Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1913 2022-11-01 09:20:37 |
2 update references and layout Meta information modification 1913 2022-11-03 07:14:53 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Basak, S.;  Das, R.K.;  Banerjee, A.;  Paul, S.;  Pathak, S.;  Duttaroy, A.K. Maternal Obesity and Gut Microbiota. Encyclopedia. Available online: (accessed on 16 June 2024).
Basak S,  Das RK,  Banerjee A,  Paul S,  Pathak S,  Duttaroy AK. Maternal Obesity and Gut Microbiota. Encyclopedia. Available at: Accessed June 16, 2024.
Basak, Sanjay, Ranjit K. Das, Antara Banerjee, Sujay Paul, Surajit Pathak, Asim K. Duttaroy. "Maternal Obesity and Gut Microbiota" Encyclopedia, (accessed June 16, 2024).
Basak, S.,  Das, R.K.,  Banerjee, A.,  Paul, S.,  Pathak, S., & Duttaroy, A.K. (2022, November 01). Maternal Obesity and Gut Microbiota. In Encyclopedia.
Basak, Sanjay, et al. "Maternal Obesity and Gut Microbiota." Encyclopedia. Web. 01 November, 2022.
Maternal Obesity and Gut Microbiota

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring.

obesity pregnancy microbiota placenta brain development fetal development

1. Introduction

Obesity during pregnancy is a rising public health concern rapidly increasing worldwide [1][2][3]. Excessive maternal weight gain during pregnancy is consistently associated with many adverse impacts, including neurocognitive outcomes in the offspring [1][4]. Recently, the effect of obesity in pregnancy on maternal and fetal health has been reviewed [5][6]. The adverse effect of maternal obesity on the fetal programming of adult diseases extends beyond non-communicable diseases to brain diseases [7][8]. Obesity and a high-fat diet predispose offspring to adverse cardiometabolic and neurodevelopmental outcomes [9]. In addition, maternal high-fat intake during pregnancy was associated with an elevated risk of neuropsychiatric disorders such as hyperactivity/attention-deficit disorder/anxiety and depressive-like behaviours later in life in offspring [10][11][12][13][14][15][16][17][18]. Both obesity and a high-fat diet can impact maternal lipid metabolic state and gut microbial composition and affect offspring’s metabolic health and brain development [19][20]. Available data from extensive epidemiologic studies indicate an association between maternal obesity and adverse neurodevelopmental outcomes in human offspring. Maternal diet, adiposity, peripheral inflammation, and gut microbiota are the potential mechanisms for underlying changes in offspring brains and behaviour [20][21][22][23].
The diversity of intestinal microbiota during pregnancy has emerged as an essential factor as their metabolites can affect the host’s health in multiple ways, from lipid metabolism to brain development and function. The microbiota-gut axis can regulate maternal obesity, diet, lifestyle and physical activity. Gut microbiota produces neurotransmitters and neuromodulators (e.g., serotonin, GABA, SCFAs and their metabolites) and their derivatives in the circulation. These bioactive factors are transported to the brain via blood vessels after crossing the BBB and modulate the neonate’s cognitive development and brain-mediated performance activities. A steady-state microbiota of the mother is determined by several extrinsic (environment, geography, lifestyle) and intrinsic (genetics, mode of delivery, eating habits, age, infection, stress, medication) factors. While one-third of the gut microbial composition is common in most individuals, the remaining two-thirds are specific to the individual [24]. Despite these, not much data is available on maternal obesity during pregnancy and the modulation of gut microbial composition and diversity on the brain development of the offspring.

2. Impacts of Obesity on Maternal Endocrine Factors and Fetal Brain Development

In pregnancy, the maternal metabolism changes dramatically to support fetal growth and meet maternal additional energy requirements. However, maternal obesity in pregnancy increases maternal complications and enhances the risk of developing obesity, cardiovascular disease, diabetes, and cognitive dysfunction in offspring in adult life [25][26]. Obesity-induced metaflammation results in aberrant changes at the cellular and humoral levels that contribute to pregnancy complications. However, the physiological inflammatory process favours implantation, placental development, and parturition [27]. Complex interactions mediate adverse effects of obesity between metabolic, inflammatory, and oxidative stress homeostasis. Obesity in pregnancy is associated with elevated levels of pro-inflammatory cytokines such as interleukin 6 (IL-6), IL-1β, IL-8, and monocyte chemotactic protein-1 (MCP-1) in both the placenta and in maternal plasma [28][29]. The maternal obesity-induced swing toward a pro-inflammatory state can affect the neurometabolic state of the fetus.
Obesity-induced changes in maternal hormone levels can affect gene expression involved in fetal brain growth and development [30][31]. Obese pregnant women possess an increased risk of developing thyroid dysfunction during gestation. Maternal hormones such as thyroid and glucocorticoids affect fetal brain development. The hormones’ effects on brain development are time- and concentration-dependent [32]. Since obesity is associated with hypothyroidism and consequently affects brain development [33]. Maternal thyroid metabolism is also disturbed by maternal iodine deficiency, environmental endocrine modifiers, and other intrinsic factors associated with thyroid diseases [34].
In early pregnancy, thyroid hormones are needed for brain developmental processes such as neuronal migration, differentiation of neurons, glial cells, neurogenesis, and synaptogenesis [35][36]. Thyroid hormones regulate gene expression in the cell cycle and intracellular signalling, cytoskeleton organization, extracellular matrix proteins and several cellular adhesion factors involved in neuronal migration and neurogenesis [35][37]. In addition, thyroid hormones are also involved in neuronal migration and neuron development by regulating reelin and neurogenin 2 genes [37]. Therefore, optimum maternal thyroid function is critically required for fetal neurodevelopment.
The altered thyroid hormone levels result in severe neurological deficiency and mental disability [38]. In addition, thyroid deficiency during pregnancy may drive offspring to the later onset of neurodevelopmental disorders [34][39][40]. Several neurodevelopmental deficits are observed in offspring born from mothers with thyroid dysfunction during the first half of gestation [41][42]. Even babies of the mother with asymptomatic thyroid dysfunction are at increased risk of impaired brain development [43]. The adverse subclinical hypothyroidism on fetal neurocognitive development is less specific. Maternal hypothyroxinemia occurs in mild iodine deficiency and may result in neurodevelopmental problems.
Corticosteroids in late gestation are indispensable for fetal brain maturation [44]. The developing brain is susceptible to corticosteroid-induced stress [45]. A study showed that prenatal maternal stress increased glucocorticoids, and a high-fat diet, increased the risk of developing obesity in offspring in later life [46]. Chronic activation of glucocorticoid receptors alters the levels of glucocorticoid in hippocampal and hypothalamic regions, thus modifying feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis [47]. Corticosteroid effects are also mediated via epigenetic changes in genes associated with synaptic plasticity [48].
Stress hormones such as catecholamines, vasopressin, and oxytocin affect fetal brain development and functionalities [49]. Chronically increased cortisol levels in maternal stress result in lower levels of maternal T4 available for the fetal brain, thus affecting fetal brain development [50].
In addition to thyroid and glucocorticoid, several other hormones play roles in fetal neurodevelopment [51]. Maternal obesity and abnormal hormone levels affect fetal programming beyond the endocrine and cardiovascular systems to the brain. Several studies showed an association between high maternal BMI and adverse neurodevelopmental functions in their progenies (Table 1).
Table 1. Epidemiological studies on maternal obesity and neurodevelopment of the offspring.
Observations References
Increased odds of developing autism spectrum disorders in offspring of obese. [52][53][54][55]
Increases odds of cognitive deficits in children of obese women observed in cohorts. [55][56][57][58][59][60]
Obese mothers have twice as likely to have a child with mental developmental delay. [58][61]
An increase in autism in children was reported in prospective pregnancy cohorts [62]
The maternal obesity was associated with schizophrenia in adult offspring in a large retrospective cohort study but other studies could not confirm this association. [63][64]
A dose-dependent increase in relative risk of cerebral palsy as maternal BMI was observed. [13][65][66][67]

3. The Placenta of an Obese Mother and Its Impact on Fetal Brain Development

An increase in total lipid content characterizes the placentas of obese women at term, infiltrated neutrophils, foam-loaded macrophages and increased levels of pro-inflammatory mediators [68][69]. The maternal obesity induced-metabolic changes affect early placental growth, gene expression, and subsequent placental structure and function, which becomes clinically manifest in late pregnancy [70]. Placental dysfunctions may adversely affect fetal development [71]. In early pregnancy, the human placenta also responds to elevated maternal insulin in obese women. Obesity in pregnancy affects human placental structure and function in many ways. The cellular signalling system may mediate these effects by modulating inflammation, metabolism, and oxidative stress pathways. These placental alterations affect pregnancy outcomes independently and synergistically with other risk factors [6][72]. The placenta is enriched with a complex vascularization for fetal blood supply that requires extensive angiogenesis. Sub-optimal angiogenesis leads to abnormal placental size and vasculature. Dysregulated angiogenesis in the placenta may directly or indirectly involve pregnancies, including pre-eclampsia, pre-term birth [73], GDM [74], and IUGR [75]. The n-3 fatty acids deficiency reduced the placental transfer of fatty acids in pre-eclampsia and GDM -associated fetuses [76]. Abnormal placental vasculature is present in several pathological conditions, such as pre-term birth, intrauterine growth restriction (IUGR), and pre-eclampsia. Suboptimal placental angiogenesis is contributed by genetics, dietary and lifestyle factors [77]. Optimal placentation is facilitated by several angiogenic factors such as vascular endothelial growth factor A (VEGFA), angiopoietin-like 4 (ANGPTL4), fibroblast growth factor (FGF), and placental growth factor (PlGF), as well as docosahexaenoic acid, 22:6 n-3 (DHA) [78][79].
High-fat diets and maternal obesity alter the metabolome and early changes in the placental transcriptome and decrease placenta vascularity [80]. During pregnancy, a maternal high-fat diet promotes ectopic lipid deposition, leading to lipotoxicity and chronic inflammation in the placenta [81]. Further, the high-fat diet enforces the placenta to adapt its metabolic response and structural change (thickness) by altering angiogenesis. Animal studies showed reduced placental labyrinth depth and elevated expression of insulin-like growth factor 2 (IGF2) and its receptor genes in the fetuses of high-fat diet dams [82]. The n-3 polyunsaturated fatty acids (n-3 PUFA) deficiency resembles high-fat diet-induced impaired placental phenotypes. The maternal n-3 PUFA deficiency affected the vascular development of decidua; the feto-placental unit suggests impacts of maternal fatty acid status on placental vascularity [83].
The lipid accumulation in the obese placenta results from altered activities of fatty acid transporter expression, lipoprotein lipase, and alterations to mitochondrial oxidative metabolism [84][85]. A recent analysis of the genome-wide transcriptome, epigenetics, and proteomics showed the effects of maternal obesity on placental lipid transport and metabolism [86][87]. Altered lipid transport and metabolism of the obese placenta, as reflected by the changes in fatty acid transporters expression, had adverse effects on smooth placental functioning in transport and the metabolism of lipids across the feto-placental unit [88][89][90]. The obese placenta had high total lipids, triglycerides, free fatty acids, and cholesterol levels. Obese placental phenotype favours excess lipid storage with reduced lipid transport to the developing fetus, including long-chain polyunsaturated fatty acids (LCPUFAs) essentially required for fetal brain development [85]. Optimal PUFA is critical for feto-placental development, and any changes, as in obesity, can have adverse effects on fetal brain development [91][92].
The pro-inflammatory cascade is favoured by an increased ratio of pro-inflammatory M1 over anti-inflammatory M2 macrophages during maternal obesity. In addition, obesity may further enhance pathological pregnancies, such as pre-eclampsia, by reducing the uterine natural killer (uNK) cell populations [93]. Furthermore, maternal obesity was associated with epigenetic dysregulations in leptin and adiponectin secretions [94]. Thus, dysregulated endocrine controls in the term placenta deprive protective effects of these adipokines on placental development, indicating the placenta’s adaptation to a harmful maternal environment. Maternal obesity and gestational diabetes mellitus (GDM) also affect fatty acid transport across the placenta. Increased placental fatty acid binding protein 4 (FABP4) and endothelial lipase expression were observed in obese women with diabetes [95][96]. In contrast, reduced levels of FABP5 and lowered uptake of n-6 LCPUFAs were reported in obese placentas [68][87][97]. Both low and high expressions of fatty acid translocase CD36/FAT were observed in the placenta of obese women [90][97].
Inflammation and metabolic dysfunction, as observed in obesity, increase placental oxidative, endoplasmic reticulum stress and downstream activation of the placental unfolded protein response, all of which have been associated with pregnancy complications, such as fetal growth restriction, pre-eclampsia, and gestational diabetes. Amounts of estradiol and progesterone concentrations in plasma and placenta are reduced in obese women than in lean women [98]. The obese placenta is exposed to high insulin in early pregnancy, which produces altered steroid hormones in mitochondria and affects energy metabolism.
Maternal lipid transport and metabolism regulate fetal adiposity via placental function. The placental transport of maternal lipids is compromised during pathological states such as IUGR and GDM. The inefficient placental LCPUFAs transfers and fat-soluble vitamins may induce metabolic dysfunction and decreased fetal growth. In GDM, the interplay of the placental ANGPTL4-lipoprotein lipase is responsible for fetal adiposity [99].


  1. Catalano, P.M.; Shankar, K. Obesity and pregnancy: Mechanisms of short term and long term adverse consequences for mother and child. BMJ 2017, 356, j1.
  2. Chen, C.; Xu, X.; Yan, Y. Estimated global overweight and obesity burden in pregnant women based on panel data model. PLoS ONE 2018, 13, e0202183.
  3. Kominiarek, M.A.; Peaceman, A.M. Gestational weight gain. Am. J. Obstet. Gynecol. 2017, 217, 642–651.
  4. Lahti-Pulkkinen, M.; Bhattacharya, S.; Wild, S.H.; Lindsay, R.S.; Raikkonen, K.; Norman, J.E.; Bhattacharya, S.; Reynolds, R.M. Consequences of being overweight or obese during pregnancy on diabetes in the offspring: A record linkage study in Aberdeen, Scotland. Diabetologia 2019, 62, 1412–1419.
  5. Creanga, A.A.; Catalano, P.M.; Bateman, B.T. Obesity in Pregnancy. N. Engl. J. Med. 2022, 387, 248–259.
  6. Dunlop, A.L.; Mulle, J.G.; Ferranti, E.P.; Edwards, S.; Dunn, A.B.; Corwin, E.J. Maternal Microbiome and Pregnancy Outcomes That Impact Infant Health: A Review. Adv. Neonatal Care 2015, 15, 377–385.
  7. Boney, C.M.; Verma, A.; Tucker, R.; Vohr, B.R. Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005, 115, e290–e296.
  8. Leon, D.A.; Lithell, H.O.; Vagero, D.; Koupilova, I.; Mohsen, R.; Berglund, L.; Lithell, U.B.; McKeigue, P.M. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: Cohort study of 15 000 Swedish men and women born 1915–1929. BMJ 1998, 317, 241–245.
  9. Neri, C.; Edlow, A.G. Effects of Maternal Obesity on Fetal Programming: Molecular Approaches. Cold Spring Harb. Perspect. Med. 2015, 6, a026591.
  10. DeCapo, M.; Thompson, J.R.; Dunn, G.; Sullivan, E.L. Perinatal Nutrition and Programmed Risk for Neuropsychiatric Disorders: A Focus on Animal Models. Biol. Psychiatry 2019, 85, 122–134.
  11. Thompson, J.R.; Gustafsson, H.C.; DeCapo, M.; Takahashi, D.L.; Bagley, J.L.; Dean, T.A.; Kievit, P.; Fair, D.A.; Sullivan, E.L. Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates. Front. Endocrinol. 2018, 9, 161.
  12. Torres-Espinola, F.J.; Berglund, S.K.; Garcia-Valdes, L.M.; Segura, M.T.; Jerez, A.; Campos, D.; Moreno-Torres, R.; Rueda, R.; Catena, A.; Perez-Garcia, M.; et al. Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age—A Follow Up from the PREOBE Cohort. PLoS ONE 2015, 10, e0133010.
  13. Mehta, S.H.; Kerver, J.M.; Sokol, R.J.; Keating, D.P.; Paneth, N. The association between maternal obesity and neurodevelopmental outcomes of offspring. J. Pediatr. 2014, 165, 891–896.
  14. Gustafsson, H.C.; Sullivan, E.L.; Battison, E.A.J.; Holton, K.F.; Graham, A.M.; Karalunas, S.L.; Fair, D.A.; Loftis, J.M.; Nigg, J.T. Evaluation of maternal inflammation as a marker of future offspring ADHD symptoms: A prospective investigation. Brain Behav. Immun. 2020, 89, 350–356.
  15. Andersen, C.H.; Thomsen, P.H.; Nohr, E.A.; Lemcke, S. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur. Child Adolesc. Psychiatry 2018, 27, 139–148.
  16. Edlow, A.G. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenat. Diagn. 2017, 37, 95–110.
  17. Sullivan, E.L.; Grayson, B.; Takahashi, D.; Robertson, N.; Maier, A.; Bethea, C.L.; Smith, M.S.; Coleman, K.; Grove, K.L. Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. J. Neurosci. 2010, 30, 3826–3830.
  18. Thompson, J.R.; Valleau, J.C.; Barling, A.N.; Franco, J.G.; DeCapo, M.; Bagley, J.L.; Sullivan, E.L. Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates. Front. Endocrinol. 2017, 8, 164.
  19. Hamad, A.F.; Alessi-Severini, S.; Mahmud, S.M.; Brownell, M.; Kuo, I.F. Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study. PLoS ONE 2019, 14, e0221921.
  20. Vuong, H.E.; Pronovost, G.N.; Williams, D.W.; Coley, E.J.L.; Siegler, E.L.; Qiu, A.; Kazantsev, M.; Wilson, C.J.; Rendon, T.; Hsiao, E.Y. The maternal microbiome modulates fetal neurodevelopment in mice. Nature 2020, 586, 281–286.
  21. Tong, L.; Kalish, B.T. The impact of maternal obesity on childhood neurodevelopment. J. Perinatol. 2021, 41, 928–939.
  22. Dunn, G.A.; Mitchell, A.J.; Selby, M.; Fair, D.A.; Gustafsson, H.C.; Sullivan, E.L. Maternal diet and obesity shape offspring central and peripheral inflammatory outcomes in juvenile non-human primates. Brain Behav. Immun. 2022, 102, 224–236.
  23. Guzzardi, M.A.; Ederveen, T.H.A.; Rizzo, F.; Weisz, A.; Collado, M.C.; Muratori, F.; Gross, G.; Alkema, W.; Iozzo, P. Maternal pre-pregnancy overweight and neonatal gut bacterial colonization are associated with cognitive development and gut microbiota composition in pre-school-age offspring. Brain Behav. Immun. 2022, 100, 311–320.
  24. Parashar, A.; Udayabanu, M. Gut microbiota: Implications in Parkinson’s disease. Parkinsonism Relat. Disord. 2017, 38, 1–7.
  25. Kelly, A.C.; Powell, T.L.; Jansson, T. Placental function in maternal obesity. Clin. Sci. 2020, 134, 961–984.
  26. Brombach, C.; Tong, W.; Giussani, D.A. Maternal obesity: New placental paradigms unfolded. Trends Mol. Med. 2022, 28, 823–835.
  27. St-Germain, L.E.; Castellana, B.; Baltayeva, J.; Beristain, A.G. Maternal Obesity and the Uterine Immune Cell Landscape: The Shaping Role of Inflammation. Int. J. Mol. Sci. 2020, 21, 3776.
  28. Pantham, P.; Aye, I.L.; Powell, T.L. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 2015, 36, 709–715.
  29. Yang, X.; Li, M.; Haghiac, M.; Catalano, P.M.; O’Tierney-Ginn, P.; Hauguel-de Mouzon, S. Causal relationship between obesity-related traits and TLR4-driven responses at the maternal-fetal interface. Diabetologia 2016, 59, 2459–2466.
  30. Brunton, P.J.; Russell, J.A. Neuroendocrine control of maternal stress responses and fetal programming by stress in pregnancy. Prog. Neuropsychopharmacol. Biol. Psychiatry 2011, 35, 1178–1191.
  31. Morreale de Escobar, G.; Obregon, M.J.; Escobar del Rey, F. Role of thyroid hormone during early brain development. Eur. J. Endocrinol. 2004, 151 (Suppl. S3), U25–U37.
  32. Auyeung, B.; Lombardo, M.V.; Baron-Cohen, S. Prenatal and postnatal hormone effects on the human brain and cognition. Pflug. Arch. 2013, 465, 557–571.
  33. Song, R.H.; Wang, B.; Yao, Q.M.; Li, Q.; Jia, X.; Zhang, J.A. The Impact of Obesity on Thyroid Autoimmunity and Dysfunction: A Systematic Review and Meta-Analysis. Front. Immunol. 2019, 10, 2349.
  34. Min, H.; Dong, J.; Wang, Y.; Wang, Y.; Teng, W.; Xi, Q.; Chen, J. Maternal Hypothyroxinemia-Induced Neurodevelopmental Impairments in the Progeny. Mol. NeuroBiol. 2016, 53, 1613–1624.
  35. Bernal, J. Thyroid hormone regulated genes in cerebral cortex development. J. Endocrinol. 2017, 232, R83–R97.
  36. Lavado-Autric, R.; Auso, E.; Garcia-Velasco, J.V.; Arufe Mdel, C.; Escobar del Rey, F.; Berbel, P.; Morreale de Escobar, G. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J. Clin. Invest. 2003, 111, 1073–1082.
  37. Miranda, A.; Sousa, N. Maternal hormonal milieu influence on fetal brain development. Brain Behav. 2018, 8, e00920.
  38. Delange, F. Neonatal screening for congenital hypothyroidism: Results and perspectives. Horm. Res. 1997, 48, 51–61.
  39. Patel, J.; Landers, K.; Li, H.; Mortimer, R.H.; Richard, K. Thyroid hormones and fetal neurological development. J. Endocrinol. 2011, 209, 1–8.
  40. Stenzel, D.; Huttner, W.B. Role of maternal thyroid hormones in the developing neocortex and during human evolution. Front. Neuroanat. 2013, 7, 19.
  41. Henrichs, J.; Ghassabian, A.; Peeters, R.P.; Tiemeier, H. Maternal hypothyroxinemia and effects on cognitive functioning in childhood: How and why? Clin. Endocrinol. 2013, 79, 152–162.
  42. Moog, N.K.; Entringer, S.; Heim, C.; Wadhwa, P.D.; Kathmann, N.; Buss, C. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience 2017, 342, 68–100.
  43. Andersen, S.L.; Laurberg, P.; Wu, C.S.; Olsen, J. Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: A Danish nationwide cohort study. BJOG 2014, 121, 1365–1374.
  44. Wood, C.E.; Keller-Wood, M. The critical importance of the fetal hypothalamus-pituitary-adrenal axis. F1000Research 2016, 5, 115.
  45. Yehuda, R.; Fairman, K.R.; Meyer, J.S. Enhanced brain cell proliferation following early adrenalectomy in rats. J. Neurochem. 1989, 53, 241–248.
  46. Balasubramanian, P.; Varde, P.A.; Abdallah, S.L.; Najjar, S.M.; MohanKumar, P.S.; MohanKumar, S.M. Differential effects of prenatal stress on metabolic programming in diet-induced obese and dietary-resistant rats. Am. J. Physiol. Endocrinol. Metab. 2015, 309, E582–E588.
  47. Towle, A.C.; Sze, P.Y.; Lauder, J.M. Cytosol glucocorticoid binding in monoaminergic cell groups. Dev. Neurosci. 1982, 5, 458–464.
  48. Murgatroyd, C.; Patchev, A.V.; Wu, Y.; Micale, V.; Bockmuhl, Y.; Fischer, D.; Holsboer, F.; Wotjak, C.T.; Almeida, O.F.; Spengler, D. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat. Neurosci. 2009, 12, 1559–1566.
  49. Vargas-Martinez, F.; Uvnas-Moberg, K.; Petersson, M.; Olausson, H.A.; Jimenez-Estrada, I. Neuropeptides as neuroprotective agents: Oxytocin a forefront developmental player in the mammalian brain. Prog. NeuroBiol. 2014, 123, 37–78.
  50. Hellstrom, I.C.; Dhir, S.K.; Diorio, J.C.; Meaney, M.J. Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone-serotonin-NGFI-A signalling cascade. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2012, 367, 2495–2510.
  51. Gore, A.C.; Martien, K.M.; Gagnidze, K.; Pfaff, D. Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism. Endocr. Rev. 2014, 35, 961–991.
  52. Krakowiak, P.; Walker, C.K.; Bremer, A.A.; Baker, A.S.; Ozonoff, S.; Hansen, R.L.; Hertz-Picciotto, I. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012, 129, e1121–e1128.
  53. Bilder, D.A.; Bakian, A.V.; Viskochil, J.; Clark, E.A.; Botts, E.L.; Smith, K.R.; Pimentel, R.; McMahon, W.M.; Coon, H. Maternal prenatal weight gain and autism spectrum disorders. Pediatrics 2013, 132, e1276–e1283.
  54. Reynolds, L.C.; Inder, T.E.; Neil, J.J.; Pineda, R.G.; Rogers, C.E. Maternal obesity and increased risk for autism and developmental delay among very pre-term infants. J. Perinatol. 2014, 34, 688–692.
  55. Paulson, J.F.; Mehta, S.H.; Sokol, R.J.; Chauhan, S.P. Large for gestational age and long-term cognitive function. Am. J. Obstet. Gynecol. 2014, 210, 343.e1–343.e4.
  56. Neggers, Y.H.; Goldenberg, R.L.; Ramey, S.L.; Cliver, S.P. Maternal prepregnancy body mass index and psychomotor development in children. Acta Obstet. Gynecol. Scand. 2003, 82, 235–240.
  57. Tanda, R.; Salsberry, P.J.; Reagan, P.B.; Fang, M.Z. The impact of prepregnancy obesity on children’s cognitive test scores. Matern. Child Health J. 2013, 17, 222–229.
  58. Huang, L.; Yu, X.; Keim, S.; Li, L.; Zhang, L.; Zhang, J. Maternal prepregnancy obesity and child neurodevelopment in the Collaborative Perinatal Project. Int. J. Epidemiol. 2014, 43, 783–792.
  59. Basatemur, E.; Gardiner, J.; Williams, C.; Melhuish, E.; Barnes, J.; Sutcliffe, A. Maternal prepregnancy BMI and child cognition: A longitudinal cohort study. Pediatrics 2013, 131, 56–63.
  60. Heikura, U.; Taanila, A.; Hartikainen, A.L.; Olsen, P.; Linna, S.L.; von Wendt, L.; Jarvelin, M.R. Variations in prenatal sociodemographic factors associated with intellectual disability: A study of the 20-year interval between two birth cohorts in northern Finland. Am. J. Epidemiol. 2008, 167, 169–177.
  61. Tanne, J.H. Maternal obesity and diabetes are linked to children’s autism and similar disorders. BMJ 2012, 344, e2768.
  62. Rodriguez, A.; Miettunen, J.; Henriksen, T.B.; Olsen, J.; Obel, C.; Taanila, A.; Ebeling, H.; Linnet, K.M.; Moilanen, I.; Jarvelin, M.R. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: Evidence from three prospective pregnancy cohorts. Int. J. Obes. 2008, 32, 550–557.
  63. Schaefer, C.A.; Brown, A.S.; Wyatt, R.J.; Kline, J.; Begg, M.D.; Bresnahan, M.A.; Susser, E.S. Maternal prepregnant body mass and risk of schizophrenia in adult offspring. Schizophr. Bull. 2000, 26, 275–286.
  64. Khandaker, G.M.; Dibben, C.R.; Jones, P.B. Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring? Obes. Rev. 2012, 13, 518–527.
  65. Ahlin, K.; Himmelmann, K.; Hagberg, G.; Kacerovsky, M.; Cobo, T.; Wennerholm, U.B.; Jacobsson, B. Non-infectious risk factors for different types of cerebral palsy in term-born babies: A population-based, case-control study. BJOG 2013, 120, 724–731.
  66. Crisham Janik, M.D.; Newman, T.B.; Cheng, Y.W.; Xing, G.; Gilbert, W.M.; Wu, Y.W. Maternal diagnosis of obesity and risk of cerebral palsy in the child. J. Pediatr. 2013, 163, 1307–1312.
  67. Pan, C.; Deroche, C.B.; Mann, J.R.; McDermott, S.; Hardin, J.W. Is prepregnancy obesity associated with risk of cerebral palsy and epilepsy in children? J. Child Neurol. 2014, 29, NP196–NP201.
  68. Calabuig-Navarro, V.; Puchowicz, M.; Glazebrook, P.; Haghiac, M.; Minium, J.; Catalano, P.; Hauguel deMouzon, S.; O’Tierney-Ginn, P. Effect of omega-3 supplementation on placental lipid metabolism in overweight and obese women. Am. J. Clin. Nutr. 2016, 103, 1064–1072.
  69. Challier, J.C.; Basu, S.; Bintein, T.; Minium, J.; Hotmire, K.; Catalano, P.M.; Hauguel-de Mouzon, S. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008, 29, 274–281.
  70. Lassance, L.; Haghiac, M.; Leahy, P.; Basu, S.; Minium, J.; Zhou, J.; Reider, M.; Catalano, P.M.; Hauguel-de Mouzon, S. Identification of early transcriptome signatures in placenta exposed to insulin and obesity. Am. J. Obstet. Gynecol. 2015, 212, 647.e1–647.e11.
  71. Burton, G.J.; Jauniaux, E. Pathophysiology of placental-derived fetal growth restriction. Am. J. Obstet. Gynecol. 2018, 218, S745–s761.
  72. Enstad, S.; Cheema, S.; Thomas, R.; Fichorova, R.N.; Martin, C.R.; O’Tierney-Ginn, P.; Wagner, C.L.; Sen, S. The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth. Eur. J. Clin. Nutr. 2021, 75, 180–188.
  73. Conroy, A.L.; McDonald, C.R.; Gamble, J.L.; Olwoch, P.; Natureeba, P.; Cohan, D.; Kamya, M.R.; Havlir, D.V.; Dorsey, G.; Kain, K.C. Altered angiogenesis as a common mechanism underlying pre-term birth, small for gestational age, and stillbirth in women living with HIV. Am. J. Obstet. Gynecol. 2017, 217, 684.e1–684.e17.
  74. Troncoso, F.; Acurio, J.; Herlitz, K.; Aguayo, C.; Bertoglia, P.; Guzman-Gutierrez, E.; Loyola, M.; Gonzalez, M.; Rezgaoui, M.; Desoye, G.; et al. Gestational diabetes mellitus is associated with increased pro-migratory activation of vascular endothelial growth factor receptor 2 and reduced expression of vascular endothelial growth factor receptor 1. PLoS ONE 2017, 12, e0182509.
  75. Regnault, T.R.; Orbus, R.J.; de Vrijer, B.; Davidsen, M.L.; Galan, H.L.; Wilkening, R.B.; Anthony, R.V. Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta 2002, 23, 132–144.
  76. Devarshi, P.P.; Grant, R.W.; Ikonte, C.J.; Hazels Mitmesser, S. Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia. Nutrients 2019, 11, 1107.
  77. Apicella, C.; Ruano, C.S.M.; Méhats, C.; Miralles, F.; Vaiman, D. The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia. Int. J. Mol. Sci. 2019, 20, 2837.
  78. Johnsen, G.M.; Basak, S.; Weedon-Fekjaer, M.S.; Staff, A.C.; Duttaroy, A.K. Docosahexaenoic acid stimulates tube formation in first trimester trophoblast cells, HTR8/SVneo. Placenta 2011, 32, 626–632.
  79. Basak, S.; Das, M.K.; Duttaroy, A.K. Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: Possible roles of cellular fatty acid-binding proteins. Life Sci. 2013, 93, 755–762.
  80. Stuart, T.J.; O’Neill, K.; Condon, D.; Sasson, I.; Sen, P.; Xia, Y.; Simmons, R.A. Diet-induced obesity alters the maternal metabolome and early placenta transcriptome and decreases placenta vascularity in the mouse. Biol. Reprod. 2018, 98, 795–809.
  81. Mohammed, S.; Qadri, S.S.Y.; Mir, I.A.; Kondapalli, N.B.; Basak, S.; Rajkumar, H. Fructooligosaccharide ameliorates high-fat induced intrauterine inflammation and improves lipid profile in the hamster offspring. J. Nutr. Biochem. 2021, 101, 108925.
  82. Song, L.; Sun, B.; Boersma, G.J.; Cordner, Z.A.; Yan, J.; Moran, T.H.; Tamashiro, K.L.K. Prenatal high-fat diet alters placental morphology, nutrient transporter expression, and mtorc1 signaling in rat. Obesity 2017, 25, 909–919.
  83. Srinivas, V.; Molangiri, A.; Mallepogu, A.; Kona, S.R.; Ibrahim, A.; Duttaroy, A.K.; Basak, S. Maternal n-3 PUFA deficiency alters uterine artery remodeling and placental epigenome in the mice. J. Nutr. Biochem. 2021, 96, 108784–108796.
  84. Duttaroy, A.K.; Basak, S. Maternal Fatty Acid Metabolism in Pregnancy and Its Consequences in the Feto-Placental Development. Front. Physiol. 2022, 12, 2576.
  85. Dutta-Roy, A.K. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. Am. J. Clin. Nutr. 2000, 71, 315S–322S.
  86. Shrestha, D.; Workalemahu, T.; Tekola-Ayele, F. Maternal dyslipidemia during early pregnancy and epigenetic ageing of the placenta. Epigenetics 2019, 14, 1030–1039.
  87. Saben, J.; Lindsey, F.; Zhong, Y.; Thakali, K.; Badger, T.M.; Andres, A.; Gomez-Acevedo, H.; Shankar, K. Maternal obesity is associated with a lipotoxic placental environment. Placenta 2014, 35, 171–177.
  88. Lager, S.; Ramirez, V.I.; Gaccioli, F.; Jang, B.; Jansson, T.; Powell, T.L. Protein expression of fatty acid transporter 2 is polarized to the trophoblast basal plasma membrane and increased in placentas from overweight/obese women. Placenta 2016, 40, 60–66.
  89. Segura, M.T.; Demmelmair, H.; Krauss-Etschmann, S.; Nathan, P.; Dehmel, S.; Padilla, M.C.; Rueda, R.; Koletzko, B.; Campoy, C. Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition. Placenta 2017, 57, 144–151.
  90. Dube, E.; Gravel, A.; Martin, C.; Desparois, G.; Moussa, I.; Ethier-Chiasson, M.; Forest, J.C.; Giguere, Y.; Masse, A.; Lafond, J. Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta. Biol. Reprod. 2012, 87, 14.
  91. Hirschmugl, B.; Desoye, G.; Catalano, P.; Klymiuk, I.; Scharnagl, H.; Payr, S.; Kitzinger, E.; Schliefsteiner, C.; Lang, U.; Wadsack, C.; et al. Maternal obesity modulates intracellular lipid turnover in the human term placenta. Int. J. Obes. 2017, 41, 317–323.
  92. Gazquez, A.; Prieto-Sanchez, M.T.; Blanco-Carnero, J.E.; Ruiz-Palacios, M.; Nieto, A.; van Harskamp, D.; Oosterink, J.E.; Schierbeek, H.; van Goudoever, J.B.; Demmelmair, H.; et al. Altered materno-fetal transfer of 13C-polyunsaturated fatty acids in obese pregnant women. Clin. Nutr. 2020, 39, 1101–1107.
  93. Laskewitz, A.; van Benthem, K.L.; Kieffer, T.E.C.; Faas, M.M.; Verkaik-Schakel, R.N.; Plosch, T.; Scherjon, S.A.; Prins, J.R. The influence of maternal obesity on macrophage subsets in the human decidua. Cell. Immunol. 2019, 336, 75–82.
  94. Nogues, P.; Dos Santos, E.; Jammes, H.; Berveiller, P.; Arnould, L.; Vialard, F.; Dieudonne, M.N. Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta. Clin. Epigenetics 2019, 11, 20.
  95. Scifres, C.M.; Chen, B.; Nelson, D.M.; Sadovsky, Y. Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts. J. Clin. Endocrinol. Metab. 2011, 96, E1083–E1091.
  96. Gauster, M.; Hiden, U.; van Poppel, M.; Frank, S.; Wadsack, C.; Hauguel-de Mouzon, S.; Desoye, G. Dysregulation of placental endothelial lipase in obese women with gestational diabetes mellitus. Diabetes 2011, 60, 2457–2464.
  97. Brass, E.; Hanson, E.; O’Tierney-Ginn, P.F. Placental oleic acid uptake is lower in male offspring of obese women. Placenta 2013, 34, 503–509.
  98. Lassance, L.; Haghiac, M.; Minium, J.; Catalano, P.; Hauguel-de Mouzon, S. Obesity-induced down-regulation of the mitochondrial translocator protein (TSPO) impairs placental steroid production. J. Clin. Endocrinol. Metab. 2015, 100, E11–E18.
  99. Herrera, E.; Ortega-Senovilla, H. Lipid metabolism during pregnancy and its implications for fetal growth. Curr. Pharm. Biotechnol. 2014, 15, 24–31.
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , ,
View Times: 496
Revisions: 2 times (View History)
Update Date: 03 Nov 2022
Video Production Service