Fig 1
The placental barrier in the human term placenta. The figure represents a cross-section of the human placenta. The insert to the right shows a schematic illustration of the placental barrier, which at term mainly consists of the syncytiotrophoblast (ST) cell and the fetal capillary (FC) endothelial cell. Of these structures, it is primarily the two polarized syncytiotrophoblast plasma membranes, the microvillous plasma membrane (MVM) and the basal plasma membrane (BPM) that restrict the transfer of molecules like ions and amino acids. N, nucleus of syncytiotrophoblast cell; IVS, intervillous space; SA, spiral artery; VT, villous tree; UC, umbilical cord. Reproduced by permission from Elsevier Ltd.
Source publication
The mechanisms linking maternal nutrition to fetal growth and programming of adult disease remain to be fully established. We review data on changes in placental transport in response to altered maternal nutrition, including compromized utero-placental blood flow. In human intrauterine growth restriction and in most animal models involving maternal...
Contexts in source publication
Context 1
... an offspring that is smaller in size but who, in most instances, will survive and be able to reproduce. This reduced fetal growth is sometimes a better alternative than the fetus extracting all the nutrients needed for normal growth from an already deprived mother, thereby potentially jeopardizing both maternal and fetal survival. We speculate that the rela- tive importance of placental nutrient sensing and fetal demand signals for the regulation of placental function may differ between species and depend on the type, duration and severity of the nutritional perturbation. For example, it is plausible that regulation by fetal demand signals dominates when the nutritional challenge is moderate and brief, whereas regulation by placental nutrient sensing may override fetal demand if the nutritional challenge is severe and prolonged. Our long-term health is critically dependent on the availability of nutrients during fetal life, which is determined by placental transport. The understanding of the role of the placenta in fetal nutrition has evolved from the view that the placenta constitutes a selective but passive filter to the recognition that the placenta adapts to changes in maternal nutrition by responding to maternal nutritional cues, fetal demand signals and intrinsic nutrient-sensing signaling pathways. The complexity of these regulatory pathways is only beginning to be appreciated. A better understanding of the molecular mechanisms regulating placental transport functions may help to identify critical links between maternal nutrition, fetal growth and developmental programming. In addition, this knowledge is essential when designing novel intervention strategies. However, currently our understanding of these processes is limited, at best, presenting great challenges and opportunities for the future. For example, there is a lack of information on the (1) molecular identity of fetal demand signals, (2) the mechanisms by which lipids are transported across the placenta and the role of placental lipid transport in programming of obesity and diabetes, (3) how multiple placental nutrient-sensing signaling pathways are integrated and (4) how signals between the placenta and the mother influence maternal–fetal resource allocation. Furthermore, additional animal models that are relevant for the human condition are needed, in particular for GDM and maternal obesity. Finally, attention on the influence of fetal sex, ethnicity, maternal age and parity on placental function is required in future studies. Figure 1 is reproduced by permission from Elsevier Ltd; this figure was published in the chapter ‘Placental function and materno-fetal exchange’ in Fetal Medicine: Basic Science and Clinical Practice, 2 Ed, 2008, ISSN/ISBN 978-0-443-10408- 4. Supported by DK089989 (TLP), HD065007 (TJ and TLP), HD068370 (TJ) and HD071306 ...
Context 2
... nutrition has a profound impact on fetal development and growth and influences the future health of the offspring. 1,2 However, the mechanisms linking altered maternal nutrition to changes in fetal growth and developmental programming are poorly understood. Previous studies in rodents and sheep implicate changes in placental growth, structure and function as critical mediators of adverse pregnancy outcomes when maternal nutrient availability is altered. 3–9 Here, we review changes in placental nutrient transport in response to altered maternal nutrition in pregnant women and in relevant animal models. The concept of maternal nutrition is defined broadly as the ability of the maternal supply line to provide nutrients and oxygen to the placenta. Our discussion will therefore also include placental responses to compromized utero-placental blood flow, maternal hypoxia and iron deficiency. Fetal nutrient and oxygen availability depend on the rate of transfer across the ‘placental barrier’. In the human term placenta, there are only two cell layers separating fetal and maternal circulations; the fetal capillary endothelium and the syncytiotrophoblast (Fig. 1). 10 The syncytiotrophoblast is the transporting epithelium of the human placenta and has two polarized plasma membranes: the microvillous plasma membrane (MVM) directed toward maternal blood in the intervillous space and the basal plasma membrane (BPM) facing the fetal capillary. In the mouse and rat placenta, three trophoblast layers form the placental barrier, and accumulating evidence suggests that the maternal-facing plasma membrane of trophoblast layer II of the mouse placenta is functionally analogous to the MVM in the human placenta. 11 In the hemochorial placenta of primates and rodents, the trophoblast is directly in contact with maternal blood. However, in the synepitheliochorial placenta of the sheep the maternal capillary endothelium and uterine epithelium remain intact and fetal binucleate cells migrate and fuse with the uterine epithelium, creating a syncy- tium of mixed maternal and fetal origin. 12,13 Net maternal–fetal transfer is influenced by a multitude of factors. These include utero-placental and umbilical blood flows, available exchange area, barrier thickness, placental metabolism, concentration gradients and transporter expression/activity in the placental barrier. Placental transfer of highly permeable molecules such as oxygen is non-mediated and particularly influenced by changes in barrier thickness, concentration gradients, placental metabolism and blood flow. 14 In contrast, the rate-limiting step for maternal–fetal transfer of many ...
Similar publications
Intrauterine growth restriction increases the risk of perinatal complications and predisposes the infant to diabetes and cardiovascular disease in later life. Mechanisms by which maternal nutrient restriction (MNR) reduces fetal growth are poorly understood.
MNR decreases placental amino acid (AA) transporter activity, leading to reduced transplace...
Placental insufficiency leading to intrauterine growth restriction (IUGR) demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that...
Syncytiotrophoblast lines the intervillous space of the placenta and plays important roles in fetus growth throughout gestation. However, perturbations at the maternal-fetal interface during placental malaria may possibly alter the physiological functions of syncytiotrophoblast and therefore growth and development of the embryo
in utero
. An unders...
Citations
... dietary patterns with excessive or deficient intakes of macronutrients have profound effects on embryonic and fetal growth [5][6][7][8][9][10][11][12][13][14]. Impairments of growth at such early stages of development are risk factors for pregnancy complications and non-communicable diseases in adult life [15,16]. ...
The required intake of macronutrients by women during the periconceptional period for optimal fetal growth is the subject of ongoing investigation. Intake of polyunsaturated fatty acids (PUFA) is positively associated with fetal neural development, growth velocity and birth weight. However, limited evidence indicates that PUFAs play a role in embryogenesis. We aim to investigate the associations between maternal PUFA dietary intake and first trimester embryonic volume (EV) and head volume (HV). In a prospective cohort study (2013–2020), 464 pregnant women at < 8 weeks of gestation were included. Maternal dietary intake of PUFAs, including omega 3 (docosahexaenoic acid, DHA and eicosapentaeonic acid, EPA) and 6, was obtained from food frequency questionnaires, and first trimester three-dimensional ultrasound examinations were performed to measure EV and HV using Virtual Reality techniques. More than 70% of the population had omega 3 intakes below recommendations. A higher intake of PUFAs was associated with a smaller embryonic HV/EV ratio after adjusting for confounders (EPA p = 0.012, DHA p = 0.015, omega 3 and 6 p < 0.001), but no associations were found with EV or HV alone. Omega 3 from fish oil supplements alone was not associated with embryonic growth. Strong adherence to a PUFA-rich dietary pattern was associated with a smaller embryonic HV/EV ratio (DHA and EPA-rich diet p = 0.054, PUFA-rich diet p = 0.002). It is important to increase awareness of the high prevalence of omega 3-deficiency among pregnant women, and the opportunity for prevention by increasing PUFA intake, thereby reducing the risks of adverse pregnancy outcomes which originate during the periconceptional period.
... Open Veterinary Journal, (2024), Vol. 14(11): 2924-2935 overweight mother, which came with a line of evidence that both conditions were linked to chronic, low-grade inflammation in the mother, which may be detrimental to placental development by increasing its inflammation and so reducing the fetus's access to nutrients (Gaccioli et al., 2013), yielding adverse pregnancy outcomes and poor fetal development (Basatemur et al., 2013;Yu et al., 2013). ...
Background
Cognitive impairment and attention deficit disorder have been on the rise among generations in recent times. A significant portion of the brain involved in learning and cognition is the hippocampus. Its development begins in utero till weaning. The mother’s body mass index (BMI) before pregnancy indicates her health; however, little data links maternal BMI before pregnancy to fetal hippocampal health outcomes.
Aim
The study aimed to estimate the extent to which pre-pregnancy maternal BMI relates to their offspring brain status, and thus to what extent to this stage of life may be an opportunity for mental and cognitive development.
Methods
Thirty-six naive female albino rats (Rattus norvegicus) at 8 weeks of age with an average weight of 190–220 g body weight were obtained and assigned to three experimental groups according to their body mass index into; under-, over-, and normal weight. Following one week of habituation, all females were allowed to mate (3 female/ 1 male). On postnatal day 1 (PND1), pups were randomly adjusted to 8/dam with an equal gender ratio. On 15 days postpartum, all pups were sacrificed. Hippocampi were removed and processed for histological investigations, Glial fibrillary acidic protein immunohistochemically, and flow cytometric assessments of apoptosis. Measurements of the cognitive brain were carried out.
Results
The present findings manifested elevation in the inflammatory and apoptotic markers in the hippocampus of underweight mothers-offspring yielding a lower cognitive ability than overweight mothers-offspring compared to those whose mothers with normal weight before conception. The male offspring were more affected than female offspring especially those born to pre-pregnancy underweight mothers.
Conclusion
The study concluded that there may be a connection between a mother’s pre-pregnancy BMI and her offspring’s cognitive capacities, which calls for more study to gain a deeper knowledge and to create interventions that target the physical health of the mother prior to pregnancy in order to enhance their offspring’s health and cognitive outcomes.
... Placenta plays a key role in the regulation of nutrient distribution between mother and fetus during pregnancy, as it integrates the signals on the maternal and fetal nutrient availability [4]. The main placental sensor of the nutrient level in the mother's blood is the mTORC1 complex containing mammalian target of rapamycin (mTOR) as a catalytic unit [5,6]. ...
... The 'foetal demand model' states that the foetus determines the energy supply and placental growth and therefore is independent of maternal body condition. On the other hand, the 'placental nutrient sensing model' argues that the nutritional supply is dependent on maternal energy availability (Gaccioli et al., 2013). Murine genetic models have proven that disproportionally large placentas can lower the nutrient supply per gram of placenta to the foetus. ...
... Low-protein diets reduce maternal amino acid levels and their transfer across the placenta to the fetus and to suckling pups during lactation (35)(36)(37). Despite hyperplasia and upregulation of amino acid transporters, the placenta is unable to restore adequate amino acid transfer to the fetus when the deficiency persists throughout gestation (38)(39)(40)(41). Consequently, the offspring have lower birth weights and an altered physiology that attempts to compensate for the sustained amino acid deficiency (42)(43)(44). ...
Fetal brain development requires increased maternal protein intake to ensure that offspring reach their optimal cognitive potential in infancy and adulthood. While protein deficiency remains a prevalent issue in developing countries, it is also reemerging in Western societies due to the growing adoption of plant-based diets, some of which are monotonous and may fail to provide sufficient amino acids crucial for the brain’s critical developmental phase. Confounding variables in human nutritional research have impeded our understanding of the precise impact of protein deficiency on fetal neurodevelopment, as well as its implications for childhood neurocognitive performance. Moreover, it remains unclear whether such deficiency could predispose to mental health problems in adulthood, mirroring observations in individuals exposed to prenatal famine. In this review, we sought to evaluate mechanistic data derived from rodent models, placing special emphasis on the involvement of neuroendocrine axes, the influence of sex and timing, epigenetic modifications, and cellular metabolism. Despite notable progress, critical knowledge gaps remain, including understanding the long-term reversibility of effects due to fetal protein restriction and the interplay between genetic predisposition and environmental factors. Enhancing our understanding of the precise mechanisms that connect prenatal nutrition to brain development in future research endeavors can be significantly advanced by integrating multiomics approaches and utilizing additional alternative models such as nonhuman primates. Furthermore, it is crucial to investigate potential interventions aimed at alleviating adverse outcomes. Ultimately, this research has profound implications for guiding public health strategies aimed at raising awareness about the crucial role of optimal maternal nutrition in supporting fetal neurodevelopment.
... The de novo development of blood vessels (vasculogenesis) and the expansion and elongation of pre-existing blood vessels (angiogenesis) are responsible for the development of the new vascular beds during the embryonic and post-embryonic periods, respectively [1][2][3][4]6]. Both processes depend on angiogenic/anti-angiogenic factors, including placental growth factor (PlGF), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), and nitric oxide (NO) [3,7,13,14]. While not typically considered primary angiogenic factors, eNOS2 and eNOS3, which generate the potent angiogenic factor NO from arginine, play roles in angiogenesis. ...
... While not typically considered primary angiogenic factors, eNOS2 and eNOS3, which generate the potent angiogenic factor NO from arginine, play roles in angiogenesis. It is important to keep in mind that these factors are also being secreted into the maternal circulation, and in conjunction with hormones, act to enable adequate maternal adaptation to pregnancy, including increased cardiac output and blood volume, while at the same time inducing vasodilatation of resistance vessels to avoid high maternal blood pressure [3,7,13]. ...
The effect of vitamins and minerals supplementation (VTM) and/or two rates of body weight gain (GAIN) on bovine placental vascular development and angiogenic factors gene expression were evaluated in two experiments: In Exp. 1, crossbred Angus heifers (n = 34) were assigned to VTM/NoVTM treatments at least 71 days before breeding to allow changes in the mineral status. At breeding, through artificial insemination (AI), heifers were assigned to low-gain (LG) 0.28 kg/d or moderate-gain (MG) 0.79 kg/d treatments, resulting in NoVTM-LG (Control; n = 8), NoVTM-MG (n = 8), VTM-LG (n = 9), and VTM-MG (n = 9) until day 83 of gestation; In Exp. 2, crossbred angus heifers (n = 28), were assigned to control (CON; n = 12), receiving a basal total mixed ration (TMR) or TMR + VTM (VTM; n = 16) from breeding until parturition. Placentomes from Exp. 1 and cotyledons (COT) from Exp. 2 were evaluated by immunohistochemistry for COT vascular density area. COTs from Exp. 1 were evaluated for angiogenic factor (ANGPT-1, ANGPT-2, eNOS2, eNOS3, FLT1, KDR, TEK, VEGFA) gene expression. In Exp. 1, COT vascularity was not affected by the interaction of VTM and GAIN (p = 0.67) or the main effects of VTM (p = 0.50) and GAIN (p = 0.55). Likewise, angiogenic factors were not differentially expressed between treatments (p < 0.05). In Exp. 2, COT vascularity was greater in VTM vs. CON (p = 0.07). In conclusion, there is a suggested later-stage influence of vitamin and mineral supplementation on placental vascularity, emphasizing the importance of supplementation beyond early pregnancy.
... In GDM, the intrauterine environment changes due to an excess of nutrients like glucose, fatty acids, and amino acids [3][4][5]. These circumstances affect placental endothelial development during the villous maturation and differentiation stage, leading to an increase in branching angiogenesis and vascular surface [6]. ...
Background
Gestational diabetes mellitus (GDM), a type of diabetes that occurs for the first time during pregnancy, may predispose the development of chronic degenerative diseases and metabolic alterations in mother and offspring. DNA methylation and microRNA (miRNA) expression are regulatory mechanisms of gene expression that may contribute to the pathogenesis of GDM. Therefore, we determined global DNA methylation and miR-126-3p expression levels in 8 and 7 Mexican women with and without GDM, respectively.
Methods and results
Global DNA methylation was assessed by measuring the percentage of 5-methylcytosine (5-mC) in placenta, umbilical cord, and plasma DNA samples, whereas miR-126-3p expression was quantified by real-time PCR using the 2−ΔCt method of the corresponding RNA samples. A significant increase in the percentage of 5-mC was detected in placenta samples from GDM patients compared to healthy women, while plasma samples showed a significant decrease. Conversely, miR-126-3p expression levels were significantly higher in plasma from the GDM group, while placenta and umbilical cord samples showed no significant differences across experimental groups. Furthermore, DNA methylation correlated significantly with glucose levels in placenta and plasma. Likewise, miR-126-3p expression correlated significantly with plasma glucose, in addition to maternal body mass index (BMI at first trimester).
Conclusion
The results indicate that GDM is associated with alterations in global DNA methylation levels and miR-126-3p expression in placenta and/or plasma, providing insights into future novel approaches to diagnose and/or prevent this pathology.
... In contrast, homeostatic regulation predicts that signals from a fetus deprived of nutrients would tend to upregulate nutrient transport in the placenta, largely a fetal organ. Thus, our model ( Fig. 1) based on published data (for example Dabelea et al., 2008;Fisk and Atun, 2008;Gaccioli et al., 2013;Hemberger et al., 2020;Jansson et al., 2008;Aye et al., 2014;James-Allan et al., 2020) suggests that, with respect to regulation of placental function, maternal supply signals dominate over fetal demand signals. We speculate that this regulatory system involving placental mTOR signaling has developed in response to the evolutionary pressure from maternal undernutrition or starvation. ...
Compelling epidemiological and animal experimental data demonstrate that cardiometabolic and neuropsychiatric diseases originate in a suboptimal intrauterine environment. Here, we review evidence suggesting that altered placental function may, at least in part, mediate the link between the maternal environment and changes in fetal growth and development. Emerging evidence indicates that the placenta controls the development and function of several fetal tissues through nutrient sensing, modulation of trophoblast nutrient transporters and by altering the number and cargo of released extracellular vesicles. In this Review, we discuss the development and functions of the maternal-placental-fetal interface (in humans and mice) and how cross-talk between these compartments may be a mechanism for in utero programming, focusing on mechanistic target of rapamycin (mTOR), adiponectin and O-GlcNac transferase (OGT) signaling. We also discuss how maternal diet and stress influences fetal development and metabolism and how fetal growth restriction can result in susceptibility to developing chronic disease later in life. Finally, we speculate how interventions targeting placental function may offer unprecedented opportunities to prevent cardiometabolic disease in future generations.
... These metabolic memories depend on epigenetic mechanisms [83]. GDM is characterized by intrauterine over-nutrition with excess glucose, fatty acids, and amino acids [8,[84][85][86], leading to epigenetic alterations [8]. ...
Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body's microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life.
... Макросомия обычно определяется как вес при рождении выше 90-го процентиля для гестационного возраста или >4000 г. Существует высокая корреляция между весом плаценты и весом при рождении [23]. Патофизиологию макросомии можно объяснить гипергликемией матери, вызванной резистентностью к инсулину, что приводит к повышенному плацентарному транспорту глюкозы и эндогенной секреции инсулина у плода. ...
Актуальность: Женское ожирение – это сложное многофакторное заболевание, при котором существует множество механизмов, участвующих в воздействии избыточного веса и ожирения на развитие репродуктивных расстройств. Важными механизмами являются резистентность к инсулину, гиперинсулинемия и гиперандрогения, липотоксичность и воспаление. Однако точный механизм, касающийся их взаимосвязи, до сих пор неясен. Избыточная жировая ткань ароматизирует андрогены в эстроген, что приводит к отрицательной обратной связи на гипоталамо-гипофизарной оси и наконец, к снижению выработки гонадотропинов, а более низкий уровень гонадотропинов приводит к угнетению активности яичников и к нарушениям менструального цикла и бесплодию. Так же, нарушение восприимчивости эндометрия у женщин с ожирением является причиной неудачной имплантации эмбриона и бесплодия. Как известно, женское ожирение стало глобальной проблемой, которая в большинстве случаев сопровождается эндокринными и метаболическими расстройствами. Женщины с ожирением с большей вероятностью сталкиваются с репродуктивными проблемами, включая бесплодие, дефекты эмбрионального развития и аномалии у потомства. В этой связи, актуальность данной темы неоспорима. Цель исследования – изучить влияние ожирения на фертильность женщин репродуктивного возраста. Материалы и методы: Были использованы англоязычные статьи, найденные в поисковых системах PubMed, Scopus, Google Scholar, e-Library по ключевым словам и медицинским тематическим заголовкам среди материалов, опубликованных с 2012 по 2022 гг. В обзор было включено 26 статей, посвященных патогенезу, этиологии, влиянию и лечению ожирения в репродуктивном возрасте. Исследования были проведены с соблюдением применимых этических принципов. Результаты: Ожирение имеет предполагаемое влияние на фертильность, но знаний о физиопатологии данного процесса недостаточно. Лечение должно быть направлено на минимальное вмешательство, необходимое для восстановления фертильности. Нарушение функций плаценты из-за ожирения матери может быть связано с развитием ограничения роста плода, и плод не достигает своего полного потенциала роста. Потеря веса может помочь улучшить овуляцию, беременность и живорождение, и поэтому женщинам с высоким индексом массы тела следует рекомендовать сбросить вес до зачатия. Заключение: Ожирение у женщин сопряжено с риском бесплодия и негативными последствиями для плода. К счастью, этих неблагоприятных последствий можно избежать при умеренной потере веса. Для улучшения здоровья большего числа женщин необходимы более глубокие исследования, чтобы лучше понять взаимосвязь между ожирением и женской репродуктивной системой.
