fetal growth

胎儿生长
  • 文章类型: Journal Article
    目的:新生儿的长度呈现季节性波动,但是这些波动的模式差异很大。这项研究分析了1984年至2021年奥地利新生儿出生队列中出生月份的出生长度波动和时间变化。
    方法:这项以人口为基础的回顾性队列研究包括奥地利1984年至2021年期间的2317927例单足月新生儿。严格的纳入标准是母亲的奥地利国籍。出生月(MOB)对出生长度的影响是使用多变量线性模型对母亲的教育水平进行调整来估计的。新生儿性别,胎龄,新生儿的出生年份(YOB),和母亲的平等。
    结果:新生儿身长因MOB而异,但也有一个时间趋势。在截至2004年的出生队列中,最长的新生儿出生在2月,而从2008年起,最长的出生长度在夏季。
    结论:在这个以奥地利人口为基础的样本中,出生长度显示出生月份的非随机波动。这些模式,然而,随着时间的推移变化很大。
    OBJECTIVE: The length of newborns shows seasonal fluctuations, but the patterns of these fluctuations vary greatly. This study analyses the fluctuation in birth length by birth month and temporal changes in Austrian newborns from the 1984 to 2021 birth cohorts.
    METHODS: A total of 2 317 927 singleton-term births between 1984 and 2021 in Austria were included in this retrospective population-based cohort study. A strict inclusion criterion was the Austrian citizenship of the mother. The effect of month of birth (MOB) on birth length was estimated using a multivariable linear model adjusting for maternal educational level, newborn sex, gestational age, year of birth (YOB) of the newborn, and parity of the mother.
    RESULTS: Newborn length varied by MOB, but there was also a temporal trend. In the birth cohorts up to 2004, the longest newborns were born in February, while from 2008 onward, the longest birth lengths were observed in the summer months.
    CONCLUSIONS: In this Austrian population-based sample, birth length shows nonrandom fluctuations by birth month. These patterns, however, varied considerably over time.
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  • 文章类型: Journal Article
    背景/目标:剪切波弹性成像(SWE)作为超声生物测量和多普勒测速检查的辅助手段,用于检查胎盘功能障碍和次优胎儿生长尚不清楚。迄今为止,胎盘的力学特性与胎儿生长相关的数据有限。本研究旨在探讨胎盘剪切波速度(SWV)与超声估测胎儿体重(EFW)的关系,并确定胎盘SWV是否是胎龄较小(SGA)妊娠监测中胎盘功能的合适替代指标。方法:本前瞻性,观察性队列研究比较了SGA和适合胎龄(AGA)妊娠之间胎盘SWV的差异.在研究队列中,有221名单胎妊娠妇女-136(61.5%)AGA和85(38.5%)SGA。胎儿生物测定,多普勒测速仪,羊水最深的垂直口袋,从招募到出生,以2-4周的间隔测量平均SWV。结果:与AGA妊娠相比,SGA妊娠的平均胎盘SWV没有差异,与EFW也没有任何关系。结论:尽管其他研究表明胎盘硬度增加与SGA妊娠之间存在一定的相关性,我们的调查不支持这一点。SGA妊娠中胎盘组织的机械特性不会导致明显不同于AGA对照的胎盘SWV。由于这项研究没有区分体质或病理上的小胎儿,生长受限队列的进一步研究将是有益的.
    Background/Objectives: The utility of shear wave elastography (SWE) as an adjunct to ultrasound biometry and Doppler velocimetry for the examination of placental dysfunction and suboptimal fetal growth is unclear. To date, limited data exist correlating the mechanical properties of placentae with fetal growth. This study aimed to investigate the relationship between placental shear wave velocity (SWV) and ultrasound estimated fetal weight (EFW), and to ascertain if placental SWV is a suitable proxy measure of placental function in the surveillance of small-for-gestational-age (SGA) pregnancies. Methods: This prospective, observational cohort study compared the difference in placental SWV between SGA and appropriate-for-gestational-age (AGA) pregnancies. There were 221 women with singleton pregnancies in the study cohort-136 (61.5%) AGA and 85 (38.5%) SGA. Fetal biometry, Doppler velocimetry, the deepest vertical pocket of amniotic fluid, and mean SWV were measured at 2-4-weekly intervals from recruitment to birth. Results: There was no difference in mean placental SWV in SGA pregnancies compared to AGA pregnancies, nor was there any relationship to EFW. Conclusions: Although other studies have shown some correlation between increased placental stiffness and SGA pregnancies, our investigation did not support this. The mechanical properties of placental tissue in SGA pregnancies do not result in placental SWVs that are apparently different from those of AGA controls. As this study did not differentiate between constitutionally or pathologically small fetuses, further studies in growth-restricted cohorts would be of benefit.
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  • 文章类型: Journal Article
    尽管劳动力依赖于太多的相互作用因素,没有一个参数可以完全预测其结果,胎儿脑多普勒已经成为最可靠的预测工具,与胎儿体重相比,在怀孕的最后几周表现明显更差。脑多普勒的重要性遵循胎儿体重在妊娠最后几周增加其表现并在分娩前达到最高能力的反向途径。脑血流的组合,胎儿体重,选择的临床信息可以获得对分娩结果的适度预测,前提是劳动的间隔时间不长。
    Despite the fact that labor depends on too many interacting factors and no parameter can fully predict its outcome, fetal cerebral Doppler has emerged as the most reliable tool for prediction, in contrast with fetal weight, which performs significantly worse in the last weeks of pregnancy. The importance of the cerebral Doppler follows the inverse pathway of fetal weight increasing its performance in the last weeks of pregnancy and reaching its highest ability prior to labor. A combination of cerebral flow, fetal weight, and selected clinical information may obtain moderate predictions of labor outcome, provided the interval to labor is not long.
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  • 文章类型: Journal Article
    目前尚不清楚母亲接触生物质燃料是否以及如何影响婴儿出生时的人体测量学或身体比例,这与他们的生存有关,身体生长,和神经发育。因此,本研究旨在探讨家庭水平的生物质烹饪燃料暴露与孟加拉国农村女性出生时婴儿体型和身体比例之间的关系.共有909名妇女来自妊娠增重研究,这是在Matlab中进行的,孟加拉国的一个农村地区。婴儿体重(g),长度(cm),头围(cm),小于胎龄(SGAW),胎龄短(SGAL),低头围胎龄(SGAHC),黄体指数,和出生时的头化指数是研究的结果。在女性中,721(79.3%)依赖生物质燃料。与使用燃气做饭的母亲所生的婴儿相比,生物量使用者出生的人体重较低(β-94.3,CI-155.9,-32.6),长度(β-0.36,95%CI-0.68,-0.04),出生时头围(β-0.24,CI-0.47,-0.02)和较高的头化指数(β0.03,CI0.01,0.05)。母体生物量暴露更有可能导致对称SGA,尽管有证据表明有一些节省大脑的作用。
    It remains unclear whether and how maternal exposure to biomass fuel influences infant anthropometry or body proportionality at birth, which are linked to their survival, physical growth, and neurodevelopment. Therefore, this study seeks to explore the association between household-level exposure to biomass cooking fuels and infant size and body proportionality at birth among women in rural Bangladesh. A total of 909 women were derived from the Pregnancy Weight Gain study, which was conducted in Matlab, a rural area of Bangladesh. Infant\'s weight (g), length (cm), head circumference (cm), small for gestational age (SGAW), short for gestational age (SGAL), low head circumference for gestational age (SGAHC), ponderal index, and cephalization index at birth were the outcomes studied. Of the women, 721 (79.3%) were dependent on biomass fuel. Compared to infants born to mothers who used gas for cooking, those born to biomass users had lower weight (β - 94.3, CI - 155.9, - 32.6), length (β - 0.36, 95% CI - 0.68, - 0.04), head circumference (β - 0.24, CI - 0.47, - 0.02) and higher cephalization index (β 0.03, CI 0.01, 0.05) at birth. Maternal biomass exposure is more likely to lead to symmetric SGA, although there is evidence for some brain-sparing effects.
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  • 文章类型: Journal Article
    背景:慢性胎盘炎症是一组常规诊断的胎盘病变,反映了母亲的免疫功能障碍,胎儿,或者两者兼而有之。
    方法:2010年1月至2016年8月,在纽约长老会-布鲁克林卫理公会医院对所有足月分娩进行了完整的胎盘病理学检查。除了胎龄外,诊断是盲目的。CPI病变标记为慢性绒毛膜蜕皮炎,蜕膜浆细胞,基底板的慢性炎症与锚定绒毛炎,和慢性绒毛炎。
    结果:在足月妊娠队列中,257名(11.6%)男性和218名(9.8%)女性有≥1个CPI病变。慢性绒毛炎是最常见的(319或14%),患有慢性绒毛膜蜕膜炎,蜕膜浆细胞,94例(4%)基底板慢性炎症伴锚定绒毛炎,69(3%)和170(8%),分别。在男性中,慢性绒毛炎与较低的妊娠调整出生体重相关,与胎盘重量无关.在女性中,慢性绒毛炎与较低的妊娠调整出生体重有关,但在调整胎盘重量后效果变得不显著。
    结论:总之,CPI病变的发生率和与出生体重的关系因性别而异。慢性绒毛膜炎与女性出生体重较低有关;这种作用完全由胎盘重量介导。慢性绒毛炎在男性中表现出与慢性绒毛炎的微弱直接关联,但与男性胎盘重量较低无关。我们建议我们的结果与以前的出版物之间的差异反映了抽样偏差的影响。
    BACKGROUND: 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.
    CONCLUSIONS: 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.
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  • 文章类型: Journal Article
    目的:探讨孕妇总体力活动水平与中、剧烈运动与胎儿生长障碍之间的关系。
    方法:我们分析了参加中国医科大学纵向出生队列研究的2062对母儿。使用妊娠体力活动问卷评估三个月期间妇女的体力活动水平。较高水平的总体力活动被定义为达到或超过队列特定的第75百分位数,根据美国人的身体活动指南定义了更高水平的运动。胎儿生长障碍定义为出生时小于胎龄(SGA)或大于胎龄(LGA)。
    结果:本研究纳入的新生儿中,7.1%为SGA,15.5%为LGA。妊娠早期总体力活动水平较高(调整后相对风险(aRR),0.62(95%CI,0.42-0.91))和孕中期(aRR,0.62(95%CI,0.41-0.95))与SGA风险较低相关,在妊娠晚期,较高的总体力活动水平与较低的LGA风险相关(aRR,0.73(95%CI,0.54-0.97))。按亚型分析体力活动时,在孕早期和中期,较高水平的职业体力活动与SGA风险呈负相关,妊娠早期较高水平的职业性和低强度体力活动与LGA风险呈负相关。母亲遵守美国人身体活动指南与胎儿生长障碍的风险之间没有显着关联。
    结论:孕早期和中期较高的总体力活动水平与SGA风险降低相关,而妊娠晚期较高的总体力活动水平与LGA风险降低相关。应建议孕妇增加其总身体活动水平,而不是只专注于进行中等至剧烈运动。©2024国际妇产科超声学会。
    OBJECTIVE: To investigate the trimester-specific associations between maternal total physical activity level vs moderate-to-vigorous exercise and fetal growth disorders.
    METHODS: We analyzed 2062 mother-neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort-specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small-for-gestational age (SGA) or large-for-gestational age (LGA) at birth.
    RESULTS: Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42-0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41-0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54-0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low-intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders.
    CONCLUSIONS: A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate-to-vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
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  • 文章类型: Journal Article
    背景:2型糖尿病(T2D)的母体遗传风险与胎儿生长有关,但是遗传祖先的影响还没有完全理解。我们旨在研究遗传距离(GD)和遗传血统比例(GAP)对T2D的母体遗传风险评分(GRST2D)与胎儿体重和出生体重的相关性的影响。
    方法:来自NICHD胎儿生长研究的多祖先孕妇(n=1,837)——单胎队列被纳入当前分析。胎儿体重(以克计,g)是根据胎儿生物测定的超声测量结果估计的,分娩时测量出生体重(g)。使用最新的跨祖先全基因组关联研究中鉴定的T2D相关变体计算GRST2D,并将其分类为四分位数。使用四个参考人群的基因型数据估计GD和GAP。GD被归类为最接近的,中间,和最远的三元,GAP被归类为最高,中等,和最低。进行线性回归分析以测试GRST2D与胎儿体重和出生体重的关联。对协变量进行调整,在每个GD和GAP类别中。
    结果:在来自非洲和美洲土著祖先的GD最接近的女性中,与第一个四分位数相比,第四个和第三个GRST2D四分位数与5.18至7.48g(17-20周)和6.83至25.44g(19-27周)的胎儿体重显着相关,分别。在来自欧洲血统的中GD女性中,第4个GRST2D四分位数与5.73~21.21g(18~26周)更大的胎儿体重显著相关.此外,在来自欧洲和非洲祖先的中间GD的女性中,与第一个四分位数相比,第四个和第二个GRST2D四分位数与117.04g(95%CI=23.88-210.20,p=0.014)和95.05g(95%CI=4.73-185.36,p=0.039)更大的出生体重显着相关,分别。与东亚血统最接近GD的女性之间没有显着关联,而与东亚GAP最高的女性之间存在正显著关联。
    结论:母体GRST2D与胎儿生长之间的关联始于孕中期早期,并受GD和GAP的影响。结果表明,遗传GD和GAP的使用可以提高GRS的普适性。
    BACKGROUND: Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry is not yet fully understood. We aimed to investigate the influence of genetic distance (GD) and genetic ancestry proportion (GAP) on the association of maternal genetic risk score of T2D (GRST2D) with fetal weight and birthweight.
    METHODS: Multi-ancestral pregnant women (n = 1,837) from the NICHD Fetal Growth Studies - Singletons cohort were included in the current analyses. Fetal weight (in grams, g) was estimated from ultrasound measurements of fetal biometry, and birthweight (g) was measured at delivery. GRST2D was calculated using T2D-associated variants identified in the latest trans-ancestral genome-wide association study and was categorized into quartiles. GD and GAP were estimated using genotype data of four reference populations. GD was categorized into closest, middle, and farthest tertiles, and GAP was categorized as highest, medium, and lowest. Linear regression analyses were performed to test the association of GRST2D with fetal weight and birthweight, adjusted for covariates, in each GD and GAP category.
    RESULTS: Among women with the closest GD from African and Amerindigenous ancestries, the fourth and third GRST2D quartile was significantly associated with 5.18 to 7.48 g (weeks 17-20) and 6.83 to 25.44 g (weeks 19-27) larger fetal weight compared to the first quartile, respectively. Among women with middle GD from European ancestry, the fourth GRST2D quartile was significantly associated with 5.73 to 21.21 g (weeks 18-26) larger fetal weight. Furthermore, among women with middle GD from European and African ancestries, the fourth and second GRST2D quartiles were significantly associated with 117.04 g (95% CI = 23.88-210.20, p = 0.014) and 95.05 g (95% CI = 4.73-185.36, p = 0.039) larger birthweight compared to the first quartile, respectively. The absence of significant association among women with the closest GD from East Asian ancestry was complemented by a positive significant association among women with the highest East Asian GAP.
    CONCLUSIONS: The association between maternal GRST2D and fetal growth began in early-second trimester and was influenced by GD and GAP. The results suggest the use of genetic GD and GAP could improve the generalizability of GRS.
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  • 文章类型: Journal Article
    背景:已经广泛研究了妊娠中晚期母亲抑郁对胎儿生长的影响。然而,孕早期产妇抑郁与胎儿宫内发育之间的关联尚不清楚.
    方法:一项前瞻性研究包括23,465名符合条件的孕妇及其后代在上海一家医院中心进行。在14孕周之前使用患者健康问卷(PHQ-9)评估产前抑郁症。使用带有分数多项式的多水平模型比较了三个时期(16-23、24-31和32-41孕周)不同母体抑郁状态的胎儿生长轨迹的差异。
    结果:妊娠早期有抑郁症状的女性有更高的纵向胎儿轨迹,胎儿体重估计增加(β=0.33;95%CI,0.06-0.61),与没有抑郁症状的人相比。在23孕周之前观察到有抑郁症状的妇女的胎儿腹围增加。患有早孕抑郁症的母亲所生的后代出生体重明显较高,为14.13g(95%CI,1.33-27.81g),胎龄严重大尺寸的风险增加(调整后比值比[aOR],1.64;95%CI,1.32-2.04)和巨大儿(aOR,1.21;95%CI,1.02-1.43)。
    结论:自评量表用于评估抑郁症状,而不是临床诊断。并且没有探讨早期妊娠抑郁症对后代的长期影响。
    结论:该研究揭示了妊娠早期母亲抑郁与胎儿生物特征增加之间的关联。出生体重较高,以及胎龄和巨大儿严重增大的风险。
    BACKGROUND: The impacts of maternal depression during mid-to-late pregnancy on fetal growth have been extensively investigated. However, the association between maternal depression during early pregnancy and fetal intrauterine growth are less clear.
    METHODS: A prospective study comprised 23,465 eligible pregnant women and their offspring was conducted at a hospital-based center in Shanghai. Prenatal depression was assessed used using Patient Health Questionnaire (PHQ-9) before 14 gestational weeks. Differences in fetal growth trajectory of different maternal depressive statuses during three periods (16-23, 24-31, and 32-41 gestational weeks) were compared using a multilevel model with fractional polynomials.
    RESULTS: Women with depressive symptoms during early pregnancy had higher longitudinal fetal trajectories, with an estimated increase in fetal weight (β = 0.33; 95 % CI, 0.06-0.61), compared to those without depressive symptoms. Increases in fetal abdominal circumference among women with depressive symptoms were observed before 23 gestational weeks. Offspring born to mothers with early pregnancy depression had a significantly higher birth weight of 14.13 g (95 % CI, 1.33-27.81 g) and an increased risk of severe large size for gestational age (adjusted odds ratio [aOR], 1.64; 95 % CI, 1.32-2.04) and macrosomia (aOR, 1.21; 95 % CI, 1.02-1.43).
    CONCLUSIONS: Self-rated scale was used to assess depressive symptoms rather than clinical diagnosis. And Long-term effects of early pregnancy depression on offspring were not explored.
    CONCLUSIONS: The study revealed an association between maternal depression during early pregnancy and increased fetal biometrics, higher birth weight, and an elevated risk of severe large size for gestational age and macrosomia.
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  • 文章类型: Journal Article
    背景:近年来,受益于临床技术的不断改进和生育能力保存的优势,胚胎冷冻保存的应用在世界范围内迅速发展。然而,在这种增长中,对其安全的担忧依然存在。许多研究强调了与冷冻胚胎移植(FET)相关的围产期并发症的风险增加。如孕龄大(LGA)和妊娠期高血压疾病。因此,探讨胚胎冷冻保存的潜在风险及其相关机制势在必行。
    方法:鉴于临床样本受到严格的伦理约束,我们在这项研究中采用了小鼠模型.建立了三个实验组:自然受孕(NC)组,新鲜胚胎移植(Fresh-ET)组,和FET组。在胚胎冷冻保存后计算囊胚形成率和着床率。根据胎儿和胎盘重量评估FET对胎儿生长的影响。进行胎盘RNA-seq,包括各种比较的综合分析(Fresh-ET与NC,FETvs.NC,和FETvs.新鲜ET)。
    结果:胚胎冷冻保存后观察到胚泡形成和着床率降低。与NC组相比,Fresh-ET导致胎儿体重显着下降,而FET扭转了这种下降。RNA-seq分析表明,FET中的大多数表达变化是遗传自Fresh-ET,仅归因于胚胎冷冻保存的改变是中等的。出乎意料的是,某些显示Fresh-ET改变的基因倾向于在FET中恢复。进一步的分析表明,这种消退可能是FET中胎儿生长受限改善的基础。在FET和Fresh-ET组中印迹基因的表达均被破坏。
    结论:根据我们对小鼠模型的实验数据,胚胎冷冻保存的影响不如新鲜ET中的其他体外操作明显。然而,胚胎发育潜能的损害和胎盘中的基因改变仍然表明这是一个有风险的手术。
    BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.
    METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).
    RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.
    CONCLUSIONS: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.
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  • 文章类型: Journal Article
    背景:有机磷酸酯(OPEs)暴露可能会影响后代健康。然而,潜在的机制没有得到很好的记录。
    目的:基于出生队列研究,我们的目的是调查妊娠OPEs暴露之间的关联,过氧化物酶体增殖物激活受体(PPAR)信号通路相关基因的胎盘DNA甲基化水平,和胎儿的生长。
    方法:我们测量了733对母子对的母体尿液样本中8种OPE代谢物的浓度和新生儿人体测量。在327个胎盘样本中,我们评估了参与PPARs信号通路并在胎盘中表达的14个基因的DNA甲基化水平.多元线性回归模型用于检查OPEs暴露与胎盘DNA甲基化的相关性。新生儿人体测量法测量OPEs和胎盘DNA甲基化。进行了因果介导分析,以检查胎盘DNA甲基化在OPEs暴露与胎儿生长之间的途径中的潜在介导作用。
    结果:我们观察到OPEs暴露的一般模式与候选基因的超甲基化有关,在几个OPEs与RXRA的统计上显着的关联中,ACAA1、ACADL、ACADM,PLTP,和NR1H3甲基化。Further,妊娠暴露于BCIPP,DPP,BBOEP,∑NCl-OPEs,和∑OPEs倾向于与较低的人体测量值相关,在臂围上观察到更显著的关联,腹部和背部皮褶厚度。值得注意的是,RXRA,ACAA1,ACOX1,CPT2,ACADM,和NR1H3甲基化倾向于与较低的新生儿人体测量相关,尤其是腹部和背部皮褶厚度。此外,调解分析表明,DPP对背部皮褶厚度的总影响的19.42%是由RXRA甲基化的变化介导的,RXRA甲基化有显著的间接作用。
    结论:妊娠OPEs暴露可破坏PPARAR信号通路相关基因的胎盘DNA甲基化水平,这可能有助于OPEs对胎儿生长的影响。
    BACKGROUND: Organophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented.
    OBJECTIVE: Based on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth.
    METHODS: We measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth.
    RESULTS: We observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation.
    CONCLUSIONS: Gestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth.
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