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Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). We found in previous studies that sera from SLE/APS patients when used as a culture medium for rat embryos were found to reduce embryonic growth and development, induce a high rate of embryonic anomalies and death and damage the yolk sac morphologically and functionally.In order to investigate the direct effect of IgG purified from women with SLE/APS on the growth and viability of embryos, we cultured 11.5-day-old rat embryos in their yolk sacs in the presence of IgG purified from SLE/APS patients with recurrent pregnancy loss (RPL). The IgG affected directly the embryo and yolk sac, reducing their growth. The purified IgG positive for anticardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies but positive for antiphosphatydilserine and for antilaminin. Monoclonal antiphosphatydilserine reduced yolk sac growth but the embryos remained intact. Following the observed damage to the yolk sac we cultured human placental explants at 5.5-8 weeks of pregnancy in sera from SLE/APS patients for 96 hours and found that these sera reduced placental trophoblastic cell growth, reduced their proliferation rate and increased their rate of apoptosis. Successful treatment of the women resulted in a correction of the damage induced in the cultured rat embryos and in the cultured placental explants. [ABSTRACT FROM AUTHOR]

Background: Polyethylene wear debris, and the resulting inflammatory response leading to osteolysis and loosening, is the primary mode of failure limiting the longevity of total hip replacements. Alternative bearing surfaces, including ceramic-on-polyethylene, have been investigated in an effort to decrease the amount of polyethylene wear debris. The purpose of this study was to evaluate the seventeen to twenty-one-year results of the use of ceramic-on-polyethylene total hip prostheses.Methods: Sixty-four total hip prostheses were implanted with cement, by one surgeon, in fifty-six patients from 1978 to 1981. The average age at the index arthroplasty was sixty-nine years (range, fifty-one to eighty-four years). The components consisted of a cemented Charnley-Müller stem with a 32-mm modular alumina femoral head and a cemented all-polyethylene acetabular component. All patients who retained the index prosthesis were assessed clinically with use of Harris hip scores and were evaluated radiographically at the time of the latest follow-up.Results: At the time of this latest follow-up, of the original sixty-four implants, eighteen (28%) were still in place and five (8%) had been revised. The remaining forty-one implants were in patients who had died and were functioning well until the patient's death. No patient was lost to follow-up. Of the eighteen hips with an intact prosthesis in the surviving patients, seven had an excellent clinical result; nine, a good result; and two, a fair result. One asymptomatic hip had definite radiographic evidence of femoral loosening. No hip had definite signs of acetabular loosening or evidence of osteolysis. Survivorship analysis revealed that the probability of survival of the prostheses without revision was 95% at five years, 95% at ten years, 89% at fifteen years, and 79% at twenty years. The mean linear and volumetric polyethylene wear rates were 0.034 mm/yr and 28 mm(3)/yr, respectively. There were no fractures of the ceramic heads.Conclusions: Outstanding long-term clinical and radiographic results were attained despite the use of what are now considered substandard techniques (an inferior stem design, a 32-mm head, and first-generation cementing techniques). The wear rates in this study are lower than previously reported metal-on-polyethylene wear rates and are consistent with the lowest reported in vivo ceramic-on-polyethylene wear rates. These findings support the consideration of ceramic-on-polyethylene bearing surfaces in total hip arthroplasty. [ABSTRACT FROM AUTHOR]

Prenatal glucocorticoid exposure has been negatively associated with infant neurocognitive outcomes. However, questions about developmental timing effects across gestation remain. Participants were 253 mother-child dyads who participated in a prospective cohort study recruited in the first trimester of pregnancy. Diurnal cortisol was measured in maternal saliva samples collected across a single day within each trimester of pregnancy. Children (49.8% female) completed the Bayley Mental Development Scales, Third Edition at 6, 12, and 24 months and completed three observational executive function tasks at 24 months. Structural equation models adjusting for sociodemographic covariates were used to test study hypotheses. There was significant evidence for timing sensitivity. First-trimester diurnal cortisol (area under the curve) was negatively associated with cognitive and language development at 12 months and poorer inhibition at 24 months. Second-trimester cortisol exposure was negatively associated with language scores at 24 months. Third-trimester cortisol positively predicted performance in shifting between task rules (set shifting) at 24 months. Associations were not reliably moderated by child sex. Findings suggest that neurocognitive development is sensitive to prenatal glucocorticoid exposure as early as the first trimester and underscore the importance of assessing developmental timing in research on prenatal exposures for child health outcomes.

Fear reactivity is an early emerging temperament trait that predicts longer term behavioral and health outcomes. The current analysis tests the hypothesis, an extension of prior research on maternal immune activation (MIA), that the prenatal maternal immune system is a reliable predictor of observed fear reactivity in infancy. The analysis is based on a prospective longitudinal cohort study that collected data from the first trimester and conducted observational assessments of temperament at approximately 12 months of age ( n = 281 infants). MIA was assessed from immune biomarkers measured in maternal blood at each trimester; infant temperament was assessed using the Laboratory Temperament Assessment Battery assessment at 12 months; covariates included family and sociodemographic factors. Patterns of inflammatory markers across gestation reliably predicted observed temperament: elevated prenatal MIA was associated with high fear reactivity to novel stimuli. The findings provide novel evidence of prenatal origins of fear reactivity and suggest developmental mechanisms that may underlie early emerging individual differences in child temperament. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Air pollution exposure during pregnancy has been associated with numerous adverse pregnancy, birth, and child health outcomes. One proposed mechanism underlying these associations is maternal immune activation and dysregulation. We examined associations between PM 2.5 and NO 2 exposure during pregnancy and immune markers within immune function groups (TH1, TH2, TH17, Innate/Early Activation, Regulatory, Homeostatic, and Proinflammatory), and examined whether those associations changed across pregnancy., Methods: In a pregnancy cohort study (n = 290) in Rochester, New York, we measured immune markers (using Luminex) in maternal plasma up to 3 times during pregnancy. We estimated ambient PM 2.5 and NO 2 concentrations at participants' home addresses using a spatial-temporal model. Using mixed effects models, we estimated changes in immune marker concentrations associated with interquartile range increases in PM 2.5 (2.88 μg/m 3 ) and NO 2 (7.82 ppb) 0-6 days before blood collection, and assessed whether associations were different in early, mid, and late pregnancy., Results: Increased NO 2 concentrations were associated with higher maternal immune markers, with associations observed across TH1, TH2, TH17, Regulatory, and Homeostatic groups of immune markers. Furthermore, the largest increases in immune markers associated with each 7.82 ppb increase in NO 2 concentration were in late pregnancy (e.g., IL-23 = 0.26 pg/ml, 95% CI = 0.07, 0.46) compared to early pregnancy (e.g., IL-23 = 0.08 pg/ml, 95% CI = -0.11, 0.26)., Conclusions: Results were suggestive of NO 2 -related immune activation. Increases in effect sizes from early to mid to late pregnancy may be due to changes in immune function over the course of pregnancy. These findings provide a basis for immune activation as a mechanism for previously observed associations between air pollution exposure during pregnancy and reduced birthweight, fetal growth restriction, and pregnancy complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite the growing body of research suggesting certain pedagogical approaches that can support student well-being, higher education has not fully embraced these approaches and typically still does not view well-being as a high priority in comparison with other metrics such as retention or GPA. Here, we contend that universities must play an active role in supporting lifelong well-being in their student populations by expanding their definitions of student success and providing opportunities and programs that support elements related to well-being. We propose a student well-being nexus, which comprises a sense of belonging, agency, purpose, identity, civic engagement, and financial well-being. This article provides a perspective on the importance of each element to well-being and which pedagogical practices have been shown to support various dimensions of well-being in undergraduate education, such as service learning, undergraduate research, and mentoring. In addition, it showcases 6 exceptional initiatives from various universities that aim to support one or more of the student well-being nexus dimensions, which can serve as models for other universities. Finally, several guiding principles are outlined for higher education institutions to support the implementation of student well-being initiatives and transformational learning opportunities. These include assessment of initiatives, embedding initiatives into the curriculum, and avoidance of creating additional financial burdens for students. These efforts can promote well-being on college campuses and beyond graduation., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Therefore, identifying sources of individual differences in the vaginal microbiome is of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individual's experience of affective symptoms and stress exposure., Methods: Data were based on a prospective longitudinal study of a medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34-40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community clusters (CC1-3) based on dissimilarity of vaginal microbiota composition., Results: Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CC3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CC1-3 and individual taxa, including biosynthetic pathways for serotonin and dopamine. We did not find robust evidence linking symptom- and stress-related biomarkers and CCs., Conclusions: Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM 2.5 ), and nitrogen dioxide (NO 2 ). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM 2.5 , NO 2 , and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM 2.5 concentration (3.20 μg/m 3 ) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM 2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM 2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO 2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM 2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Epidemiologic evidence has emerged showing an association between exposure to air pollution and increased risks of gestational diabetes mellitus (GDM). This study examines the effect of low-level air pollution exposure on a subclinical biomarker of hyperglycemia (i.e., HbA1c) in pregnant people without diabetes before conception. We measured HbA1c in 577 samples repeatedly collected from 224 pregnant people in Rochester, NY, and estimated residential concentrations of PM 2.5 and NO 2 using high-resolution spatiotemporal models. We observed a U-shaped trajectory of HbA1c during pregnancy with average HbA1c levels of 5.13 (±0.52), 4.97 (±0.54), and 5.43 (±0.40)% in early-, mid-, and late pregnancy, respectively. After adjustment for the U-shaped trajectory and classic GDM risk factors, each interquartile range increase in 10 week NO 2 concentration (8.0 ppb) was associated with 0.09% (95% CI: 0.02 to 0.16%) and 0.18% (95% CI: 0.08 to 0.28%) increases in HbA1c over the entire pregnancy and in late pregnancy, respectively. These associations remained robust among participants without GDM. Using separate distributed lag models, we identified a period between 8th and 14th gestational weeks as critical windows responsible for increased levels of HbA1c measured at 14th, 22nd, and 30th gestational weeks. Our results suggest that low-level air pollution contributes to hyperglycemia in medically low-risk pregnant people.

Introduction: Chronic placental inflammation is a routinely diagnosed group of placental lesions that reflect immunologic dysfunction of the mother, fetus, or both., Methods: Complete placental pathology examinations were performed for all term births at New York Presbyterian- Brooklyn Methodist Hospital from January 2010-August 2016. Diagnoses were blinded except to gestational age. CPI lesions were marked as chronic choriodeciduitis, decidual plasma cells, chronic inflammation of basal plate with anchoring villitis, and chronic villitis., Results: In this cohort of term pregnancies, 257 (11.6 %) males and 218 (9.8 %) females had ≥1 CPI lesions. Chronic villitis was the most common (319 or 14 %), with chronic choriodeciduitis, decidual plasma cells, and chronic inflammation of basal plate with anchoring villitis in 94 (4 %), 69 (3 %) and 170 (8 %), respectively. In males, chronic villitis was associated with lower gestational adjusted birthweight and had no association with placental weight. In females, chronic villitis was associated with lower gestational adjusted birthweight, but the effect became nonsignificant after adjustment for placental weight., Discussion: In summary, CPI lesions' incidence and association with birth weight vary by sex. Chronic villitis is associated with lower birthweight in females; this effect is completely mediated by placental weight. Chronic villitis showed a weak direct association of chronic villitis in males, but no association with lower placental weight in males. We suggest that differences between our results and previous publications reflect effects of sampling bias., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carolyn Salafia reports financial support was provided by National Institute of Environmental Health Sciences. The grant ID # is ES029281. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The impacts of prenatal maternal affective symptoms on the placental structure are not well-established. Employing Geographic Information System (GIS) spatial autocorrelation, Moran's I, can help characterize placental thickness uniformity/variability and evaluate the impacts of maternal distress on placental topography., Methods: This study (N = 126) utilized cohort data on prenatal maternal affective symptoms and placental 2D and 3D morphology. Prenatal maternal depression, stress, anxiety and sleep quality were scored for each trimester using the Edinburgh Postnatal Depression Scale (EPDS), Stressful Life Event Scale (SLE), Penn State Worry Questionnaire (PSWQ), and Pittsburgh Sleep Quality Index (PSQI), respectively. Placental shape was divided into Voronoi cells and thickness variability among these cells was computed using Moran's I for 4-nearest neighbors and neighbors within a 10 cm radius. Sex-stratified Spearman correlations and linear regression were used to study associations between mean placental thickness, placental GIS variables, placental weight and the average score of each maternal variable., Results: For mothers carrying boys, poor sleep was associated with higher mean thickness (r = 0.308,p = 0.035) and lower placental thickness uniformity (r = -0.36,p = 0.012). Lower placental weight (r = 0.395,p = 0.003), higher maternal depression (r = -0.318,p = 0.019) and worry/anxiety (r = -0.362,p = 0.007) were associated with lower placental thickness uniformity for mothers carrying girls., Limitations: The study is exploratory and not all GIS models were developed. Excluding high-risk pregnancies prevented investigating pregnancy complications related hypotheses. A larger sample size is needed for greater confidence for clinical application., Conclusions: Placental topography can be studied using GIS theory and has shown that prenatal maternal affective symptoms and sleep have sex-specific associations with placental thickness., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Millennials have been shown to have distinctly different behaviors; however, factors affecting their liking of beef, pork and chicken has not been fully elucidated. As millennials are current and future animal protein consumers, the question of if they have different drivers of liking for beef, pork, and chicken has not been answered. Top loin steaks cooked to 58.3 or 80 °C; and pork loin chops and chicken breasts cooked to 62.7 or 80 °C were cooked on a flat grill. Beef bottom round roasts cooked to 58.3 or 80°; and pork inside ham roasts and chicken thighs were cooked to 62.7 or 80 °C in a Crock-pot®. A descriptive flavor and texture attribute panel and a consumer central location test in four cities were used to evaluated flavor and texture attributes. Consumers were either millennials or non-millennials, and light or heavy beef-eaters. Meat descriptive flavor and texture attributes differed by cooking method, cut, and internal temperature (P < 0.05). Consumers preferred grilled meat more than meat cooked in the Crock-pot® (P > 0.05). Consumers rated grill flavor, juiciness, and tenderness (P ≥ 0.05) higher in grilled meat. Light beef-eaters, those who ate beef 2 to 4 times per month, rated overall, flavor, and species flavor lower (P < 0.05) than heavy beef-eaters, but consumers liked beef regardless of generational segment or their consumption of beef; however, millennials rated overall, overall flavor, and tenderness liking slightly lower than non-millennials. These results indicate that millennials have similar drivers of liking as non-millennials across beef, pork, and chicken protein sources., Competing Interests: Declaration of competing interest We declare no conflict of interest associated with this publication and no financial support for this work that could have influenced the outcome. As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Restricted fetal growth (RFG) is a leading contributor to perinatal mortality and has been associated with gestational exposure to air pollution, such as fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and polycyclic aromatic hydrocarbons (PAHs). This study examines the association between trimester-specific and weekly means of air pollution throughout gestation and placental inflammatory markers at delivery. In a prospective cohort study of 263 pregnant women in Rochester, NY, we measured interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in placental tissue and estimated gestational exposure to PM 2.5 and NO 2 using a high-resolution spatial-temporal model. Exposure to PAHs was estimated using urinary 1-hydroxypyrene (1-OHP) concentrations collected once per trimester. Using distributed lag models with a penalized spline function, each interquartile range (2.6 μg/m 3 ) increase in PM 2.5 concentration during gestational weeks 6-11 was associated with decreased placental IL-6 levels (-22.2%, 95% CI: -39.0%, -0.64%). Using multiple linear regression models, each interquartile range increase of 1-OHP was associated with an increase in TNF-α in the first trimester (58.5%, 95% CI: 20.7%, 74.2%), third trimester (22.9%, 95% CI: 0.04%, 49.5%), and entire pregnancy (29.6%, 95%CI: 3.9%,60.6%). Our results suggest gestational exposure to air pollution may alter the inflammatory environment of the placenta at delivery., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and American Chemical Society.)

Poor sleep quality and psychological distress in pregnancy are important health concerns. Serotonin and melatonin levels may underlie variation in these adverse outcomes. In this study, we examined dietary nutrients involved in serotonin and melatonin synthesis in relation to maternal sleep quality and affective symptoms during pregnancy. Pregnant women at no greater than normal medical risk at enrollment completed 24-hour dietary recalls in mid-late pregnancy. Usual intakes of vitamin B6, vitamin D, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and tryptophan were estimated from dietary intake of foods and supplements using the National Cancer Institute (NCI) method. Sleep quality, depression, and anxiety were measured using validated questionnaires. Associations between nutrient intakes, sleep quality, and affective symptoms were estimated using generalized estimating equation models adjusting for potential confounding factors. In minimally adjusted models, EPA + DHA and tryptophan intakes were associated with a lower score indicating better sleep quality ( b : -1.07, 95% CI: -2.09, -0.05) and ( b : -12.40, 95% CI: -24.60, -0.21), respectively. EPA + DHA and tryptophan intakes were also associated with a lower odds of shorter sleep duration and sleep disturbances. In addition, tryptophan was associated with a lower odds of higher sleep latency. However, associations were attenuated and nonsignificant after adjustment for demographic and lifestyle factors. In conclusion, intakes of EPA + DHA and tryptophan were associated with improved sleep quality, but these associations were confounded by maternal demographic and lifestyle characteristics. This study highlights the need to consider dietary intake and pregnancy health in the context of demographic characteristics and lifestyle behaviors., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Amber Kautz et al.)

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17β-estradiol (E2), they interact with estrogen receptors α/β earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study was conducted to evaluate the effects of relative humidity (RH) on moisture loss and flavor in dry-aged beef. Sixteen strip loins were assigned to one of the four aging treatments: vacuum (WET), dry-aging at 50% RH, dry-aging at 70% RH, or dry-aging at 85% RH and aged for 42 days at 2 °C. Loins were evaluated for evaporation loss, trim loss, tenderness, sensory, and microbiological characteristics. Results show that lower RH results in accelerated moisture loss during the first 3 days of the aging process without significantly affecting the total amount of moisture loss. Pseudomonadales dominated the aerobically dry-aged loins while Enterobacteriales was the most abundant in the wet-aged samples. Dry-aged samples had increased content of free amino acids in the cooked meat juice compared to the wet-aged counterpart. Dry aging at 50% RH tended to associate with more desirable flavor notes., Competing Interests: Declaration of competing interest None. There are no potential conflicts., (Published by Elsevier Ltd.)

Background: Maternal exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitous constituents of air pollution, has been associated with adverse birth outcomes. Yet it remains unclear whether and how socioeconomic status (SES) affects gestational PAH exposure., Objective: To examine whether there are socioeconomic disparities in PAHs exposure among pregnant women from Rochester, NY, and if so, to what extent disproportionate proximity to air pollution sources, measured by residential distance to transportation-related sources, contributed to the exposure disparity., Methods: We measured 1-hydroxypyrene concentrations in 726 urine samples collected from 305 pregnant women up to three samples throughout pregnancy. Residential distances to transportation-related sources were calculated based on participants' home addresses. We used linear mixed-effects models with random intercepts of participants to examine associations between 1-hydroxypyrene, SES indicators, and distance to transportation-related sources. We used structural equation modelling to assess to what extent distance to transportation-related sources contributes to the socioeconomic disparity in 1-hydroxypyrene concentrations., Results: Reduced household income and maternal education level were both significant SES predictors of 1-hydroxypyrene concentrations, after the adjustment for other maternal demographic characteristics. Each interquartile range (IQR) increases in residential proximity to the airport (from 14.3 to 6.0 km), the railroad yard (from 22.3 to 6.0 km), and annual average daily traffic within 300 m (from 3796 to 99,933 vehicles/year) were associated with 15.0% (95%CI: 7.0-22.2%), 15.4% (95%CI: 6.5-23.5%), and 13.6% (95%CI: 4.7-23.3%) increases in 1-hydroxypyrene concentrations, respectively. Proximity to these sources jointly explained 10% (95%CI: 1.6-18.4%) of the 1-hydroxypyrene concentration change associated with decreases in SES as a latent variable defined by both household income and education level., Impact Statement: Our findings suggest that efforts to address disproportionate residential proximity to transportation-related sources may reduce the socioeconomic disparity in PAH exposure., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Historically, consumer acceptance of beef was determined by tenderness. Developments in genetics and management over the last couple of decades have improved tenderness to the point that it is secondary to other factors in beef's taste. Flavor, however, is an extraordinarily complex taste attribute dependent on biological sensors in the mouth, sinus cavity, and jaws. The culinary industry has recently focused on innovative ways to give consumers new products satisfying their curiosity about different foods, especially proteins. Competition from plant-based, cell-based, and even other animal-based proteins provides diversity in consumers' ability to select a protein that satisfies their desire to include unique products in their diet. Consequently, the beef industry has focused on flavor for the last 10 to 15 years to determine whether it can provide the guardrails for beef consumption in the future. The U.S. beef industry formed a Flavor Working Group in 2012 composed of the authors listed here to investigate new and innovative ways to manage and measure beef flavor. The results of this working group have resulted in dozens of papers, presentations, abstracts, and symposia. The objective of this manuscript is to summarize the research developed by this working group and by others worldwide that have investigated methodologies that measure beef flavor. This paper will describe the strengths of the research in beef flavor measurement and point out future needs that might be identified as technology advances., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Perfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function., Objectives: The objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes., Methods: Using data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image., Results: In both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (β = -0.23, 95% CI: -0.41, -0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (β = -0.19, 95% CI: -0.34, -0.051). There were no reliable differences in effect by fetal sex., Discussion: The findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Beef flavor continues to be one of the largest drivers of beef demand and a differentiation point of beef from other competing proteins. Tenderness has long been identified as the most important palatability trait for consumer satisfaction. However, as technological advancements and industry practices evolve and improve in response to tenderness management, flavor has emerged as a key driver of consumer satisfaction. In response, the beef industry has recently invested in research focused on beef flavor development, measurement, and management to better understand the factors impacting flavor and help beef maintain this advantage. The current review paper is the second of two such papers focused on summarizing the present knowledge and identifying knowledge gaps. While the other review focuses on current practices related to beef flavor measurement, this review will cover research findings related to beef flavor management. Numerous production and product management factors influence beef flavor. Pre-harvest factors including marbling level, animal genetics/cattle type, diet, and animal age, can influence beef flavor. Moreover, numerous post-harvest product management factors, including product type, aging length and conditions, cookery methods, product enhancement, muscle-specific factors, packaging, retail display factors, and antimicrobial interventions, have all been evaluated for their impact on beef flavor characteristics. Results from numerous studies evaluating many of these factors will be outlined within this review in order to present management and production chain factors that can influence beef flavor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The environmental toxicant cadmium (Cd) impairs the growth of rodents and humans in utero which in turn heightens susceptibility to diseases later in life. We previously demonstrated that the maternal-facing efflux transporter, breast cancer resistance protein (human BCRP/ABCG2, mouse Bcrp/Abcg2) confers resistance against Cd toxicity in human trophoblasts. In the current study, we sought to determine whether the absence of Bcrp alters the fetoplacental disposition and toxicity of Cd in mice. Pregnant female wild-type (WT) and Bcrp-null mice (n = 9-10/group) were administered a single injection of saline (5 ml/kg) or CdCl2 (5 mg/kg) on gestational day (GD) 9. Following Cd treatment, Bcrp-null offspring were shorter and accumulated more Cd in their placentas on GD 17 compared to WT mice. Because Cd can adversely impact placentation and transplacental nutrient delivery in mice, multiple pathways were assessed using morphometrics and immunohistochemistry including placenta zonation, vasculature development, and nutrient transporter expression. Most notably, the placentas of Bcrp-null mice had reduced immunostaining of the cell adhesion marker, β-catenin, and the trophoblast marker, cytokeratin, as well as decreased expression of divalent metal nutrient transporters (Dmt1, Zip14, and ZnT1) following Cd treatment. In summary, the absence of Bcrp expression increased placental concentrations of Cd which was associated with shorter fetal size that may be related to differential changes in molecular patterns of placental development and nutrition., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The impact of different cooking methods, degree of doneness, cuts, and marbling scores on beef juiciness and tenderness have been examined. However, relationships between tenderness and juiciness, the two major components of beef texture, for descriptive and consumer sensory data with Warner-Bratzler shear force (WBSF) and overall consumer liking have not been elucidated using US consumers recently. The objective was to use two data sets that measured consumer sensory and beef descriptive tenderness and juiciness attributes to understand relationships between consumer and trained descriptive tenderness and juiciness attributes, and Warner-Bratzler shear force (WBSF) and overall consumer liking. Data were analyzed in two sets, top loin steaks (n = 119) or beef cuts (n = 276) that included top loin steaks, tenderloin steaks, top sirloin steaks, and bottom round roasts. Average WBSF values for top loin steaks and beef cuts were 26.0 and 28.5 N, respectively. Consumer attributes were not strong predictors of WBSF. WBSF was more highly related to descriptive tenderness ratings (R 2  = 0.37 for beef cuts). Overall liking was correlated to consumer attributes, most strongly to flavor liking (R 2  = 0.94 for beef cuts). Descriptive and consumer juiciness ratings did not appreciably improve predictability of regression equations for either WBSF or consumer overall liking. These results indicated that using a WBSF value of 28 N or less for beef cuts would provide assurance for moderately tender beef as defined by descriptive sensory evaluation, and WBSF values between 30 and 32 N were slightly tender (as defined by descriptive sensory evaluation). Beef with WBSF values of 40 or higher were defined as slightly tough or tougher., Competing Interests: Declaration of Competing Interest We declare no conflict of interest associated with this publication and no financial support for this work that could have influenced the outcome. As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Thirty-three USDA Select boneless top loins were selected from carcasses at a commercial major packing plant, vacuum-packaged, and aged for 14 d (4 °C). The loins were then divided into 10 portions (5 grill temperatures for each of trained sensory panel and Warner-Bratzler shear force). Flat-top electric grills were pre-heated to 1 of 5 different temperatures: 149 °C (149), 177 °C (177), 204 °C (204), 232 °C (232), or 260 °C (260). Steaks were placed on the grill, turned when the internal temperature reached 35 °C and removed when the internal temperature reached 71 °C. A trained sensory panel evaluated ten basic flavors and five texture attributes. Extra cubes from each sample were frozen in liquid nitrogen and stored at -80 °C for GC/MS volatile aroma compound analysis. Beef identity, brown, and roasted flavor descriptors increased linearly (P < 0.001) while bloody/serumy tended to decrease (P = 0.016) and sour flavor decreased (P = 0.006) linearly as grill temperature increased. Furthermore, burnt (deviation P = 0.008) and bitter (deviation P = 0.012) flavor descriptors were affected by effects other than linear or quadratic, while umami (P = 0.002) and overall sweet (P = 0.016) flavors increased quadratically from 149 to 232 then declined at 260 grill temperatures. Two alcohols, eight aldehydes, four alkanes, three furans, eight ketones, and twelve pyrazines were impacted by differences the grill temperature. Increasing grill temperature increases volatile compounds, primarily from the Maillard reaction, that improve positive beef flavor descriptors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Neighborhood stressors (e.g., crime and deprivation) have been associated with adverse pregnancy outcomes including preterm birth and low birth weight. A potential mechanism is disruption of maternal endocrine pathways. While stress hormones (e.g., cortisol) have received much attention, other relevant hormones, including sex steroids, have been overlooked., Methods: Pregnant women in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaires, and medical record data (n = 262). In each trimester, maternal serum total testosterone [TT], estrone, estradiol, and estriol were measured using LC/MS-MS and serum free testosterone was measured by equilibrium dialysis. In the third trimester, participants reported on neighborhood stress over the last year through the validated City Stress Inventory. We examined two subscales: 11-item neighborhood disorder (e.g., vacant buildings, crime) and 7-item exposure to violence (personal experiences of violence). Composite scores were calculated and examined categorically (quartile (Q) for neighborhood disorder and any/none for exposure to violence). We fitted linear mixed models examining associations between neighborhood stressors and sex steroid hormones across pregnancy as well as trimester-specific linear regression models, all adjusting for confounders. Secondarily, we stratified by fetal sex. Results are presented as percentage change (∆%) and 95% confidence interval (CI) in hormones., Results: Most participants (73%) reported one or more exposures to neighborhood disorder; 22% reported any exposure to violence. In adjusted models, neighborhood disorder was associated with higher TT across pregnancy (Q2: %∆= 37.3, 95%CI: 13.2, 66.5; Q3: %∆= 22.2, 95%CI: 1.2, 47.5; and Q4: %∆= 25.7, 95%CI: 1.6, 55.3), with the strongest associations observed in the third trimester (Q2: %∆= 38.0, 95%CI: 10.6, 72.1; Q3: %∆= 29.2, 95%CI: 4.4, 59.9; and Q4: %∆=33.4, 95%CI: 4.9, 69.6). In stratified models, neighborhood disorder was associated with higher TT among women carrying male fetuses (%∆ range: 48.2-84.8). Exposure to violence was not associated with any hormones., Conclusion: Neighborhood disorder is associated with higher maternal testosterone levels, which may have implications for maternal and child health. Additional research is needed to understand the mechanisms by which neighborhood stress impacts endocrine physiology., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Consumer acceptance and overall liking has been shown to be related to beef instrumental and trained sensory attributes related to beef flavor, tenderness, and juiciness. Our objective was to understand the relationships between descriptive beef flavor and texture attributes, Warner-Bratzler shear force (WBSF), and consumer liking attributes for light US beef eaters. It is not known if light beef eaters have different drivers of overall liking. Treatments were created to differ in beef flavor and texture by utilizing different beef cuts (Choice top loin, high pH top loin, Select top sirloin, Choice tenderloin steaks, and Select and Choice bottom rounds roasts) cooked to 58 °C or 80 °C. Cooking methods included either a George Forman grill, food-service grill, or crock-pot. Cooking method, cut, and internal temperature impacted beef descriptive flavor and texture attributes, WBSF and consumer liking ratings (P ≤ 0.05) similarly. Descriptive juiciness and tenderness attributes were highly related to each other and with consumer juiciness and tenderness liking ratings. Consumer overall liking was closely related to descriptive fat-like, overall sweet, sweet and salty attributes. Musty/moldy, liver-like, and sour aromatic attributes were negatively associated with consumer liking. Overall flavor accounted for 85% of the variation in overall liking and tenderness liking contributed an additional 4%. While light beef eaters used different parts of the scale, they rated beef across treatments similarly. When beef flavor and texture descriptive attributes differed, consumer liking was impacted for light beef eaters., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Precursors to flavor are important to its development, yet little is known about the intrinsic products of metabolism that influence flavor. Our objective was to use untargeted metabolomics and volatile aroma compounds to predict expert and consumer sensory traits. USDA Select and upper 2/3 Choice beef strip loins were wet aged for 10 or 20 d and then cut into steaks, vacuum-packaged, and frozen. Steaks were cooked to 63 °C, 71 °C, or 80 °C end-point internal steak temperature. USDA Choice steaks had more intense beef flavor identity, brown, roasted, fat-like, salty, sweet, sour, umami, buttery, and overall sweet flavors compared to USDA Select steaks (P < 0.05). Steaks cooked to 80 °C had more intense beef identity, brown, roasted, and umami flavors than steaks cooked to a lower degree of doneness. Steaks cooked to either 63 °C or 71 °C had more intense bloody, metallic, and sour flavors and were juicier, more tender, and had less connective tissue than steaks cooked to a higher degree of doneness. Volatile aroma compounds increased (P < 0.05) in Choice steaks aged for 20 d, while cooking steaks to 80 increased aldehydes, ketones, and pyrazines. Raw steaks had 69 small-molecule metabolomic compounds shared across all four quality grade x aging combinations, and discriminant analysis correctly categorized (P < 0.05) these metabolites. Metabolites and volatiles can be used to predict (r 2  > 0.85) expert and consumer sensory panel descriptors and liking., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In utero exposure to the toxic metal cadmium (Cd) alters fetoplacental growth in rodents and has been inversely associated with birth weight and infant size in some birth cohorts. Moreover, studies suggest that Cd may have differential effects on growth and development according to offspring sex. The purpose of the current study was to evaluate changes in male and female fetoplacental development following a single injection of saline (5 ml/kg ip) or cadmium chloride (CdCl 2 , 2.5, 5 mg/kg, ip) on gestational day (GD) 9. By GD18, no changes in fetal or placental weights were observed after treatment with 2.5 mg/kg CdCl 2 . By comparison, the weight and length of male fetuses and their placentas were reduced following treatment with 5 mg/kg CdCl 2 whereas no change was observed in females. In addition, the area of maternal and fetal blood vessels as well as the expression of the glucose transporters, Glut1 and Glut3, and the endothelial marker, CD34, were reduced in the placentas of CdCl 2 -treated male offspring compared to females. Interestingly, the placentas of females accumulated 80% more Cd than males after CdCl 2 (5 mg/kg) administration. Female placentas also had higher concentrations of zinc and the zinc transporter Znt1 compared to males which may explain the limited changes in fetal growth observed following CdCl 2 treatment. Taken together, disruption of vasculature development and reduced expression of glucose transporters in the placenta provide potential mechanisms underlying reduced fetal growth in male offspring despite the greater accumulation of Cd in female placentas., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lauren Aleksunes reports financial support was provided by National Institute of Environmental Health Sciences. Danielle Kozlosky reports financial support was provided by National Institute of Environmental Health Sciences. Emily Barrett reports financial support was provided by National Institute of Environmental Health Sciences. Lauren Aleksunes reports financial support was provided by National Center for Advancing Translational Sciences., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Sex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes., Methods: Retrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels., Results: In adjusted models, first trimester total testosterone (β=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (β=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (β=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone., Conclusion: Early-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meng, Thornburg, Hoeger, Núñez, Kautz, Evans, Wang, Miller, Groth, O’Connor and Barrett.)

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals found in drinking water and consumer products, resulting in ubiquitous human exposure. PFAS have been linked to endocrine disruption and altered weight gain across the lifespan. A limited and inconsistent body of research suggests PFAS may impact gestational weight gain (GWG) and postpartum body mass index (BMI), which are important predictors of overall infant and maternal health, respectively., Methods: In the Understanding Pregnancy Signals and Infant Development (UPSIDE/UPSIDE-MOMs) study (n = 243; Rochester, NY), we examined second trimester serum PFAS (PFOS: perfluorooctanesulfonic acid, PFOA: perfluorooctanoic acid, PFNA: perfluorononanoic acid, PFHxS: perfluorohexanesulfonic acid, PFDA: perfluorodecanoic acid) in relation to GWG (kg, and weekly rate of gain) and in the postpartum, weight retention (PPWR (kg) and total body fat percentage (measured by bioelectrical impedance)). We fit multivariable linear regression models examining these outcomes in relation to log-transformed PFAS in the whole cohort as well as stratified by maternal pre-pregnancy BMI (< 25 vs. =  > 25 kg/m 2 ), adjusting for demographics and lifestyle factors. We used weighted quantile sum regression to find the combined influence of the 5 PFAS on GWG, PPWR, and body fat percentage., Results: PFOA and PFHxS were inversely associated with total GWG (PFOA: ß = -1.54 kg, 95%CI: -2.79, -0.30; rate ß = -0.05 kg/week, 95%CI: -0.09, -0.01; PFHxS: ß = -1.59 kg, 95%CI: -3.39, 0.21; rate ß = -0.05 kg/week, 95%CI: -0.11, 0.01) and PPWR at 6 and 12 months (PFOA 6 months: ß = -2.39 kg, 95%CI: -4.17, -0.61; 12 months: ß = -4.02 kg, 95%CI: -6.58, -1.46; PFHxS 6 months: ß = -2.94 kg, 95%CI: -5.52, -0.35; 12 months: ß = -5.13 kg, 95%CI: -8.34, -1.93). PFOA was additionally associated with lower body fat percentage at 6 and 12 months (ß = -1.75, 95%CI: -3.17, -0.32; ß = -1.64, 95%CI: -3.43, 0.16, respectively) with stronger associations observed in participants with higher pre-pregnancy BMI. The PFAS mixture was inversely associated with weight retention at 12 months (ß = -2.030, 95%CI: -3.486, -0.573) amongst all participants., Conclusion: PFAS, in particular PFOA and PFHxS, in pregnancy are associated with altered patterns of GWG and postpartum adiposity with potential implications for fetal development and long-term maternal cardiometabolic health., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Gadolinium (Gd), a toxic rare earth element, has been shown to dissociate from chelating agents and bioaccumulate within tissues, raising concerns about the possibility of their remobilization during pregnancy with subsequent free Gd exposures to developing fetuses. Gd chelates are among the most commonly used magnetic resonance imaging (MRI) contrast agents. This investigation was undertaken after the detection of elevated Gd (800-1000× higher than the usual rare earth element levels) in preliminary unpublished studies from the placentae of subjects in the NIH ECHO/UPSIDE Rochester Cohort Study and unpublished studies from placentae analyzed in formalin-fixed placental specimens from Surgical Pathology at the University of Rochester. Fifteen pregnancies with elevated Gd were studied (12 first pregnancies and 3 second pregnancies). Maternal bloods were collected from all three trimesters, maternal, and cord (fetal) bloods at delivery as well as placental tissue. Breastmilk was also collected from selected mothers. It was determined that Gd was present in maternal bloods from all three trimesters, and in cord bloods and breastmilk in both first and second pregnancies. These results emphasize the need to fully appreciate the implications of pre-pregnancy exposure to Gd chelates and its potential effects on maternal and fetal health., (© 2023 Wiley Periodicals LLC.)

During the early phases of embryonic development, the yolk sac serves as an initial placenta in many animal species. While in some, this role subsides around the end of active organogenesis, it continues to have important functions in rodents, alongside the chorio-allantoic placenta. The yolk sac is the initial site of hematopoiesis in many animal species including primates. Cells of epiblastic origin form blood islands that are the forerunners of hematopoietic cells and of the primitive endothelial cells that form the vitelline circulation. The yolk sac is also a major route of embryonic and fetal nutrition apparently as long as it functions. In mammals and especially rodents, macro and micronutrients are absorbed by active pinocytosis into the visceral yolk sac, degraded and the degradation products (i.e., amino acids) are then transferred to the embryo. Interference with the yolk sac function may directly reflect on embryonic growth and development, inducing congenital malformations or in extreme damage, causing embryonic and fetal death. In rodents, many agents were found to damage the yolk sac (i.e., anti-yolk sac antibodies or toxic substances interfering with yolk sac pinocytosis) subsequently affecting the embryo/fetus. Often, the damage to the yolk sac is transient while embryonic damage persists. In humans, decreased yolk sac diameter was associated with diabetic pregnancies and increased diameter was associated with pregnancy loss. In addition, culture of rat yolk sacs in serum obtained from pregnant diabetic women or from women with autoimmune diseases induced severe damage to the visceral yolk sac epithelium and embryonic malformations. It can be concluded that as a result of the crucial role of the yolk sac in the well-being of the early embryo, any damage to its normal function may severely and irreversibly affect further development of the embryo/fetus., (© 2023 Wiley Periodicals LLC.)