. METHODS: Human surplus oocytes of different meiotic maturation stages [germinal vesicle (GV), metaphase (M)I and MII] were collected from standard IVF/ICSI treatments. Oocytes were analyzed for acetylation of different lysines of histone 4 (H4K5, H4K8, H4K12 and H4K16) and for α-tubulin. RESULTS: Human GV oocytes had an intense staining of the chromatin for all four histone 4 lysine acetylations. MI and MII stage oocytes showed either normal deacetylation or various amounts of defective histone deacetylation. Residual H4K12 acetylation was more frequently found in oocytes obtained from older women, with a significant correlation between defective deacetylation and maternal age (r = 0.185, P = 0.007). Eighty-eight percent of the oocytes with residual acetylation had misaligned chromosomes, whereas only 33% of the oocytes that showed correct deacetylated chromatin had misaligned chromosomes (P < 0.001). CONCLUSIONS: We conclude that defective deacetylation during human female meiosis increases with maternal age and is correlated with misaligned chromosomes. As chromosome misalignment predisposes to segregation errors, our data imply that defective regulation of histone deacetylation could be an important factor in age-related aneuploidy.

Parental origin of chromatin in human monopronuclear zygotes revealed by asymmetric histone methylation patterns, differs between IVF and ICSI.

In mouse zygotes, many post-translational histone modifications are asymmetrically present in male and female pronuclei. We investigated whether this principle could be used to determine the genetic composition of monopronuclear human zygotes in conventional IVF and ICSI. First we determined whether male female asymmetry is conserved from mouse to human by staining polypronuclear zygotes with antibodies against a subset of histone N-tail post-translational modifications. To analyze human monopronuclear zygotes, a modification, H3K9me3, was selected that is present in the maternal chromatin. After IVF a total of 45 monopronuclear zygotes were obtained. In 39 (87%) of zygotes a nonuniform staining pattern was observed, proof of a bi-parental origin and assumed to result into a diploid conception. Two zygotes showed no staining for the modification, indicating that the single pronucleus was of paternal origin. Four zygotes contained only maternally derived chromatin. ICSI-derived monopronuclear zygotes (n = 33) could also be divided into three groups based on the staining pattern of their chromatin: (1) of maternal origin (n = 15), (2) of paternal origin (n = 8) or (3) consisting of two chromatin domains as dominating in IVF (n = 10). Our data show that monopronuclear zygotes originating from IVF generally arise through fusion of parental chromatin after sperm penetration. Monopronuclear zygotes derived from ICSI in most cases contain uni-parental chromatin. The fact that chromatin was of paternal origin in 24% of ICSI and in 4% of the IVF zygotes confirms earlier results obtained by FISH on cleavage stages. Our findings are of clinical importance in IVF and ICSI practice.

Dance training intensity at 11-14 years is associated with femoral torsion in classical ballet dancers.

OBJECTIVE: To examine in a cross sectional study the influence of femoral torsion (FT) and passive hip external rotation (PER) on turnout (TO). Starting age, years of classical ballet training, and current and past dance training intensity were assessed to determine their influence on FT, PER, and TO in pre-professional female dancers. METHODS: Sixty four dancers (mean (SD) age 18.16 (1.80) years) were recruited from four different dance training programmes. They completed a dance history questionnaire. FT was measured using a clinical method. PER was measured with the subjects prone, and TO was measured with the subjects standing. RESULTS: Mean TO was 136 degrees, mean unilateral PER was 49.4 degrees, and mean FT was 18.4 degrees. A positive correlation was observed between PER combined (PERC) and TO (r = 0.443, p < 0.001). A negative association was found between FT combined (FTC) and PERC (r = -0.402, p = 0.001). No association was found between starting age or years of classical ballet training and FTC, PERC, or TO. Dancers who trained for six hours a week or more during the 11-14 year age range had less FT than those who trained less (mean difference 6 degrees, 95% confidence interval 1.4 to 10.3). Students currently training for longer had higher levels of TO (p < 0.001) but comparable PERC and FTC. CONCLUSION: FT is significantly associated with PERC. Dancers who trained for six hours a week or more at 11-14 years of age had significantly less FT. FTC had a significant influence on PERC, but no influence on the execution of TO.

Prevalence of overweight and obesity in children and adolescents in a county in Sweden.

UNLABELLED: Overweight among young people in Sweden is increasing. The aim of the present study was to investigate the frequency of overweight and obesity based on body mass index (BMI) values among children and adolescents. Overweight was defined as a BMI value > or = 91st percentile and obesity as a BMI value > 98th percentile on an international reference BMI curve. The study population included boys and girls from four age groups: 9, 12, 15 and 18 y. The data consisted of self-reported measures of height and weight that were obtained from questionnaires used in a cross-sectional study in December 1997. A validation study was performed using a part of the study population. A total of 7011 (81.7%) participants completed the questionnaire. The correlation between self-reported estimations and objective measures of height and weight was high in the oldest age groups (0.88-0.98), but lower in the 9-y-old age groups (0.37-0.72). These self-reported estimations in the 9-y-olds were excluded from further analysis. It was found that 12.3%, 11.6% and 11.4% of the boys in the 12-, 15- and 18-y-old age groups and 6.8%, 5.5% and 4.8% of the girls in the same age groups were overweight and 7.9%, 8.9% and 7.3% of the boys and 5.1%, 4.2% and 3.9% of the girls were obese. CONCLUSION: The prevalence of overweight and obesity was found to be high in the study population and is a serious public health problem. The prevalence of obesity was significantly higher (p < 0.05) in 15-y-old boys living in rural areas than in city and town dwellers of the same age.

Nedocromil sodium 2% eye drops for twice-daily treatment of seasonal allergic conjunctivitis: a Swedish multicentre placebo-controlled study in children allergic to birch pollen.

This was a multicentre, double-blind, randomized group comparative study in which 77 children, aged 6-16 years, received 2% nedocromil sodium eye drops and 72 received placebo, one drop into each eye twice daily. The treatment period was 4 weeks, covering the peak birch pollen season. Prior to the start of the season, patients who had attended the clinic the previous 2 years because of seasonal allergic conjunctivitis (SAC) to birch pollen, entered a one week baseline period during which symptoms were assessed, dairy cards completed, and routine sampling of blood and urine carried out. The double-blind treatment period then commenced at the onset of the birch pollen season. Patients/parents kept daily diary record cards of eye symptom severity and concomitant therapy. Conjunctivitis was mild in both treatment groups but nedocromil sodium was more effective than placebo in controlling symptoms. During the 2-3 weeks of peak pollen counts, this therapeutic effect was statistically significant for itching (P < 0.01), watering (P < 0.05) and total symptom score (P < 0.01), but was not significant for grittiness (P = 0.08) or redness (P = 0.06). Global opinions of efficacy showed no difference between treatments, due to a high placebo effect (however, the diary card data indicated a significant improvement with nedocromil sodium). We therefore conclude that nedocromil sodium 2% eye drops, administered twice daily, is an effective treatment for SAC in children.

Salbutamol in the treatment of asthmatic children. A comparison of oral and inhalation therapy alone and in combination.

In 10 children with asthma and reversible bronchial obstruction the effect on lung function (VC, FVC and FEV1) of salbutamol was tested comparing oral administration, inhalation or a combination of both. The oral treatment was carried out as a randomized double-blind salbutamol-placebo cross-over study followed by inhalation of salbutamol in all patients. In agreement with previous findings in adults, the study showed a significant increase of FEV1, FVC and VC (P less than 0.005) after oral salbutamol. Combined oral and inhalation medication of salbutamol gave a significantly higher increase of FEV1, VC (P less than 0.01) and FVC (P less than 0.05) when compared with oral therapy only. Compared with salbutamol inhalation only, the combined therapy gave a significantly higher FEV1 (P less than 0.01). The relatively high oral dose used produced no side effects.