Value of Nuchal Translucency in Detection of Chromosomal Aberration in Vietnam Population

Objective: To examine the sensitivity and specificity of different thresholds of nuchal translucency in diagnosis of chromosomal defects. Study Design: This is a longitudinal study of pregnant women have first trimester screening and ultrasound in center of diagnostic antenatal of national hospital of obstetrics and gynecology. A follow-up was made to identify, in all singleton pregnancies in both group of which fetal karyotyping was made and group of normal fetuses. The threshold for nuchal translucency was divided in to above the 95th percentile, the 99th percentile, the 3.0mm and 2.5 MoM of nuchal translucency. The sensitivity and specificity ware calculated in order to diagnosis the chromosomal abbreviation. Results: The research identified 2645 fetuses, 743 amniocentesis (28%). There is 32.4% fetus has NT ≥ the 95th percentile, 28.6% ≥ 2.5mm percentile, 22.3% ≥ 3.0mm, 16.6% above 2.5 MoM. The fetal karyotype was abnormal in 157 (5.8%) pregnancies. The popular conditions were found including trisomy 21(52.2%). Then structural rearrangements occupied 31.2%. Other chromosomes like 13,18,21 occupied 12.7%. The abnormal of sex chromosome was smallest proportion with only 3.8%. At the 95th percentile of nuchal translucency has the highest sensitivity in detection of chromosomal defects (99.4%) but the threshold 2.5mm has a better detection rate (20.4%). The cut off 3.0mm has a better positive prediction rate (22.3%) but could detect less defects (only 132/157 abbreviation). The threshold 2.5xMoM had the highest specificity (86.4%) but lowest sensitivity (only 65%). Conclusion: In fetuses with increased nuchal translucency, more than a half of the chromosomally abnormal group is affected by defects other than trisomy 21 (52.2%). Using threshold 2.5mm helps detect more 23 chromosomal defects in comparison with the threshold 3.0mm and it had the highest average of sensitivity and specificity (87.25%).

CHROMOSOMAL DEFECTS IN INCREASED NUCHAL TRANSLUCENCY FETUS

Objectives: Determination of the prevalence of all chromosomal defects and its distribution in fetuses with increased nuchal translucency thickness. Methodology: This is a retrospective study among pregnant women indicated for amniocentesis by nuchal translucency above 2.5 mm and consent to the study. 2720 cases were included to the study during 6 years’ period from 2015 to 2020. All singleton pregnancies whose nuchal transluciency measurements were equal or over 2.5mm, were indicated for amniocentesis. Results: The study was consist of 2720 amniocentesis in which fetal nuchal transluciency was elevated. The median maternal age was 29.19 years old (range 17-46), and the median fetal crown-rump length was 66.9 mm (range 45– 84). The fetal karyotype was abnormal in 560 (20.6%) pregnancies. The popular chromosomal conditions were including trisomy 21(55%), trisomy 18 (11.2%), trisomy 13 (3.9%), 45, XO (2.7%). Chromosomal aberrations rate was 17.6% at maternal age of 30- 34, 34% and 50.0% at maternal age of 35- 39 and ≥ 40 respectively. Conclusion: In fetuses with increased nuchal translucency, more than a half of the chromosomal aberrations were trisomy 21 (55.0%). Structural rearrangements were 22.5%. Advanced maternal age (above 35) increases the risk of chromosomal aberrations.

Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development

Microtubules that assemble the mitotic spindle are generated by centrosomal nucleation, chromatin-mediated nucleation, and nucleation from the surface of other microtubules mediated by the augmin complex. Impairment of centrosomal nucleation in apical progenitors of the developing mouse brain induces p53-dependent apoptosis and causes non-lethal microcephaly. Whether disruption of non-centrosomal nucleation has similar effects is unclear. Here we show, using mouse embryos, that conditional knockout of the augmin subunit Haus6 in apical progenitors led to spindle defects and mitotic delay. This triggered massive apoptosis and abortion of brain development. Co-deletion of Trp53 rescued cell death, but surviving progenitors failed to organize a pseudostratified epithelium, and brain development still failed. This could be explained by exacerbated mitotic errors and resulting chromosomal defects including increased DNA damage. Thus, in contrast to centrosomes, augmin is crucial for apical progenitor mitosis, and, even in the absence of p53, for progression of brain development.

Women’s experiences of counselling in cases of a screen-positive prenatal screening result

Objective To study women’s apprehensions, understanding and experiences of counselling concerning a screen-positive result in screening for fetal chromosomal defects. Methods A questionnaire study including different steps of the prenatal screening process was carried out in Helsinki University Hospital. Women’s experiences concerning counselling immediately after a screen-positive result and during further examinations in the Fetal Medicine Unit (FMU) were analyzed. Results 143 women filled in the questionnaire. Less than half of the women considered the primary counselling after a screen-positive result to be explicit (43.9%) and sufficient (43.1%). In the FMU, 88.3% and 89.8% of women were satisfied with the explicitness and sufficiency of counselling. Most women (75%) experienced worry before further examinations but less than half (45%) had considered their personal values concerning diagnostic tests. Half (50.5%) of women expected the worry to continue even if diagnostic tests turn out normal. Most (81%) women were aware that diagnostic tests are voluntary and were confident (85.3%) with their decision to participate. Conclusions After a screen-positive result, women have unanswered questions, experience anxiety and confusion. The possibility of an abnormal screening result is not seriously considered beforehand. To enable an informed consent for prenatal screening, improvements in prescreening counselling during the first visits of antenatal care need to be made.

Mitochondria-targeted therapeutics, MitoQ and BGP-15, reverse aging-associated meiotic spindle defects in mouse and human oocytes

STUDY QUESTION Do mitochondria-targeted therapies reverse ageing- and oxidative stress-induced spindle defects in oocytes from mice and humans? SUMMARY ANSWER Exposure to MitoQ or BGP-15 during IVM protected against spindle and chromosomal defects in mouse oocytes exposed to oxidative stress or derived from reproductively aged mice whilst MitoQ promoted nuclear maturation and protected against chromosomal misalignments in human oocytes. WHAT IS KNOWN ALREADY Spindle and chromosomal abnormalities in oocytes are more prevalent with maternal aging, increasing the risk of aneuploidy, miscarriage and genetic disorders such as Down’s syndrome. The origin of compromised oocyte function may be founded in mitochondrial dysfunction and increased reactive oxygen species (ROS). STUDY DESIGN, SIZE, DURATION Oocytes from young and old mice were treated with MitoQ and/or BGP-15 during IVM. To directly induce mitochondrial dysfunction, oocytes were treated with H2O2, and then treated the MitoQ and/or BGP-15. Immature human oocytes were cultured with or without MitoQ. Each experiment was repeated at least three times, and data were analyzed by unpaired-sample t-test or chi-square test. PARTICIPANTS/MATERIALS, SETTING, METHODS Immature germinal vesicle (GV) stage oocytes from 1-, 12- and 18-month-old mice were obtained from preovulatory ovarian follicles. Oocytes were treated with MitoQ and/or BGP-15 during IVM. GV-stage human oocytes were cultured with or without MitoQ. Mitochondrial membrane potential and mitochondrial ROS were measured by live-cell imaging. Meiotic spindle and chromosome alignments were visualized by immunofluorescent labeling of fixed oocytes and the 3-dimensional images were analyzed by Imaris. MAIN RESULTS AND THE ROLE OF CHANCE MitoQ or BGP-15 during IVM protects against spindle and chromosomal defects in oocytes exposed to oxidative stress and in oocytes from aged mice (P < 0.001). In human oocytes, the presence of MitoQ during IVM promoted nuclear maturation and had a similar positive effect in protecting against chromosomal misalignments (P < 0.001). LIMITATIONS, REASONS FOR CAUTION Our study identifies two excellent candidates that may help to improve fertility in older women. However, these potential therapies must be tested for efficacy in clinical IVM systems, and undergo thorough examination of resultant offspring in preclinical models before utilization. WIDER IMPLICATIONS OF THE FINDINGS Our results using in-vitro systems for oocyte maturation in both mouse and human provide proof of principle that mitochondrially targeted molecules such as MitoQ and BGP-15 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S) The project was financially supported by the National Health and Medical Research Council and Australian Research Council, Australia. U.A.-Z. was supported by the Iraqi Higher Education and Scientific Research Ministry PhD scholarship and O.C. was supported by TUBITAK-1059B191601275. M.P.M. consults for MitoQ Inc. and holds patents in mitochondria-targeted therapies. R.L.R. is an inventor on patents relating to the use of BGP-15 to improve gamete quality. TRIAL REGISTRATION NUMBER N/A

Disruption of augmin-mediated microtubule nucleation in neural stem cells causes p53-dependent apoptosis and aborts brain development

SummaryMicrotubules that assemble the mitotic spindle are generated by three different mechanisms: centrosomal nucleation, chromatin-mediated nucleation, and nucleation from the surface of other microtubules mediated by the augmin complex. Impairment of centrosomal nucleation in apical progenitors of the developing mouse brain induces p53-dependent apoptosis and causes non-lethal microcephaly. Whether disruption of non-centrosomal nucleation has similar effects is unclear. Here we show, using mouse embryos, that conditional knockout of the augmin subunit Haus6 in apical progenitors led to spindle defects and mitotic delay. This triggered massive apoptosis and complete abortion of brain development. Co-deletion of p53 rescued cell death, but brain development was still aborted. This could be explained by exacerbated mitotic errors and resulting chromosomal defects including increased DNA damage. Surviving progenitors had lost apico-basal polarity and failed to organize a pseudostratified epithelium. Thus, in contrast to the centrosomal nucleation pathway, augmin is crucial for apical progenitor mitosis, and, even in the absence of p53, for progression of brain development.