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14 pages, 649 KB  
Article
Polygenic Risk Score Associated with Gestational Diabetes Mellitus in an AmericanIndian Population
by Karrah Peterson, Camille E. Powe, Quan Sun, Crystal Azure, Tia Azure, Hailey Davis, Kennedy Gourneau, Shyanna LaRocque, Craig Poitra, Sabra Poitra, Shayden Standish, Tyler J. Parisien, Kelsey J. Morin and Lyle G. Best
J. Pers. Med. 2025, 15(9), 395; https://doi.org/10.3390/jpm15090395 - 22 Aug 2025
Viewed by 272
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with GDM, but no clear pathophysiology has been ascertained. Methods: An analysis was conducted on 38 women with and 296 without GDM, within a case/control study of pre-eclampsia. The genetic variants examined were selected from among a published polygenic risk score of 10 variants (PRS-10). Genetic models were evaluated for each variant by multivariate logistic regression methods adjusted for age, body mass index, and pre-eclampsia. Since the genotypes for three of the PRS-10 were not available, a risk score comprising the total risk alleles among seven of the variants (PRS-7) was evaluated among those with all genotypes available. Results: Multivariate logistic regression showed significant, independent, positive associations between body mass index (BMI) and age. The posited PRS-7 showed a trend (OR 1.56, 95% CI 0.92–2.56, p = 0.070), and sensitivity analysis comprising three variants (PRS-3) was significantly associated with GDM (OR 2.43, 95% CI 1.17–5.06, p = 0.017). In univariate analysis, rs1421085 was associated with GDM (OR 0.50, 95% CI 0.26–0.95, p = 0.034), but not after adjustment for covariates, and paradoxically not for the expected risk allele. None of the other six variants showed an individual association with GDM. The previously published meta-analysis of PRS-10 showed a degree of heterogeneity (pQ= 0.03) among the three cohorts analyzed, suggesting that variant effects may differ according to the genetic background, which points to the importance of examining the generalizability of any posited polygenic risk scores. Conclusions: In conclusion, we provide additional support for and further refine the results of a previously published polygenic risk score for GDM in an ethically unrelated population. Full article
(This article belongs to the Section Omics/Informatics)
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16 pages, 481 KB  
Article
Maternal Adherence to Healthy Dietary Patterns During Pregnancy and Gestational Weight Gain
by Shan-Xuan Lim, Siona Wadhawan, Elizabeth A. DeVilbiss, Priscilla K. Clayton, Kathryn A. Wagner, Jessica L. Gleason, Zhen Chen, Cuilin Zhang, Katherine L. Grantz and Jagteshwar Grewal
Nutrients 2025, 17(16), 2707; https://doi.org/10.3390/nu17162707 - 21 Aug 2025
Viewed by 294
Abstract
Background/Objectives: Suboptimal gestational weight gain (GWG) has been linked to increased risks of adverse maternal outcomes. Evidence linking diet in pregnancy to GWG remains limited. We assessed relationships between adherence to five dietary patterns (Planetary Health Diet [PHD], Dietary Approaches to Stop [...] Read more.
Background/Objectives: Suboptimal gestational weight gain (GWG) has been linked to increased risks of adverse maternal outcomes. Evidence linking diet in pregnancy to GWG remains limited. We assessed relationships between adherence to five dietary patterns (Planetary Health Diet [PHD], Dietary Approaches to Stop Hypertension [DASH], Alternate Mediterranean Diet [AMED], Healthy Eating Index [HEI], and Alternate Healthy Eating Index [AHEI]) and 2009 Institute of Medicine GWG categories. Methods: Women expecting singleton pregnancies participated in the NICHD Fetal Growth Studies and completed a food-frequency questionnaire (FFQ) at 8 to 13 weeks of gestation that captured their baseline diet. Adherence to each dietary pattern was calculated, with higher scores indicating greater adherence. Women were categorized into low, moderate or high adherence to each dietary pattern. Using multinomial logistic regression, we estimated adjusted odds ratios and 95% confidence intervals [OR (95% CIs)] of inadequate or excessive GWG (reference category: adequate), for high vs. low adherence to each dietary pattern. Results: In the full cohort, women with high vs. low adherence to DASH, AMED, HEI, or AHEI (but not PHD) had a 13% to 31% lowered odds of inadequate total GWG [ranging from 0.87 (0.58, 1.31) for AMED to 0.69 (0.48, 0.99) for DASH]. High adherence to DASH or HEI was associated with lower odds of inadequate first-trimester GWG, after correcting for multiple testing [DASH: 0.36 (0.22, 0.61), HEI: 0.49 (0.30, 0.79)]. No significant association was observed between any of the dietary patterns and excessive total and trimester-specific GWG. Conclusions: Greater adherence to several dietary patterns was associated with lowered odds of inadequate GWG. Future studies could characterize these diets objectively by identifying metabolite signatures and examining their associations with GWG. Full article
(This article belongs to the Special Issue Maternal Diet, Body Composition and Offspring Health)
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36 pages, 19130 KB  
Article
The Transgenerational Impact of High-Fat Diet and Diabetic Pregnancy on Embryonic Transcriptomics and Mitochondrial Health
by Abigail K. Klein, Benjamin P. Derenge, Malini Mukherjee, Srikrishna P. Reddy, Tricia D. Larsen, Prathapan Ayyappan, Tyler C. T. Gandy, Kyle M. Siemers, Michael S. Kareta and Michelle L. Baack
Biomedicines 2025, 13(8), 2019; https://doi.org/10.3390/biomedicines13082019 - 19 Aug 2025
Viewed by 439
Abstract
Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) [...] Read more.
Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) rat offspring, partially through epigenomic and transcriptomic programming. Primordial germ cells, which become the second generation (F2), are also exposed, which could incite generational risk. This study aimed to determine whether the F2 transcriptome already has genomic variation at the preimplantation embryo stage, and whether variations normalize, persist or compound in the third generation (F3). Methods: F0 female rats were fed a control or HF diet, then DM was induced in HF-fed dams on gestational day (GD)14, exposing F1 offspring and F2 primordial germ cells to hyperlipidemia, hyperglycemia and fetal hyperinsulinemia during the last third of pregnancy. F1 pups were reared by healthy dams and bred to produce F2 embryos (F2e) and F2 pups. F2 offspring were bred to produce F3 embryos (F3e). Embryos were assessed by a novel grading method, live cell imaging, and single-cell RNA sequencing. Results: Embryo grades were not different, but HF+DM F2e had more cells while F3e had fewer cells and overall fewer embryos. HF+DM F2e had similar mitochondria quantity but a downregulation of genes involved in lipid metabolism and more oxidative stress, consistent with mitochondrial dysfunction. They also had an upregulation of chromatin-remodeling genes. The predicted developmental effect is accelerated embryo aging and epigenetic drift. In contrast, HF+DM F3e had an adaptive stress response leading to increased mitochondria quantity and an upregulation of genes involved in mitochondrial respiration, metabolism, and genomic repair that led to a predicted developmental effect of delayed embryo maturation. Conclusions: Although pathways vary, both generations have metabolically linked differentially expressed genes that influence cell fate and developmental pathways. In conclusion, HF+DM pregnancy can program the early embryonic transcriptome for three generations, despite an intergenerational healthy diet. Full article
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17 pages, 2843 KB  
Article
Fatty Acid Profiling of Breast Milk at Different Gestational Ages
by Giuseppe De Bernardo, Giuseppina Leone, Federica Izzo, Marta Giovengo, Manuela Giovanna Basilicata, Fabio Centanni, Francesca Morlino, Emanuela Salviati, Maurizio Giordano, Serafina Perrone, Giuseppe Buonocore, Matteo Delli Carri, Giacomo Pepe and Pietro Campiglia
Nutrients 2025, 17(16), 2672; https://doi.org/10.3390/nu17162672 - 19 Aug 2025
Viewed by 332
Abstract
Background/objectives: This study aimed to characterize the fatty acid (FA) profile of breast milk (BM) at 7 days (T7) and 1 month postpartum (T30) using gas chromatography–mass spectrometry (GC-MS) and to evaluate associations between maternal diet during pregnancy and BM FA composition. Methods [...] Read more.
Background/objectives: This study aimed to characterize the fatty acid (FA) profile of breast milk (BM) at 7 days (T7) and 1 month postpartum (T30) using gas chromatography–mass spectrometry (GC-MS) and to evaluate associations between maternal diet during pregnancy and BM FA composition. Methods: A prospective observational cohort study was conducted from March 2022 to October 2023, involving mothers grouped by gestational age at delivery (32 weeks, 32–36.6 weeks, and >37 weeks). Results: BM lipid profiles were generally similar across gestational groups, with notable differences at T7 in saturated fatty acids (SFAs), myristic acid, monounsaturated fatty acids (MUFAs), erucic acid, nervonic acid, and some FA ratios. At T30, differences persisted in SFAs, MUFAs, myristic acid, and MUFA/SFA. At T7, red meat intake was positively correlated with stearic acid; white meat intake was negatively associated with multiple FAs (including ω-3) but positively with linoleic. Cheese correlated positively with caprylic acid; milk negatively with pentadecylic acid; and dried fruit positively with MUFA. At T30, fish consumption was prevalently positively related to DHA, EPA, and Omega-3, while red meat was positively associated with arachidic acid and margaric acid and negatively with di-homo-gamma linolenic acid. White meat showed a predominantly negative correlation with DHA, EPA and MUFA. Milk intake showed both positive (i.e., caproic acid) and multiple negative FA associations. Cheese was positively associated with caprylic acid, while dried fruit intake was positively linked to oleic acid and MUFA. Conclusions: Despite stable total lipid content, gestational age influenced specific FA profiles. These shifts may reflect adaptive responses to neonatal metabolic and neurodevelopmental needs. Understanding such mechanisms could guide tailored nutritional strategies, especially for preterm infants. Full article
(This article belongs to the Special Issue Nutritional Requirements of Pregnant and Lactating Women)
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17 pages, 2379 KB  
Article
Maternal Extra Virgin Olive Oil Supplementation Enhances Offspring Immune Function: A Preclinical Study
by Sonia Zhan-Dai, Blanca Grases-Pintó, Adriana García-Vara, Ruth Ferrer, Raquel Martín-Venegas, Rosa M. Lamuela-Raventós, Margarida Castell, Francisco J. Pérez-Cano, Anna Vallverdú-Queralt and Maria J. Rodríguez-Lagunas
Int. J. Mol. Sci. 2025, 26(16), 7946; https://doi.org/10.3390/ijms26167946 - 18 Aug 2025
Viewed by 290
Abstract
Maternal diet influences offspring development, immune function, and intestinal health. This study investigates the effects of maternal supplementation with a key component of the Mediterranean Diet, extra virgin olive oil (EVOO), on the immune health of offspring at the end of lactation. Lewis [...] Read more.
Maternal diet influences offspring development, immune function, and intestinal health. This study investigates the effects of maternal supplementation with a key component of the Mediterranean Diet, extra virgin olive oil (EVOO), on the immune health of offspring at the end of lactation. Lewis rat dams received either refined olive oil (ROO), EVOO, or water (REF) during gestation and lactation. Plasma immunoglobulin G2c (IgG2c) concentration was elevated in pups born to EVOO-supplemented mothers, indicating enhanced immune development. Histological analysis of the small intestine revealed more goblet cells in the EVOO group, indicating a potential positive effect on the intestinal barrier function. In vitro assays showed that EVOO metabolites did not display cytotoxicity and had improved barrier integrity under a stress stimulus. These findings suggest that maternal EVOO supplementation may have beneficial effects on immune and intestinal development and health in offspring. Full article
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22 pages, 319 KB  
Article
Determination of the Available Energy of Corn DDGS Fed to Pregnant Sows
by Can Zhang, Bo Cheng, Lei Xue, Ling Liu, Fenglai Wang and Jianjun Zang
Animals 2025, 15(16), 2370; https://doi.org/10.3390/ani15162370 - 12 Aug 2025
Viewed by 220
Abstract
Based on an established appropriate substitution level for corn distillers dried grains with solubles (DDGSs) replacing energy-supplying components in the basal diet for pregnant sows, the substitution method was employed to determine the available energy values of corn DDGSs. In Exp. 1, forty [...] Read more.
Based on an established appropriate substitution level for corn distillers dried grains with solubles (DDGSs) replacing energy-supplying components in the basal diet for pregnant sows, the substitution method was employed to determine the available energy values of corn DDGSs. In Exp. 1, forty pregnant sows (gestation day = 50 ± 5 d; body weight = 220 ± 24.9 kg; parity, 4 to 6) were randomly allocated into five treatments. The control group was fed a corn–soybean basal diet, while test diets contained 20%, 30%, 40%, 50% corn DDGSs replacing the energy-supplying portion of the basal diet. In Exp. 2, the available energy of five corn DDGS sources was determined using the substitution method at a 30% substitution level. Twelve pregnant sows (gestation day = 50 ± 5 d; body weight = 225.4 ± 29.2 kg; parity, 4 to 6) were arranged in a 6 × 3 Youden square design. Dietary treatments consisted of the corn–soybean basic diet and five test diets incorporating different corn DDGS types. Increasing the substitution level of corn DDGSs displayed both linear and quadratic effects (p < 0.05) on the apparent total tract digestibility (ATTD) of dry matter (DM), organic matter (OM), acid detergent fiber (ADF), ether extract (EE) and gross energy (GE) in diets. The ATTD of neutral detergent fiber (NDF), digestible energy (DE) and metabolizable energy (ME) was quadratically affected by different substitution levels (p < 0.05), with the highest value achieved at the 30% substitution level. As the substitution level of corn DDGSs increased, the ATTD of ADF in corn DDGSs decreased. In contrast, the ATTD of crude protein (CP) increased either linearly or quadratically (p < 0.05), and a significant quadratic effect was observed for the ATTD of EE in corn DDGSs (p < 0.05). Although the GE, DE, and ME of corn DDGSs were not significantly influenced by the substitution level, the 30% corn DDGSs resulted in the lowest coefficients of variation (CV). Therefore, a 30% substitution level of corn DDGSs is recommended for energy-supplying components in the basal diet of pregnant sows using the substitution method. The ranges of DE, ME and net energy (NE) of five corn DDGSs samples were 15.58–18.07, 12.17–16.42 and 8.76–15.88 MJ/kg DM, respectively. The absolute value of relative error (|RE|) between the predicted available energy values obtained from the prediction equations established in Exp. 2 and the determined values were below 5%, except for ME for corn DDGSs N3 (5.81%). Full article
(This article belongs to the Special Issue Exploration of Sustainable Feed Resources and Pig Dietary Strategies)
23 pages, 884 KB  
Article
Maternal BMI and Diet Quality Modulate Pregnancy Oxidative and Inflammatory Homeostasis
by Chiara Mandò, Chiara Novielli, Anna Maria Nuzzo, Francesca Parisi, Laura Moretti, Fabrizia Lisso, Alberto Revelli, Valeria M. Savasi, Arianna Laoreti, Gaia M. Anelli, Alessandro Rolfo and Irene Cetin
Nutrients 2025, 17(16), 2590; https://doi.org/10.3390/nu17162590 - 9 Aug 2025
Viewed by 450
Abstract
Background/Objectives: Maternal nutrition and pregestational BMI are critical determinants of pregnancy outcomes. This prospective multicenter observational study investigated the interplay between prepregnancy BMI, dietary patterns, and oxidative/inflammatory status in 153 Italian healthy pregnant women with normal weight (NW), overweight (OW), or obesity (OB). [...] Read more.
Background/Objectives: Maternal nutrition and pregestational BMI are critical determinants of pregnancy outcomes. This prospective multicenter observational study investigated the interplay between prepregnancy BMI, dietary patterns, and oxidative/inflammatory status in 153 Italian healthy pregnant women with normal weight (NW), overweight (OW), or obesity (OB). Methods: Detailed clinical, biochemical, placental, and neonatal data were measured at third trimester and delivery. Dietary intake was assessed via a validated questionnaire, and dietary patterns were derived using principal component analysis. Results: OW and OB women had significantly higher levels of inflammatory (CRP, hepcidin) and oxidative stress biomarkers (DNA/RNA damage, catalase activity) than NW. Multivariate models confirmed independent associations between BMI and these biomarkers (CRP: β = 0.297, p = 0.000; hepcidin: β = 1.419, p = 0.006; DNA/RNA damage: β = 409.9, p = 0.000; catalase activity: β = 1.536, p = 0.000). Superoxide dismutase activity and total antioxidant capacity were not associated with BMI. Nutritional intake across BMI groups was largely suboptimal relative to national recommendations, with insufficient levels of polyunsaturated fats and key micronutrients. Four dietary patterns were identified, with adherence varying by BMI. A “prudent-style” pattern (high plant, low animal) was positively associated with gestational age (β = 0.243, p = 0.033) and inversely with neonatal head circumference (β = −0.414, p = 0.050). A “Western-like” pattern (high sugars, snacks, animal fats) was linked to reduced maternal ferritin (β = −2.093, p = 0.036) and increased neonatal head circumference (β = 0.403, p = 0.036). However, not all deviations from the “prudent-style” pattern were metabolically equivalent: while Pattern 3 (high-protein, carbohydrate) may offer partial protective effects, Pattern 4 (moderate protein/plant/sugar) displayed elements of nutritional imbalance with signs of placental inefficiency (β = −0.384, p = 0.023). Conclusions: These findings underscore the dual impact of maternal BMI and diet quality on oxidative-inflammatory balance and perinatal outcomes, supporting the need for early, individualized nutritional strategies in pregnancy. This is further emphasized by the variability in dietary adherence across BMI categories. Full article
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18 pages, 2678 KB  
Article
Pre-Conception Maternal Obesity Confers Autism Spectrum Disorder-like Behaviors in Mice Offspring Through Neuroepigenetic Dysregulation
by Nina P. Allan, Amada Torres, Michael J. Corley, Brennan Y. Yamamoto, Chantell Balaan, Yasuhiro Yamauchi, Rafael Peres, Yujia Qin, Vedbar S. Khadka, Youping Deng, Monika A. Ward and Alika K. Maunakea
Cells 2025, 14(15), 1201; https://doi.org/10.3390/cells14151201 - 5 Aug 2025
Viewed by 1643
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we [...] Read more.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity. We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes. These phenotypes were absent in female offspring and those exposed only during gestation. Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding. This pattern was specific to mice with ASD-like behaviors. Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Autism Spectrum Disorder)
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19 pages, 1016 KB  
Article
Genetic Associations of ITGB3, FGG, GP1BA, PECAM1, and PEAR1 Polymorphisms and the Platelet Activation Pathway with Recurrent Pregnancy Loss in the Korean Population
by Eun Ju Ko, Eun Hee Ahn, Hyeon Woo Park, Jae Hyun Lee, Da Hwan Kim, Young Ran Kim, Ji Hyang Kim and Nam Keun Kim
Int. J. Mol. Sci. 2025, 26(15), 7505; https://doi.org/10.3390/ijms26157505 - 3 Aug 2025
Viewed by 443
Abstract
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women [...] Read more.
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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12 pages, 1252 KB  
Article
Low Dietary Folate Increases Developmental Delays in the Litters of Mthfr677TT Mice
by Karen E. Christensen, Marie-Lou Faquette, Vafa Keser, Alaina M. Reagan, Aaron T. Gebert, Teodoro Bottiglieri, Gareth R. Howell and Rima Rozen
Nutrients 2025, 17(15), 2536; https://doi.org/10.3390/nu17152536 - 1 Aug 2025
Viewed by 441
Abstract
Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr677C>T [...] Read more.
Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr677C>T mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice. Methods: Female 677CC (mCC) and 677TT (mTT) mice were fed control (2 mg folic acid/kg (2D)), 1 mg folic acid/kg (1D) and 0.3 mg folic acid/kg (0.3D) diets before and during pregnancy. Embryos and maternal tissues were collected at embryonic day 10.5. Embryos were examined for developmental delays and defects. Methyltetrahydrofolate (methylTHF) and total homocysteine (tHcy) were measured in maternal plasma, and MTHFR protein expression was evaluated in maternal liver. Results: MethylTHF decreased due to the experimental diets and mTT genotype. tHcy increased due to 0.3D and mTT genotype; mTT 0.3D mice had significantly higher tHcy than the other groups. MTHFR expression was lower in mTT liver than mCC. MTHFR protein expression increased due to low folate diets in mCC mice, whereas in mTT mice, MTHFR expression increased only due to 1D. Developmental delays were increased in the litters of mTT mice fed 1D and 0.3D. Conclusions: The Mthfr677C>T mouse models the effects of the MTHFR 677TT genotype in humans and provides a folate-responsive model for examination of the effects of folate intake and the MTHFR 677C>T variant during gestation. Full article
(This article belongs to the Section Micronutrients and Human Health)
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14 pages, 635 KB  
Article
Sweet and Fat Taste Perception: Impact on Dietary Intake in Diabetic Pregnant Women—A Cross-Sectional Observational Study
by Inchirah Karmous, Rym Ben Othman, Ismail Dergaa, Halil İbrahim Ceylan, Cyrine Bey, Wissem Dhahbi, Amira Sayed Khan, Henda Jamoussi, Raul Ioan Muntean and Naim Akhtar Khan
Nutrients 2025, 17(15), 2515; https://doi.org/10.3390/nu17152515 - 31 Jul 2025
Viewed by 559
Abstract
Background: Taste changes are common during pregnancy and can have a significant impact on dietary habits. Objective: This study aimed to investigate the influence of the perception of sweet and fat taste on diet in pregnant diabetic women. Methods: This [...] Read more.
Background: Taste changes are common during pregnancy and can have a significant impact on dietary habits. Objective: This study aimed to investigate the influence of the perception of sweet and fat taste on diet in pregnant diabetic women. Methods: This cross-sectional observational study included 66 pregnant women, 33 with gestational diabetes and 33 with pre-gestational type 2 diabetes. Taste perception tests were conducted to evaluate thresholds for detecting sweet and fatty tastes. Dietary surveys were used to assess daily nutrient intake, and various biochemical parameters, such as glycemia, HbA1c, and cholesterol, were analyzed. Results: The low-fat taster group (threshold > 0.75 mmol/L) included more patients with diabetes compared to those with gestational diabetes. All diabetic patients had low sucrose perception. Although pregnant women with gestational diabetes detected sweetness at high concentrations, pregnant women with diabetes detected it at lower concentrations (0.012 ± 0.023 mmol/L vs. 0.006 ± 0.005 mmol/L; p = 0.3). High-fat tasters exhibited elevated glycemia compared to low-fat tasters (6.04 ± 1.88 mmol/L vs. 7.47 ± 3.4 mmol/L; p = 0.03). They also had higher cholesterol (p = 0.04) and lower HDL-C levels (4.96 ± 1.04 mmol/L vs. 1.36 ± 0.29 mmol/L; p = 0.03). High-fat tasters showed more frequent daily consumption of oil, butter, cheese, and chocolate. The highly sweet tasters had higher cholesterol levels and lower LDL levels. Individuals who reported being highly sensitive to sweet taste consumed more daily oil, sweetened yogurt, or cream desserts, as well as white sugar. Conclusions: These findings indicate that altered sensitivity to fat and sweet tastes is associated with different dietary habits and metabolic profiles in pregnant women with diabetes. Specifically, reduced sensitivity to the taste of fat is associated with higher consumption of high-fat foods and poorer lipid profiles. In contrast, sensitivity to sweet taste correlates with an increased intake of sugary and fatty foods. Understanding these taste-related behaviors can help develop personalized nutritional strategies to improve metabolic control and maternal–fetal outcomes in this high-risk group. Full article
(This article belongs to the Section Nutrition and Diabetes)
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27 pages, 2012 KB  
Article
Dual Effects of Maternal Diet and Perinatal Organophosphate Flame Retardant Treatment on Offspring Development, Behavior and Metabolism
by Ali Yasrebi, Catherine M. Rojas, Shabree Anthony, Samantha Feltri, Jamilah Evelyn, Kimberly Wiersielis, Samantha Adams, Veronia Basaly, Grace L. Guo, Lauren M. Aleksunes and Troy A. Roepke
Toxics 2025, 13(8), 639; https://doi.org/10.3390/toxics13080639 - 29 Jul 2025
Viewed by 413
Abstract
The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) [...] Read more.
The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article
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18 pages, 305 KB  
Review
Causes of Childhood Cancer: A Review of Literature (2014–2021): Part 2—Pregnancy and Birth-Related Factors
by Rebecca T. Emeny, Angela M. Ricci, Linda Titus, Alexandra Morgan, Pamela J. Bagley, Heather B. Blunt, Mary E. Butow, Jennifer A. Alford-Teaster, Raymond R. Walston III and Judy R. Rees
Cancers 2025, 17(15), 2499; https://doi.org/10.3390/cancers17152499 - 29 Jul 2025
Viewed by 1030
Abstract
Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. [...] Read more.
Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. Results: Strong evidence links increased risk of childhood cancer with maternal diabetes, age, and alcohol and coffee consumption during pregnancy. Both paternal and maternal cigarette smoking before and during pregnancy are associated with childhood cancers. Diethylstilbestrol (DES) exposure in utero has long been known to be causally associated with increased risk of vaginal/cervical cancers in adolescent girls. More recent evidence implicates in utero DES exposure to testicular cancer in young men and possible intergenerational effects on ovarian cancer in the granddaughters of women exposed to DES during pregnancy. There is strong evidence that childhood cancer risk is also associated with both high and very low birth weight and with gestational age. Evidence is also strong for the protective effects of maternal vitamin consumption and a healthy diet during pregnancy. Unlike early studies, those reviewed here show no association between in utero exposure to medical ionizing radiation, which may be explained by reductions over time in radiation doses, avoidance of radiation during pregnancy, and/or by inadequate statistical power to detect small increases in risk, rather than a lack of causal association. Evidence is mixed or conflicting for an association between childhood cancer and maternal obesity, birth order, cesarean/instrumental delivery, and prenatal exposure to diagnostic medical radiation. Evidence is weak or absent for associations between childhood cancer and multiple gestations or assisted reproductive therapies, as well as prenatal exposure to hormones other than DES, and medications. Full article
19 pages, 4491 KB  
Article
Temporal Dynamics of Fecal Microbiome and Short-Chain Fatty Acids in Sows from Early Pregnancy to Weaning
by Sui Liufu, Xin Xu, Qun Lan, Bohe Chen, Kaiming Wang, Lanlin Xiao, Wenwu Chen, Wu Wen, Caihong Liu, Lei Yi, Jingwen Liu, Xianchuang Fu and Haiming Ma
Animals 2025, 15(15), 2209; https://doi.org/10.3390/ani15152209 - 27 Jul 2025
Viewed by 369
Abstract
Although age-related changes in the gut microbiome of pigs have been extensively studied, the dynamic patterns of fecal microbiota and SCFAs during the gestation-to-weaning period in sows remain poorly characterized. We aim to characterize the changes in fecal microbiota and SCFAs from pregnancy [...] Read more.
Although age-related changes in the gut microbiome of pigs have been extensively studied, the dynamic patterns of fecal microbiota and SCFAs during the gestation-to-weaning period in sows remain poorly characterized. We aim to characterize the changes in fecal microbiota and SCFAs from pregnancy to weaning, and to investigate their associations with maternal weight gain during gestation. We systematically collected 100 fecal samples at four time points (day 30 of pregnancy (T1), 1–2 days before delivery (T2), day 10 after delivery (T3), and day 21 of weaning stage (T3)), and measured the body weight of sows at T1 (132 kg ± 10.8) and T2 (205 kg ± 12.1). The primary nutrient components of the diets during the gestation and lactation periods are summarized. All fecal samples were subjected to 16S rRNA gene sequencing. We found that a high proportion of crude fiber (bran) is a key feature of the gestation diet, which may affect enterotype shifts and gut microbial composition. Sows fed a high-fiber diet showed significant enrichment of gut microbiota, including genera such as Prevotellaceae_UCG-003, Prevotellaceae_NK3B31_group, and Prevotella_9 during the gestational period (LDA score > 2). Moreover, Eubacterium_coprostanoligenes_group (average relative abundance: 5.5%) and Lachnospiraceae_NK4A136_group (average relative abundance: 2.5%) were the dominant bacteria during the lactation stage. Fecal propionate and butyrate levels were lowest in late gestation, and propionate negatively and acetate positively correlated with body weight change (p < 0.05). Additionally, certain Prevotella taxa were associated with arachidonic acid metabolism and acetate production (p < 0.05). Our study identified key microbial communities across four stages from gestation to weaning and revealed that dietary patterns can shape the sow gut microbiota. Furthermore, we observed significant correlations between SCFAs and body weight change during pregnancy. These findings provide a scientific basis and theoretical support for future strategies aimed at modulating gut microbiota and targeting SCFAs to improve maternal health and productivity throughout the gestation-to-weaning period. Full article
(This article belongs to the Section Pigs)
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14 pages, 336 KB  
Article
Testing the Development of a Diet-Based Bisphenol a Score to Facilitate Studies on Child Neurodevelopment: A Pilot Project
by Marisa A. Patti, Apollo Kivumbi, Juliette Rando, Ashley Song, Lisa A. Croen, Rebecca J. Schmidt, Heather E. Volk and Kristen Lyall
Int. J. Environ. Res. Public Health 2025, 22(8), 1174; https://doi.org/10.3390/ijerph22081174 - 25 Jul 2025
Viewed by 463
Abstract
While gestational Bisphenol A (BPA) exposure has been associated with autism, limited work has focused on dietary sources. Here, we sought to develop a summary metric to capture dietary exposure specifically and test its associations with measured levels, as well as child traits [...] Read more.
While gestational Bisphenol A (BPA) exposure has been associated with autism, limited work has focused on dietary sources. Here, we sought to develop a summary metric to capture dietary exposure specifically and test its associations with measured levels, as well as child traits related to autism. Participants (n = 116) were from the Early Autism Risk Longitudinal Investigation (EARLI) Study, which recruited pregnant women who previously had a child diagnosed with autism. Maternal concentrations of BPA were quantified in urine, and dietary sources of BPA were ascertained via food frequency questionnaires during gestation. A novel BPA “dietary burden score” was developed based on reported intake of foods known to contribute to BPA exposure (i.e., canned foods) from a Dietary History Questionnaire modified for pregnancy. Child autism-related traits were assessed via the Social Responsiveness Scale (SRS-2). We examined associations between BPA biomarkers, dietary burden scores, and child SRS scores. Dietary burden scores were weakly correlated with urinary BPA concentrations (R = 0.19, p = 0.05) but were not associated with child SRS scores. Our work suggests that more detailed dietary assessments may be needed to fully capture diet-based BPA exposures and address diet as a modifiable source of chemical exposure to reduce associated health impacts of BPA. Full article
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