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Journal of Indian Association of... 2024Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS...
BACKGROUND AND AIMS
Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS is dependent on the prenatal maternal metabolic environment, the objective of this pilot study was to explore the role of specific maternal plasma metabolites in the etiology of HSCR.
METHODS
In this cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples were obtained from mothers of children diagnosed with HSCR ( = 7) and age-matched mothers of normal children ( = 6). The plasma metabolome was analyzed by ultra-high-pressure liquid chromatography and mass spectrometry. Metabolites were identified by mzCloud using Compound Discoverer software. Using an untargeted metabolomics workflow, metabolites with case versus control group differences were identified.
RESULTS
A total of 268 unique plasma metabolites were identified and annotated in maternal plasma. Of these, 57 were significantly different between case and control groups ( < 0.05, -test). Using a false discovery rate corrected cutoff of 10% to adjust for multiple comparisons, 19 metabolites were significantly different in HSCR cases, including carnitines, medium-chain fatty acids, and glutamic acid. Pathways affected were for amino acid and lipid metabolism.
CONCLUSION
Disordered prenatal metabolic pathways may be involved in the etiopathogenesis of HSCR in the developing fetus. This is the first study to assess maternal plasma metabolomics in HSCR.
PubMed: 38405248
DOI: 10.4103/jiaps.jiaps_134_23 -
IScience Aug 2023Embryo development after fertilization is largely determined by the oocyte quality, which is in turn dependent on the competence of both the cytoplasm and nucleus. Here,...
Embryo development after fertilization is largely determined by the oocyte quality, which is in turn dependent on the competence of both the cytoplasm and nucleus. Here, to improve the efficiency of embryo development from developmentally incompetent oocytes, we performed spindle-chromosome complex transfer (ST) between matured (IVM) and matured (IVO) oocytes of the non-human primate rhesus monkey. We observed that the blastocyst rate of embryos derived from transferring the spindle-chromosome complex (SCC) of IVM oocytes into enucleated IVO oocytes was comparable with that of embryos derived from IVO oocytes. After transferring the reconstructed embryos into the uterus of surrogate mothers, two live rhesus monkeys were obtained, indicating that the nuclei of IVM oocytes support both the pre-and post-implantation embryo development of non-human primates.
PubMed: 37520712
DOI: 10.1016/j.isci.2023.107299 -
Cambridge Quarterly of Healthcare... Mar 2024Can Rawlsian public reason sufficiently justify public policies that regulate or restrain controversial medical and technological interventions in bioethics (and the...
Can Rawlsian public reason sufficiently justify public policies that regulate or restrain controversial medical and technological interventions in bioethics (and the broader social world), such as abortion, physician aid-in-dying, CRISPER-cas9 gene editing of embryos, surrogate mothers, pre-implantation genetic diagnosis of eight-cell embryos, and so on? The first part of this essay briefly explicates the central concepts that define Rawlsian political liberalism. The latter half of this essay then demonstrates how a commitment to Rawlsian public reason can ameliorate (not completely resolve) many of the policy disagreements related to bioethically controversial medical interventions today. The goal of public reason is to reduce the size of the disagreement by eliminating features of the disagreement that violate the norms of public reason. The norms of public reason are those norms that are politically necessary to preserve the liberal, pluralistic, democratic character of this society. What remains is reasonable disagreement to be addressed through normal democratic deliberative processes. Specific issues addressed from a public reason perspective include personal responsibility for excessive health costs, the utility of a metaphysical definition of death for organ transplantation, and the moral status of excess embryos generated through IVF and/or their use in medical research.
PubMed: 38465673
DOI: 10.1017/S0963180124000124 -
Ultrasound in Obstetrics & Gynecology :... Jan 2024Fetal movements are often used as a surrogate for fetal wellbeing. Previous research suggests a link between maternal perception of decreased fetal movements (DFM) and...
OBJECTIVE
Fetal movements are often used as a surrogate for fetal wellbeing. Previous research suggests a link between maternal perception of decreased fetal movements (DFM) and small for gestational age (SGA) infants. The aim of this study was to investigate the association between maternal presentation with DFM and birthweight centile categories at a large Australian perinatal center.
METHODS
This was a 5-year cohort study (January 2016 to October 2020) of non-anomalous singleton infants born at the Mater Mothers' Hospital in Brisbane, Australia at 28 weeks gestation or later. The primary outcome for this study was the rate of DFM by birthweight centile categories. Maternal demographics included age, body mass index, ethnicity, parity, medical conditions, and previous stillbirths. The effect of decreased fetal movements on birthweight centile was evaluated with adjusted multinomial regression models. Adjusted logistic regression models were then used to evaluate whether decreased fetal movements resulted in birthweight centiles <5 and <10. Robust standard errors were used to account for clustering at the patient level. Wald tests, Hosmer and Lemeshow's goodness of fit tests, Akaike's and Bayesian Information Criteria were used to evaluate models.
RESULTS
Over the 5-year study period, 45042 women met the inclusion criteria. Of these, 6690 (14.9%) women presented with DFM. Of the DFM cohort, 80.9% (5411/6690) had only one presentation with DFM, whilst 19.1% (1279/6690) had >2 presentations. The overall stillbirth rate was similar in women with DFM (0.1%, 8/6690) and without DFM (0.1%, 50/38352). There was no difference in rates of DFM (either single or multiple) vs. no DFM and infant birthweight centile categories. There was no association between DFM (either single or multiple) and infant birth weight centile.
CONCLUSION
The results of this study suggest that presentation with DFM is not associated with infant size. Clinicians should consider additional risk factors and the overall clinical context in deciding appropriate management. DFM is not necessarily an indication for an immediate or urgent ultrasound scan to assess fetal size. This article is protected by copyright. All rights reserved.
PubMed: 38237047
DOI: 10.1002/uog.27587 -
The Journal of Pediatrics Dec 2023To assess serial myocardial performance and pulmonary vascular resistance (PVR) in infants of mothers with gestational diabetes mellitus (GDM) over the first year of... (Observational Study)
Observational Study
OBJECTIVE
To assess serial myocardial performance and pulmonary vascular resistance (PVR) in infants of mothers with gestational diabetes mellitus (GDM) over the first year of life.
STUDY DESIGN
This was a prospective, observational study. Echocardiography was performed at birth, 6 months, and 1 year of age. Pulmonary artery acceleration time and left ventricular (LV) eccentricity index provided surrogate measurements of PVR. Biventricular function was assessed by tissue Doppler imaging and deformation analysis.
RESULTS
Fifty infants of mothers with GDM were compared with 50 controls with no difference in gestation (38.9 ± 0.8 weeks vs 39.3 ± 0.9 weeks; P = .05) or birthweight (3.55 ± 0.49 kg vs 3.56 ± 0.41 kg; P = .95). At 1 year of age, the pulmonary artery acceleration time was lower (70 ± 11 vs 79 ± 10; P = .01) in the GDM group. LV global longitudinal strain (24.7 ± 1.9 vs 28.8 ± 1.8 %; P < .01), LV systolic strain rate (1.8 ± 0.2 vs 2.1 ± 0.3 1/s; P < .01), and RV free wall strain (31.1 ± 4.8 vs 34.6 ± 3.9 %; P < .01) were lower in the GDM cohort at 1 year of age (all P values adjusted for gestation, mode of delivery, and maternal body mass index).
CONCLUSIONS
Our findings demonstrate higher indices of PVR and lower biventricular function in infants of mothers with GDM compared with controls at each time point assessed in this study over the first year of life.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Infant; Diabetes, Gestational; Prospective Studies; Echocardiography; Myocardium; Systole; Gestational Age
PubMed: 37517648
DOI: 10.1016/j.jpeds.2023.113645 -
JAMA Nov 2023
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Pregnancy Outcome; Reproductive Techniques, Assisted; Retrospective Studies; Surrogate Mothers
PubMed: 37851614
DOI: 10.1001/jama.2023.11023 -
BMJ (Clinical Research Ed.) Oct 2023
Topics: Humans; Female; Pregnancy; Industry; Surrogate Mothers
PubMed: 37827543
DOI: 10.1136/bmj.p2003 -
Scientific Reports Nov 2023The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic...
The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother's metabolic status on children's telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = - 0.80, p < 0.001) and significant differences were observed on age-adjusted DNAmTL between children born before versus after the maternal bariatric surgery. The associations found between body mass index and body fat percentage with DNAmTL in children born after the surgery were influenced by maternal triglycerides, TG/HDL-C ratio and TyG index. This study reports the impact of maternal bariatric surgery on offspring telomere length. The influence of maternal metabolic status on the association between telomere length and markers of adiposity in children suggests a putative modulating effect of bariatric surgery on the cardiometabolic risk in offspring.
Topics: Child; Female; Humans; Adiposity; Obesity; Bariatric Surgery; Body Mass Index; Telomere; Cardiovascular Diseases
PubMed: 38008763
DOI: 10.1038/s41598-023-47813-2 -
Theriogenology Apr 2024The purpose of this study was to compare the efficiency of the production of cloned transgenic Yucatan miniature pigs (YMPs) using two recipient breeds, i.e., YMPs and...
The purpose of this study was to compare the efficiency of the production of cloned transgenic Yucatan miniature pigs (YMPs) using two recipient breeds, i.e., YMPs and domestic pigs (DPs), under various embryo transfer conditions. We initially assessed the in vitro developmental competence of embryos obtained via somatic cell nuclear transfer (SCNT) from three different transgenic donor cells. No difference was observed among the three groups regarding developmental competence. Furthermore, the cloning efficiency remained consistent among the three groups after the transfer of the SCNT embryos to each surrogate mother. Subsequently, to compare the efficiency of the production of cloned transgenic YMPs between the two recipient breeds using varying parameters, including ovulation status (preovulation and postovulation), duration of in vitro culture (IVC) (incubated within 24 h and 24-48 h), and the number of transferred SCNT embryos (less than and more than 300), we assessed the pregnancy rates, delivery rates, mean offspring counts, and cloning efficiency. Regarding the ovulation status, YMPs exhibited higher pregnancy rates, delivery rates, and cloning efficiency compared with DPs in both statuses. Moreover, the pregnancy rates, delivery rates, and cloning efficiency were affected by the ovulation status in DPs, but not in YMPs. The comparison of IVC duration between groups revealed that YMPs had higher pregnancy rates vs. DPs in both conditions. SCNT embryos cultured for 24-48 h in YMPs yielded higher delivery rates and cloning efficiency compared with those cultured for less than 24 h in DPs. Finally, the analysis based on the number of transferred SCNT embryos showed that both the pregnancy and delivery rates were higher in YMPs vs. DPs. However, the highest average number of offspring was obtained when more than 300 SCNT embryos were transferred into DPs, whereas the cloning efficiency was higher in YMPs vs. DPs. Our results suggest that YMPs are more suitable recipients than are DPs under various conditions for the production of cloned transgenic YMPs.
Topics: Pregnancy; Female; Swine; Animals; Swine, Miniature; Animals, Genetically Modified; Cloning, Organism; Nuclear Transfer Techniques; Embryo Transfer
PubMed: 38330863
DOI: 10.1016/j.theriogenology.2024.01.026 -
Reproductive and Developmental Medicine Mar 2024The uterus is transiently receptive for embryo implantation. It remains to be understood why the uterus does not reject a semi-allogeneic embryo (to the biological...
The uterus is transiently receptive for embryo implantation. It remains to be understood why the uterus does not reject a semi-allogeneic embryo (to the biological mother) or an allogeneic embryo (to a surrogate) for implantation. To gain insights, we examined uterine early response genes approaching embryo attachment on day 3 post coitum (D3) at 22 hours when blue dye reaction, an indication of embryo attachment, had not manifested in mice. C57BL/6 pseudo-pregnant (control) and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis. The self-assembling-manifold () algorithm identified 21,858 unique probesets. Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups. There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change (fc) >1.5 and value <5%. Gene ontology (GO) analysis of the 106 upregulated genes revealed 38 significant GO biological process (GOBP) terms ( <0.05), and 32 (84%) of them were associated with immune responses, with a dominant natural killer (NK) cell activation signature. Among the top eight upregulated protein-coding genes, inactivates retinoic acid (RA) while promotes vitamin A storage, both of which are expected to attenuate RA bioavailability; and play roles in ion transport and transmembrane transport; , , and are involved in immune responses; and is important for kynurenine pathway. Most of these genes or their related pathways have functions in immune regulations. RA signaling has been implicated in immune tolerance and immune homeostasis, and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta. The mechanisms of immune responses approaching embryo attachment remain to be elucidated. The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo.
PubMed: 38404366
DOI: 10.1097/RD9.0000000000000090