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Abstract The impact of Bariatric Surgery (BS) on maternal and neonatal outcomes among pregnant women is not fully understood, especially in comparison to different weight categories. The primary aim of this study is to assess the factors associated to women who have undergone BS. The study also investigates the maternal and neonatal outcomes amongst this group in comparison to the three Body Mass Index (BMI) groups (women with obesity, overweight and normal weight). A 12-month population-based retrospective study was conducted using registry data from the PEARL-Peristat Study at the Women's Wellness and Research Center (WWRC) in Qatar from January 1, 2017, through December 31, 2017. Both univariate and multivariable regression analyses were employed to scrutinize risk factors and maternal and neonatal outcomes. The study included 6212 parturient women, of which 315 had a history of BS, while 5897 with no BS history. Qatari women, aged 35 and higher, with parity > 1, diabetes, and hypertension were more likely to be in the post-BS group. Women in the post-BS group were found to be more likely to have a cesarean delivery (37.5% vs. 24%, Adjusted Odds Ratio (aOR) = 1.59, CI 1.18–2.14), preterm babies (10% vs. 7%, aOR = 1.66, CI 1.06–2.59), and stillbirth (1.6% vs. 0.4%, aOR = 4.53, CI 1.33–15.50) compared to the normal weight women group. Moreover, post-BS women had a higher risk of low-birth-weight neonates than women with obesity (15% vs. 8%, aOR = 1.77, CI 1.153–2.73), overweight (15% vs. 7%, aOR = 1.63, CI 1.09–2.43), and normal weight (15% vs. 8%, aOR = 1.838, CI 1.23–2.75). Finally, women in the post-BS group were more likely to have low-birth-weight neonates amongst term babies than women with obesity and overweight. Pregnancies with post-BS should be considered a high-risk group for certain medical outcomes and should be monitored closely. These findings may guide the future clinical decisions of antenatal and postnatal follow-up for post-BS women.

Abstract Rhabdomyosarcoma 2-associated transcript (RMST) long non-coding RNA has previously been shown to cause Kallmann syndrome (KS), a rare genetic disorder characterized by congenital hypogonadotropic hypogonadism (CHH) and olfactory dysfunction. In the present study, we generated large deletions of approximately 41.55 kb in the RMST gene in human pluripotent stem cells using CRISPR/Cas9 gene editing. To evaluate the impact of RMST deletion, these cells were differentiated into hypothalamic neurons that include 10–15% neurons that express gonadotrophin-releasing hormone (GnRH). We found that deletion in RMST did not impair the neurogenesis of GnRH neurons, however, the hypothalamic neurons were electro-physiologically hyperactive and had increased calcium influx activity compared to control. Transcriptomic and epigenetic analyses showed that RMST deletion caused altered expression of key genes involved in neuronal development, ion channels, synaptic signaling and cell adhesion. The in vitro generation of these RMST-deleted GnRH neurons provides an excellent cell-based model to dissect the molecular mechanism of RMST function in Kallmann syndrome and its role in hypothalamic neuronal development.

The human ribosomal DNA (rDNA) copy number (CN) has been challenging to analyse, and its sequence has been excluded from reference genomes due to its highly repetitive nature. The 45S rDNA locus encodes essential components of the cell, nevertheless rDNA displays high inter-individual CN variation that could influence human health and disease. CN alterations in rDNA have been hypothesized as a possible factor in autism spectrum disorders (ASD) and were shown to be altered in Schizophrenia patients. We tested whether whole-genome bisulphite sequencing can be used to simultaneously quantify rDNA CN and measure DNA methylation at the 45S rDNA locus. Using this approach, we observed high inter-individual variation in rDNA CN, and limited intra-individual copy differences in several post-mortem tissues. Furthermore, we did not observe any significant alterations in rDNA CN or DNA methylation in Autism Spectrum Disorder (ASD) brains in 16 ASD vs 11 control samples. Similarly, no difference was detected when comparing neurons form 28 Schizophrenia (Scz) patients vs 25 controls or oligodendrocytes from 22 Scz samples vs 20 controls. However, our analysis revealed a strong positive correlation between CN and DNA methylation at the 45S rDNA locus in multiple tissues. This was observed in brain and confirmed in small intestine, adipose tissue, and gastric tissue. This should shed light on a possible dosage compensation mechanism that silences additional rDNA copies to ensure homoeostatic regulation of ribosome biogenesis.