LINE-1 methylation in cleft lip tissues:influence of infant MTHFR c.677C>T genotype

Objective: To investigate the influence of MTHFR c.677C>T genotype on LINE-1 methylation in lateral and medial tissues from cleft lip (CL). Methods: Forty-five consecutive non-syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study. Genomic DNA was extracted from tissues at both sides of cleft lip, and LINE-1 methylation was detected by bisulfite conversion and pyrosequencing. MTHFR c.677C>T genotyping was carried out using the TaqMan genotyping assay. Results: LINE-1 methylation level was significantly higher on medial side of cleft lip compared with lateral side (p = 0.001). This difference was not significantly influenced by the case's sex or cleft type. However, MTHFR c.677C>T genotyping revealed that the difference in LINE-1 methylation across cleft lip was restricted to carriers of C allele of MTHFR c.677C>T and was not apparent in TT homozygous cases (p = 0.027). Conclusion: This integrated analysis supports the previous finding of differences in DNA methylation across the two sides of cleft lip and further suggests a possible role of MTHFR c.677C>T genotype in establishing this difference

Polycystic ovary syndrome: A brain disorder characterized by eating problems originating during puberty and adolescence

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Polycystic ovary syndrome (PCOS) is an endocrine condition associated with reproductive and psychiatric disorders, and with obesity. Eating disorders, such as bulimia and recurrent dieting, are also linked to PCOS. They can lead to the epigenetic dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, thereby impacting on ovarian folliculogenesis. We postulate that PCOS is induced by psychological distress and episodes of overeating and/or dieting during puberty and adolescence, when body dissatisfaction and emotional distress are often present. We propose that upregulated activation of the central HPG axis during this period can be epigenetically altered by psychological stressors and by bulimia/recurrent dieting, which are common during adolescence and which can lead to PCOS. This hypothesis is based on events that occur during a largely neglected stage of female reproductive development. To date, most research into the origins of PCOS has focused on the prenatal induction of this disorder, particularly in utero androgenization and the role of anti-Müllerian hormone. Establishing causality in our peripubertal model requires prospective cohort studies from infancy. Mechanistic studies should consider the role of the gut microbiota in addition to the epigenetic regulation of (neuro) hormones. Finally, clinicians should consider the importance of underlying chronic psychological distress and eating disorders in PCOS

First Trimester Maternal Homocysteine and Embryonic and Fetal Growth: The Rotterdam Periconception Cohort

Homocysteine is a marker for derangements in one-carbon metabolism. Elevated homocysteine may represent a causal link between poor maternal nutrition and impaired embryonic and fetal development. We sought to investigate associations between reference range maternal homocysteine and embryonic and fetal growth. We enrolled 1060 singleton pregnancies (555 natural and 505 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies) from November 2010 to December 2020. Embryonic and fetal body and head growth was assessed throughout pregnancy using three-dimensional ultrasound scans and virtual reality techniques. Homocysteine was negatively associated with first trimester embryonic growth in the included population (crown-rump length B −0.023 mm, 95% CI −0.038,−0.007, p = 0.004, embryonic volume B −0.011 cm3, 95% CI −0.018,−0.004, p = 0.003). After stratification for conception mode, this association remained in IVF/ICSI pregnancies with frozen embryo transfer (crown-rump length B −0.051 mm, 95% CI −0.081,−0.023, p < 0.001, embryonic volume B −0.024 cm3, 95% CI −0.039,−0.009, p = 0.001), but not in IVF/ICSI pregnancies with fresh embryo transfer and natural pregnancies. Homocysteine was not associated with longitudinal measurements of head growth in first trimester, nor with second and third trimester fetal growth. Homocysteine in the highest quartile (7.3–14.9 µmol/L) as opposed to the lowest (2.5–5.2 µmol/L) was associated with reduced birth weight in natural pregnancies only (B −51.98 g, 95% CI −88.13,−15.84, p = 0.005). In conclusion, high maternal homocysteine within the reference range is negatively associated with first trimester embryonic growth and birth weight, and the effects of homocysteine are dependent on conception mode

Validation of a semi-quantitative food-frequency questionnaire for dutch pregnant women from the general population using the method or triads

Objective: We aimed to validate a food-frequency questionnaire (FFQ) for Dutch pregnant women, against three 24 h-recalls and blood concentrations of B-vitamins and fatty acids, using the method of triads. Methods: We included 83 pregnant women from the general population of Rotterdam, the Netherlands, at a median gestational age of 15.6 weeks. Participants completed three non-consecutive 24 h-recalls, and subsequently filled out the 293-item FFQ. Participants provided blood samples from which we analyzed serum folate and vitamin B12, as well as red blood cell folate, linoleic acid, and total saturated, monounsaturated, and polyunsaturated fatty acids. Results: Estimated energy intake did not differ between the FFQ and 24 h-recalls. Deattenuated Pearson’s correlation coefficients, between energy-adjusted nutrient intake estimates from the FFQ and the 24 h-recalls, ranged from 0.41 (fat) to 0.88 (fiber) for macronutrients, and were around 0.6 for most micronutrients, except for vitamin E (0.27). Using the triad method, we obtained validity coefficients of 0.86 (95% Confidence Interval (CI) 0.36, 1.00) for serum folate, 0.86 (95% CI 0.18, 1.00) for red blood cell folate, and 1.00 (95% CI 0.42, 1.00) for vitamin B12. Validity coefficients for serum fatty acids ranged from 0.22 to 0.67. Conclusion: This FFQ is a reliable tool for estimating intake of energy, macronutrients, folate and vitamin B1

Preconception maternal gastric bypass surgery and the impact on fetal growth parameters

Background: Bariatric surgery is increasingly performed in women of reproductive age. As bariatric surgery will result in postoperative rapid catabolic weight loss which potentially leads to fetal malnutrition and directly related impaired intra-uterine growth, it is advised to postpone pregnancy for at least 12–18 months after surgery. Objectives: To investigate the consequences of preconception gastric bypass surgery (pGB) on fetal growth parameters and maternal pregnancy outcome. Setting: Maasstad Hospital, The Netherlands, general hospital and Erasmus Medical Center, The Netherlands, university hospital. Methods: We included 97 pGB pregnancies (Maasstad hospital) and 440 non-bariatric pregnancies (Rotterdam Periconception cohort, Erasmus Medical Center). Longitudinal second and third trimester fetal growth parameters (head circumference, biparietal diameter, femur length, abdominal circumference, estimated fetal weight) were analyzed using linear mixed models, adjusting for covariates and possible confounders. Fetal growth and birthweight in pGB pregnancies were compared to non-bariatric pregnancies and Dutch reference curves. Maternal pregnancy outcome in the pGB group was compared to non-bariatric pregnancies. Results: All fetal growth parameters of pGB pregnancies were significantly decreased at 20 weeks’ gestation (P &lt; .001) and throughout the remaining part of pregnancy (P &lt; .05) compared with non-bariatric pregnancies (crude and adjusted models). In our cohort, gestational weight gain was not significantly associated with birthweight corrected for gestational age. Birthweight was significantly lower in pGB pregnancies (estimate –241 grams [95% CI, –342.7 to –140.0]) with a 2-fold increased risk of small-for-gestational-age (SGA) (adjusted odds ratio 2.053 [95% CI, 1.058 to 3.872]). Compared to the non-bariatric pregnancies, we found no significant differences in maternal pregnancy outcome. Conclusions: PGB is associated with overall reduced fetal growth trajectories and a 2-fold increased risk of SGA, without significant adverse consequences for maternal pregnancy outcome. We recommend close monitoring of fetal growth after pGB.</p

ZZ-boson polarization as a model-discrimination analyzer

Determining the spin of any new particle is critical in identifying the true theory among various extensions of the Standard Model (SM). The degree of $Z$-boson polarization in any two-body decay process $A\to B Z$ is sensitive to the spin assignments of two new particles $A$ and $B$. Considering all possible spin-0, 1/2 and 1 combinations in a renormalizable field theory, we demonstrate that $Z$-boson polarization can indeed play a role of a decisive and universal analyzer in distinguishing the different spin assignments.Comment: 10 pages, 3 figures, 1 tabl

Larger First-Trimester Placental Volumetric Parameters Are Associated With Lower Pressure and More Flow-Mediated Vasodilation of the Fetoplacental Vasculature After Delivery

Objective: To explore the correlation between in vivo placental volumetric parameters in the first trimester of pregnancy and ex vivo parameters of fetoplacental vascular function after delivery. Methods: In ten singleton physiological pregnancies, placental volume (PV) and uteroplacental vascular volume (uPVV) were measured offline in three-dimensional ultrasound volumes at 7, 9, and 11 weeks gestational age (GA) using Virtual Organ Analysis and Virtual Reality. Directly postpartum, term placentas were ex vivo dually perfused and pressure in the fetoplacental vasculature was measured to calculate baseline pressure (pressure after a washout period), pressure increase (pressure after a stepwise fetal flow rate increase of 1 mL/min up to 6 mL/min) and flow-mediated vasodilation (FMVD; reduction in inflow hydrostatic pressure on the fetal side at 6 mL/min flow rate). Correlations between in vivo and ex vivo parameters were assessed by Spearman’s correlation coefficients (R). Results: Throu

Prenatal parental tobacco smoking, gene specific DNA methylation, and newborns size: the Generation R study

Background: Deleterious effects of prenatal tobacco smoking on fetal growth and newborn weight are well-established. One of the proposed mechanisms underlying this relationship is alterations in epigenetic programming. We selected 506 newborns from a population-based prospective birth cohort in the Netherlands. Prenatal parental tobacco smoking was assessed using self-reporting questionnaires. Information on birth outcomes was obtained from medical records. The deoxyribonucleic acid (DNA) methylation of the growth genes IGF2DMR and H19 was measured in newborn umbilical cord white blood cells. Associations were assessed between parental tobacco smoking and DNA methylation using linear mixed models and adjusted for potential confounders. Results: The DNA methylation levels of IGF2DMR and H19 in the non-smoking group were median (90 % range), 54.0 % (44.6–62.0), and 30.0 % (25.5–34.0), in the first trimester only smoking group 52.2 % (44.5–61.1) and 30.8 % (27.1–34.1), and in the continued smoking group 51.6 % (43.9–61.3) and 30.2 % (23.7–34.8), respectively. Continued prenatal maternal smoking was inversely associated with IGF2DMR methylation (β = −1.03, 95 % CI −1.76; −0.30) in a dose-dependent manner (P-trend = 0.030). This association seemed to be slightly more profound among newborn girls (β = −1.38, 95 % CI −2.63; −0.14) than boys (β = −0.72, 95 % CI −1.68; 0.24). H19 methylation was also inversely associated continued smoking <5 cigarettes/day (β = −0.96, 95 % CI −1.78; −0.14). Moreover, the association between maternal smoking and newborns small for gestational age seems to be partially explained by IGF2DMR methylation (β = −0.095, 95 % CI −0.249; −0.018). Among non-smoking mothers, paternal tobacco smoking was not associated with IGF2DMR or H19 methylation. Conclusions: Maternal smoking is inversely associated with IGF2DMR methylation in newborns, which can be one of the underlying mechanisms through which smoking affects fetal growth