Air pollution exposure and its health effects are a central concern of environmental epigenetic research with birth cohorts. This article explores why researchers have turned to the placenta as a research object to study the dynamic interactions between in utero exposure to air pollution and future child health. Drawing on Science and Technology Studies, particularly the bio-object concept, this article analyses the transformation of the placenta into a technologically manipulated postgenomic bio-object through scientific discourse and practice. Building on ethnographic fieldwork conducted at an institute of epidemiology and public health in Spain, we analyse how researchers deal with the tension between the placenta’s promises for epigenetic research and the practical research realities in postgenomic sciences. First, researchers discursively call upon the placenta as a suitable research object that embodies air pollution exposure and becomes entangled with and responds to this exposure via epigenetic changes. Studying the placenta promises to elucidate the temporally dynamic and environmentally embedded process of disease development as one of postgenomics’ core epistemic concerns. Second, in practice, however, accessing and preparing the postpartum placenta for epigenetic analysis defies its promise as a postgenomic bio-object. The constraints of research with birth cohorts, such as only having access to the postpartum placenta at birth, limit what researchers can know about the dynamic process of disease development. Third, we show how researchers deal with these limitations by assembling additional data in and around this organ to recontextualise the epigenetic analysis performed in the postpartum placenta and revive its postgenomic character. We conclude by discussing how ethnographies of epistemic practices provide entry points to collaboratively reflect upon the theoretical and methodological opportunities and challenges in birth cohort research to study biosocial dynamics. We suggest avenues for using qualitative social science perspectives for future biosocial research and collaboration between the social and life sciences.

The extent of de-novo biosynthesis of non-essential fatty acids (FA) and the endogenous biosynthesis of long chain PUFA in human fetuses remain largely unknown. We used natural variations in the 13C:12C (δ 13C) of plasma phospholipids of the woman at delivery and of cord blood to infer fetal biosynthesis of FA. We studied thirty-nine mother–fetus pairs with uncomplicated pregnancies and term delivery. Eighteen women were supplemented with DHA, from pregnancy week 20 until delivery, sourced from an algae (n 13) or fish oil (n 5), each with slightly different 13C content. Twenty-one women did not receive DHA supplementation. We measured the δ 13C value of selected phospholipid FA (C16:0, C18:0, C18:1n-9, C18:2n-6, C20:4n-6 and C22:6n-3) in maternal and cord plasma samples at delivery using isotope ratio MS. We found significant linear correlations for δ 13C values of FA between mothers and their fetuses (C16:0, r = 0·8535; C18:0, r = 0·9099; C18:1n-9, r = 0·8079; C18:2n-6, r = 0·9466; C20:4n-6, r = 0·9257 and C22:6n-3, r = 0·9706). Women supplemented with algal DHA had significantly lower DHA δ 13C values in their plasma phospholipids than those supplemented with fish DHA or those who did not receive DHA supplementation (P < 0·001). There was no significant difference in δ 13C values of FA between women at delivery and their fetuses. These findings strongly suggest that the human fetus is highly dependent on the placental transport of maternal plasma FA, particularly DHA. The limited fetal biosynthesis of major FA emphasises the crucial role of maternal nutrition and placental well-being in fetal development.

Iodine and thyroid hormones (TH) transport in the placenta are essential for fetal growth and development, but there is little research focus on the human placenta. The research aimed to investigate iodine and TH transport mechanisms in the human placenta. The placenta was collected from sixty healthy pregnant women. Urinary iodine concentration (UIC), serum iodine concentration (SIC), placenta iodine storage (PIS) and the concentration of serum and placenta TH were examined. Five pregnant women were selected as insufficient intake (II), adequate intake (AI) and above requirements intake (ARI) groups. Localisation/expression of placental sodium/iodide symporter (NIS) and Pendrin were also studied. Results showed that PIS positively correlated with the UIC (R = 0·58, P < 0·001) and SIC (R = 0·55, P < 0·001), and PIS was higher in the ARI group than that in the AI group (P = 0·017). NIS in the ARI group was higher than that in the AI group on the maternal side of the placenta (P < 0·05). NIS in the II group was higher than that in the AI group on the fetal side (P < 0·05). In the II group, NIS on the fetal side was higher than on the maternal side (P < 0·05). Pendrin was higher in the II group than in the AI group on the maternal side (P < 0·05). Free triiodothyronine (r = 0·44, P = 0·0067) and thyroid-stimulating hormone (r = 0·75, P < 0·001) between maternal and fetal side is positively correlated. This study suggests that maternal iodine intake changes the expression of NIS and Pendrin, thereby affecting PIS. Serum TH levels were not correlated with placental TH levels.

Fetal growth restriction (FGR) is associated with increased risk of developing non-communicable diseases. We have a placenta-specific nanoparticle gene therapy protocol that increases placental expression of human insulin-like growth factor 1 (hIGF1), for the treatment of FGR in utero. We aimed to characterize the effects of FGR on hepatic gluconeogenesis pathways during early stages of FGR establishment, and determine whether placental nanoparticle-mediated hIGF1 therapy treatment could resolve differences in the FGR fetus. Female Hartley guinea pigs (dams) were fed either a Control or Maternal Nutrient Restriction (MNR) diet using established protocols. At GD30-33, dams underwent ultrasound guided, transcutaneous, intraplacental injection of hIGF1 nanoparticle or PBS (sham) and were sacrificed 5 days post-injection. Fetal liver tissue was fixed and snap frozen for morphology and gene expression analysis. In female and male fetuses, liver weight as a percentage of body weight was reduced by MNR, and not changed with hIGF1 nanoparticle treatment. In female fetal livers, expression of hypoxia inducible factor 1 (Hif1α) and tumor necrosis factor (Tnfα) were increased in MNR compared to Control, but reduced in MNR + hIGF1 compared to MNR. In male fetal liver, MNR increased expression of Igf1 and decreased expression of Igf2 compared to Control. Igf1 and Igf2 expression was restored to Control levels in the MNR + hIGF1 group. This data provides further insight into the sex-specific mechanistic adaptations seen in FGR fetuses and demonstrates that disruption to fetal developmental mechanisms may be returned to normal by treatment of the placenta.

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.

Correct placental development and function are critical to both the mother's and the foetus' health during pregnancy. Placental function depends on the correct development of the vascular network, which requires proper angiogenesis. Impaired angiogenesis in the placenta can induce foetal growth restriction, preeclampsia, and even foetal death. Placental angiogenesis is finely controlled by ubiquitous and pregnancy-specific angiogenic factors. Jumonji domain-containing protein 6 (JMJD6) is a Fe (II)- and 2-oxoglutarate (2OG)-dependent oxygenase that catalyses arginine demethylation and lysine hydroxylation of histone and non-histone peptides. JMJD6 has been implicated in embryonic development, cellular proliferation and migration, self-tolerance induction in the thymus, and adipocyte differentiation. In this review we present JMJD6's structure and activity, as well as its role in angiogenesis, oxygen sensing, and adverse pregnancy outcomes related to placental development. Understanding the interaction between JMJD6 and other placental factors may identify potential therapeutic targets for correcting abnormal placental angiogenesis and function.

In the United States, cardiovascular disease is the leading cause of death and the rate of maternal mortality remains among the highest of any industrialized nation. Maternal cardiometabolic health throughout gestation and postpartum is representative of placental health and physiology. Both proper placental functionality and placental microRNA expression are essential to successful pregnancy outcomes, and both are highly sensitive to genetic and environmental sources of variation. Placental pathologies, such as preeclampsia, are associated with maternal cardiovascular health but may also contribute to the developmental programming of chronic disease in offspring. However, the role of more subtle alterations to placental function and microRNA expression in this developmental programming remains poorly understood. We performed small RNA sequencing to investigate microRNA in placentae from the Rhode Island Child Health Study (n = 230). MicroRNA counts were modeled on maternal family history of cardiovascular disease using negative binomial generalized linear models. MicroRNAs were considered to be differentially expressed at a false discovery rate (FDR) less than 0.10. Parallel mRNA sequencing data and bioinformatic target prediction software were then used to identify potential mRNA targets of differentially expressed microRNAs. Nine differentially expressed microRNAs were identified (FDR < 0.1). Bioinformatic target prediction revealed 66 potential mRNA targets of these microRNAs, many of which are implicated in TGFβ signaling pathway but also in pathways involving cellular metabolism and immunomodulation. A robust association exists between familial cardiovascular disease and placental microRNA expression which may be implicated in both placental insufficiencies and the developmental programming of chronic disease.

Males and females have been proposed to have different prenatal growth strategies, whereby males invest more in fetal growth and less in placental development, leaving them more susceptible to early-life adversity. We tested predictions of this hypothesis using data from the National Collaborative Perinatal Project. Male newborns were heavier than females, but there was no difference in placental weight, adjusting for birthweight. Among infants born prior to 33 weeks, the difference in birthweight between males and females was greater among those who did not survive than among those who did, potentially reflecting a strategy whereby males maintained growth in the face of prenatal insults, while females adjusted growth. However, there was no significant difference in mortality between the sexes. Being born small-for-gestational age or very preterm (prior to 33 weeks) was associated with significantly reduced performance for most of the cognitive traits examined at 7 years, although maternal preeclampsia was associated with reduced performance in fewer traits. Generally, these effects of early-life adversity (poor fetal growth, prematurity, and preeclampsia) did not differ between the sexes. However, analyzing the sexes separately (rather than testing the interaction between sex and adversity) resulted in numerous spurious sex-specific effects, whereby the effect of early-life adversity appeared to be significant in one sex but not the other. Overall, we found little support for the hypothesis that males prioritize growth more than females, and that this makes them more susceptible to early-life adversity. Furthermore, our results show that analyzing the sexes separately, rather than testing the adversity by sex interaction, can be highly misleading.

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.

Globally, the availability and formulations for the administration of cannabis are changing with decriminalization or legalization of recreational use in some jurisdictions, and the prescription of cannabis also occurring. These changes are likely to affect the prevalence of use, including by women of childbearing age. The effects of in utero and infant alcohol and tobacco exposure are well-documented, but the outcomes of cannabis exposure are less certain. The content of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis has progressively increased over several decades. This review explores the limited knowledge surrounding the epidemiology of gestational and postnatal cannabis exposure and implications for the mother–placenta–fetus/neonate triad. We examine cannabis’ effects from antenatal and lactation exposure on (a) pregnancy and perinatal outcomes, (b) placental health, and (c) longer term cardiometabolic and neurodevelopmental risks and outcomes. Though definitive outcomes are lacking, gestational cannabis has been associated with increased risk of other substance use during pregnancy; impaired placental blood flow; increased risk of small for gestational age births; and associated complications. Childhood and adolescent outcomes are sparsely assessed, with suggested outcomes including increased risk of depression and attention-deficit hyperactivity disorder. Cardiometabolic implications of gestational cannabis use may include maternal fatty liver, obesity, insulin resistance, and increased risk of gestational diabetes mellitus (GDM), with potential consequences for the fetus. Clinical implications for pediatric practice were explored in a bid to understand any potential risk or impact on child health and development.

Chronic fatigue syndrome (CFS) is characterized by extreme fatigue and disabling symptoms. Women with CFS often have a high risk of gynaecological problems such as irregular menstruation, endometriosis and pelvic pain and sexual dysfunction. Our previous results have shown that, in pregnant mice, CFS significantly decreased the progestational hormone level in serum, as well as learning and memory, and the function of the hypothalamus–pituitary–gonadal axis. In addition, the F1 generation also suffered from congenital hypothyroidism. At present, there has been no report about placenta formation and embryonic development in pregnant mice with CFS. The aim of the present study was to investigate the influence of CFS on the morphology, oxidative stress and Wnt/β-catenin signalling pathway during placenta formation. In this study, we found that CFS decreased the number of implantation sites for blastocysts, and increased the number of absorbed, stillborn and malformed fetuses. The morphology and structure of the placenta were abnormal in pregnant mice with CFS. Further study found that the oxidative stress in serum, uterus and placenta was increased in pregnant mice with CFS, while the levels of antioxidase were decreased. CFS also inhibited the Wnt/β-catenin signalling pathway in the placenta. These results suggested that inhibition of the Wnt/β-catenin signalling pathway and enhanced oxidative stress play an important role in abnormal placentation in pregnant mice with CFS.

To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows’ diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1–PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.

Optimal placental function is critical for fetal development, and therefore a crucial consideration for understanding the developmental origins of health and disease (DOHaD). The structure of the fetal side of the placental vasculature is an important determinant of fetal growth and cardiovascular development. There are several imaging modalities for assessing feto-placental structure including stereology, electron microscopy, confocal microscopy, micro-computed tomography, light-sheet microscopy, ultrasonography and magnetic resonance imaging. In this review, we present current methodologies for imaging feto-placental vasculature morphology ex vivo and in vivo in human and experimental models, their advantages and limitations and how these provide insight into placental function and fetal outcomes. These imaging approaches add important perspective to our understanding of placental biology and have potential to be new tools to elucidate a deeper understanding of DOHaD.

KOKAN region is characterized by undernutrition across all stages of lifecycle. Developmental Origins of Health & Disease hypothesis suggests that environmental influences in the early period of growth and development can contribute to the risks of noncommunicable diseases (NCD) in adulthood. Newborns and placentas of 815 pregnant mothers delivered in a rural hospital were studied. We tested the hypothesis that low placental weight will be associated with low birth weight (LBW). Mothers had a mean age of 26 years and were smaller in size at delivery [mean height of 152.1 cm (±6.1 cm), weight 52 kg (±10.2 kg), body mass index (BMI) 22.5 kg/m2 (±4.1 kg/m2)]. Mean placental weight was 488 g (±120 g). Mean birth weight, length, and head circumference of the newborn were 2.54 kg (±0.5 kg), 46.3 cm (±3.1 cm), and 32.7 cm (±1.7 cm), respectively. Prevalence of LBW, stunting, and small head size was 41.6%, 42.2%, and 18.2%, respectively. Maternal height, weight, and BMI at delivery were all positively associated with placental weight (p < 0.01 for all). Mothers with placentas in the lowest placental weight tertile had an increased likelihood of producing an LBW baby [OR 7.7, 95% CI (5.0, 11.8)], a stunted baby [OR 1.9 (1.4, 2.9)], or a baby with a small head circumference [OR 2.4 (1.4, 4.0)]. Mothers in the lowest height tertile had odds of producing a LBW baby [OR 1.8 95% CI (1.2, 2.7)] or a stunted baby [OR 1.6 (1.1, 2.3)]. There is a need to improve the nutritional status of women in KOKAN region which may reduce the risk of NCD.

Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.