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The placenta and neurodevelopment: sex differences in prenatal vulnerability
Open accessAbstract
Prenatal insults, such as maternal stress, are associated with an increased neurodevelopmental disease risk and impact males significantly more than females, including increased rates of autism, mental retardation, stuttering, dyslexia, and attention deficit/hyperactivity disorder (ADHD). Sex differences in the placenta, which begin with sex chromosomes, are likely to produce sex-specific transplacental signals to the developing brain. Our studies and others have identified X-linked genes that are expressed at higher levels in the female placenta. Through a genome-wide screen after maternal stress in mice, we identified the X-linked gene O-linked N-acetylglucosamine transferase (OGT) and demonstrated its causality in neurodevelopmental programming producing a male-specific stress phenotype. Elucidating the sex-specific molecular mechanisms involved in transplacental signals that impact brain development is key to understanding the sex bias in neurodevelopmental disorders and is expected to yield novel insight into disease risk and resilience.
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“In many studies, male offspring appear to be the most strongly affected. Interestingly, they often present with what is known as a dysmasculinized phenotype (i.e., with behaviors and gene expression patterns most commonly seen in females) (Bale 2016).”
From Prenatal developmental origins of future psychopathology: mechanisms and pathways (2019) · cites this paper as Bale 2016
In the citing paper
“In one elegant model in mice based on the X-linked gene OGT (O-linked N-acetylglucosamine transferase), male placentas with typically lower levels of OGT are poised for epigenetic alterations that appear to produce robust transcriptional responses to maternal prenatal stress that result in increased stress sensitivity as adults (Bale 2016).”
From Prenatal developmental origins of future psychopathology: mechanisms and pathways (2019) · cites this paper as Bale 2016
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Cites
Geschwind, N. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060060019009 · Cited by 1,773
Geschwind, N. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060050026008 · Cited by 1,452
Placental development: Lessons from mouse mutants
Rossant, J., & Cross, J. C. (2001) · Nature Reviews Genetics · doi:10.1038/35080570 · Cited by 1,299
Sex-Specific Programming of Offspring Emotionality after Stress Early in Pregnancy
Mueller, B. R., & Bale, T. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1424-08.2008 · Cited by 988
Self-citationEarly Life Programming and Neurodevelopmental Disorders
Bale, T. L., Baram, T. Z., Brown, A. S., Goldstein, J. M., Insel, T. R., McCarthy, M. M., Nemeroff, C. B., Reyes, T. M., Simerly, R. B., Susser, E. S., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.028 · Cited by 961
Self-citationOwens, P. C., Smith, R., Brinsmead, M. W., Hall, C., Foureur, M. J., Hurt, D., Lovelock, M., Chan, E.-C., Cubis, J., & Lewin, T. J. (1987) · Life Sciences · doi:10.1016/0024-3205(87)90603-5 · Cited by 958
Review: Sex and the human placenta: Mediating differential strategies of fetal growth and survival
Clifton, V. L. (2010) · Placenta · doi:10.1016/j.placenta.2009.11.010 · Cited by 868
Wadhwa, P. D., Sandman, C. A., Porto, M., Dunkel-Schetter, C., & Garite, T. J. (1993) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(93)90016-c · Cited by 794
Why are autism spectrum conditions more prevalent in males?
Baron-Cohen, S., Lombardo, M. V., Auyeung, B., Ashwin, E., Chakrabarti, B., & Knickmeyer, R. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001081 · Cited by 754
Seckl, J. R., & Holmes, M. C. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0515 · Cited by 754
Flagged first, then by citations
Research works printed but not linked: 8
- Sandman CA., 2013, J Psychosom Res., 75, 327, 10.1016/j.jpsychores.2013.07.009 · DOI · Paper page
- Gabory A., 2013, Biol Sex Differ., 4, 5, 10.1186/2042-6410-4-5 · DOI · Paper page
- Howerton CL., 2014, Proc Natl Acad Sci U S A., 111, 9639, 10.1073/pnas.1401203111 · DOI
- Howerton CL., 2013, Proc Natl Acad Sci USA., 110, 5169, 10.1073/pnas.1300065110 · DOI
- Mao J., 2010, Proc Natl Acad Sci U S A., 107, 5557, 10.1073/pnas.1000440107 · DOI · Paper page
- Nugent BM., 2015, Front Neuroendocrinol., 39, 28, 10.1016/j.yfrne.2015.09.001 · DOI · Paper page
- Bronson SL., 2016, Neuropsychopharmacology., 41, 207, 10.1038/npp.2015.231 · DOI
- Nyirenda MJ., 1998, Int J Mol Med., 2, 607
Cited by
Sorted by citations
Items 101–200 of 250
Nonprotein-coding RNAs in Fetal Alcohol Spectrum Disorders
Mahnke, A. H., Salem, N. A., Tseng, A. M., Chung, D. D., & Miranda, R. C. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.024 · Cited by 17
Stressful Newborn Memories: Pre-Conceptual, In Utero, and Postnatal Events
Papadopoulou, Z. L., Vlaikou, A., Theodoridou, D., Markopoulos, G. S., Tsoni, K., Agakidou, E., Drosou‐Agakidou, V., Turck, C. W., Filiou, M. D., & Syrrou, M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00220 · Cited by 19
“In humans, genetic background, age, sex, type, frequency, and duration of the stressor and developmental stage have been suggested to be important factors that shape individual stress response (123).”
BackgroundBrambilla, M., Perrone, S., Shulhai, A.-M., Ponzi, D., Paterlini, S., Pisani, F., Rollo, D., Pelosi, A., Street, M. E., & Palanza, P. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106028 · Cited by 16
“…exposure in a variety of physiological processes provided possible explanations for such a sex-biased vulnerability: during fetal development gene expression and the ratio of nervous system maturation processes are greater and faster in females than males (Bale, 2016; Rosenfeld, 2015).”
Knickmeyer, R. C., & Hooper, S. R. (2019) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31679 · Cited by 16
“rier between the maternal and fetal compartments (Bale, 2016).”
BackgroundKelly, A. C., Kramer, A. W., Rosario, F. J., Powell, T. L., & Jansson, T. (2020) · Clinical Science · doi:10.1042/cs20201050 · Cited by 15
“Recent clinical and animal experimental evidence suggests that many neuropsychiatric diseases, such as schizophrenia (9-11), autism spectrum disorder (12,13), attention deficit/hyperactivity disorder (ADHD) and depression (14), also originate in utero (15-17).”
BackgroundInfluentialSarkar, A., Balogun, K. A., Lenis, M. S. G., Acosta, S., Mount, H. T. J., & Serghides, L. (2020) · PLoS ONE · doi:10.1371/journal.pone.0242513 · Cited by 16
“Given that male placentas are more responsive to changes in the maternal environment, such as maternal exposure to drugs [47], maternal ART may have impacted the male fetuses differently from the females.”
BackgroundDevelopmental transcriptomic patterns can be altered by transgenic overexpression of Uty
Rock, K. D., Folts, L. M., Zierden, H. C., Marx-Rattner, R., Leu, N. A., Nugent, B. M., & Bale, T. L. (2023) · Scientific Reports · doi:10.1038/s41598-023-47977-x · Cited by 15
“We recognize the importance of utilizing site-specific overexpression and knockout models in future studies to probe if deletion of Uty results in loss of a proposed functions in XY males.”
Self-citationStrawn, M., Moraes, J. G. N., Safranski, T. J., & Behura, S. K. (2021) · Cells · doi:10.3390/cells10092439 · Cited by 16
White, M., & Connor, K. L. (2020) · Nutrients · doi:10.3390/nu12113375 · Cited by 14
Guma, E., & Chakravarty, M. M. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.04.012 · Cited by 14
Utility of Small Animal Models of Developmental Programming
Reynolds, C. M., & Vickers, M. H. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7614-0_8 · Cited by 14
Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner
Duffy, K. A., Sammel, M. D., Johnson, R. L., Kim, D. R., Wang, E. Y., Ewing, G., Hantsoo, L. V., Kornfield, S. L., Bale, T. L., & Epperson, C. N. (2023) · Biology of Sex Differences · doi:10.1186/s13293-023-00492-0 · Cited by 13
“The underlying mechanism for these effects may be stress hormone disruption of testosterone production during important early developmental stages of sex differentiation [67].”
BackgroundSelf-citationCzamara, D., Dieckmann, L., Lahti‐Pulkkinen, M., Cruceanu, C., Henrich, W., Plagemann, A., Räikkönen, K., Braun, T., Binder, E. B., Lahti, J. M. T., et al. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05208-0 · Cited by 15
“Furthermore, sex-differences in the placenta are likely to be also involved in how the placental development is associated with fetal brain development [64].”
BackgroundBoots, A., Thomason, M. E., Espinoza‐Heredia, C., Pruitt, P. J., Damoiseaux, J. S., Roseboom, T. J., & de Rooij, S. R. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.01.003 · Cited by 15
“Presumably, this is due to the faster growth rate of male fetuses in utero and the protective effects of the female placenta against maternal perturbations during pregnancy (Bale, 2016).”
BackgroundInfluentialHair cortisol levels in pregnancy as a possible determinant of fetal sex: a longitudinal study
Romero González, B., Puertas González, J. A., González Pérez, R., Davila, M., & Peralta Ramírez, M. I. (2020) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 13
Srividhya, D., Korlimarla, A., Ravikumar, G., Snijesh, V. P., Kaku, S. M., & Visweswariah, A. M. (2022) · Birth Defects Research · doi:10.1002/bdr2.2119 · Cited by 15
“…by using epigenetic profiles and histopathological changes in the placenta may provide a clue in identifying early biomarkers for NDDs. Additionally, the placenta is known to reflect the genetics of fetal sex as it shows sex-specific responses while programming brain development (Bale, 2016).”
BackgroundTrifunović, S. L., Šošić‐Jurjević, B., Ristić, N., Nestorović, N. M., Filipović, B. R., Stevanović, I. D., Begović-Kuprešanin, V., & Manojlović‐Stojanoski, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010540 · Cited by 13
“Therefore, it seems logical to speculate that the hereby demonstrated changes in placentas contributed directly to the observed immediate adverse effects on fetal development and the long-term impact evident in offspring of both sexes [3,4].”
BackgroundResultInfluentialWu, M., Wang, L., Liu, Y., Bi, J., Liu, Q., Chen, K., Li, Y., Xia, W., Xu, S., Zhou, A., et al. (2021) · European Journal of Pediatrics · doi:10.1007/s00431-021-04152-6 · Cited by 11
Prenatal Stress Induces Translational Disruption Associated with Myelination Deficits
Crombie, G. K., Palliser, H. K., Shaw, J. C., Hanley, B. A., Moloney, R. A., & Hirst, J. J. (2023) · Developmental Neuroscience · doi:10.1159/000530282 · Cited by 12
“There are sex-speci fi c gene and protein expression patterns in the placenta [31, 32], which may be particularly vulnerable to stress in late-gestation [33].”
BackgroundSex differences in placenta-derived markers and later autistic traits in children
Tsompanidis, A., Blanken, L. M. E., Broere-Brown, Z. A., van Rijn, B. B., Baron‐Cohen, S., & Tiemeier, H. W. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02552-w · Cited by 14
“However, it has not yet been examined if sex differences in these placenta-derived markers are associated with sex differences in neurodevelopmental outcomes and particularly in the number of autistic traits later in children [33].”
BackgroundThe impact of placental genomic risk for schizophrenia and birth asphyxia on brain development
Wortinger, L. A., Shadrin, A. A., Szabó, A., Nerland, S., Smelror, R. E., Jørgensen, K. N., Barth, C., Andreou, D., Thoresen, M., Andreassen, O. A., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02639-4 · Cited by 12
Legault, L., Dupas, T., Breton‐Larrivée, M., Filion-Bienvenue, F., Lemieux, A., Langford‐Avelar, A., & McGraw, S. (2024) · Environment International · doi:10.1016/j.envint.2024.109014 · Cited by 12
Su, Q., Zhang, H., Dang, S., Yao, D., Shao, S., Zhu, Z., & Li, H. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.06.030 · Cited by 12
Androgens Upregulate Pathogen-Induced Placental Innate Immune Response
Vancolen, S. Y., Ayash, T. A., Segura, M., Allard, M., Robaire, B., & Sébire, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094978 · Cited by 11
“Importantly, CP and ASD are more frequent in males, with a skewed sex ratio of 4:1 [8,9].”
BackgroundHiscox, L. V., Fairchild, G. F., Donald, K. A., Groenewold, N. A., Koen, N., Roos, A., Narr, K. L., Lawrence, M., Hoffman, N., Wedderburn, C. J., et al. (2022) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2023.101210 · Cited by 14
“…biological mechanisms that can help explain how an infant ’ s biological sex may modify the effect of IPV on brain structure and connectivity, with sex chromosomes in the placenta likely to produce sex-specific transplacental signals to the developing brain (Bale, 2016; Carpenter et al., 2017).”
Christians, J. K., & Reue, K. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1304050 · Cited by 11
“This leads to the prediction that, where sex differences are due to escape from XCI, males should be more affected by early-life environment, as is the case with the effects of prenatal stress mediated by Ogt (64, 67).”
BackgroundInfluentialChen, E. Y., da Cruz, R. S., Nascimento, A., Joshi, M., Pereira, D. G., Dominguez, O., Fernandes, G., Smith, M., Paiva, S. P. C., & de Assis, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-58176-7 · Cited by 11
“Animal models show that maternal exposure to benzene or stress leads to sex-specific transcriptional changes in placentas 42,43 while paternal obesity leads to placenta hypoxia in female placentas 9 .”
BackgroundPaul, E. N., Shubitidze, S., Rahim, R., Rucker, I., Valin, L., Apostle, S., Pospisilik, J. A., Racicot, K. E., & Smith, A. L. (2023) · Placenta · doi:10.1016/j.placenta.2023.08.005 · Cited by 12
Hair cortisol levels in pregnancy as a possible determinant of fetal sex: a longitudinal study
Romero-Gonzalez, B., Puertas-Gonzalez, J. A., Gonzalez-Perez, R., Davila, M., & Peralta-Ramirez, M. I. (2021) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174420001300 · Cited by 20
“For example, it has been shown that Y fetuses mature more slowly than X fetuses 44 ; they tend to present pregnancy complications and preterm birth 17,45 – 47 ; and at birth, they are more likely to have shorter telomeres 48,49 .”
Liu, H., Liu, Y., Huang, K., Yan, S., Hao, J., Zhu, P., Tao, F., & Shao, S. (2021) · BMC Pediatrics · doi:10.1186/s12887-021-02938-z · Cited by 12
“Thirdly, since the genderspecific mechanism from the glucocorticoid signaling pathway in placenta has been well-documented [10, 14, 21, 22, 45, 46], our data may be more accurate compared to prior studies which have used fetal saliva or blooding of cortisol.”
BackgroundResultRegional skull translocator protein elevation in autistic adults detected by PET-MRI
Tseng, C.-E. J., Guma, E., McDougle, C. J., Hooker, J. M., & Zürcher, N. R. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.02.002 · Cited by 8
“Several rodent studies have examined the effects of this risk factor on exposed offspring and identified some sex-specific alteration in behavior, neuroanatomy (Sal-Sarria et al., 2024), and placental function (Bale, 2016; Osman et al., 2024).”
Li, W., Zhao, J., Ni, M., Zhang, Q., Shen, Q., Li, H., Tang, Z., Yao, D., Wang, T., Qi, S., et al. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.02.006 · Cited by 9
Hilberdink, C. E., van Zuiden, M., Olff, M., Roseboom, T. J., & de Rooij, S. R. (2023) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174423000181 · Cited by 10
Pull, K., Folk, R. W., Kang, J., Jackson, S., Gusek, B., Esfandiarei, M., & Jadavji, N. M. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00502.2023 · Cited by 9
Sautreuil, C., Lecointre, M., Dalmasso, J., Lebon, A., Leuillier, M., Janin, F., Lecuyer, M., Bekri, S., Marret, S., Laquerrière, A., et al. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1294746 · Cited by 10
“Interestingly, the placenta could contribute to these sex-related behavioral troubles (Bale, 2016).”
BackgroundAlterations to Placental Glucocorticoid Receptor Expression with Alcohol Consumption
Young, S. L., Saif, Z., Meakin, A. S., McMaster, E. S., Hayes, N., Gallo, L. A., Reid, N., Moritz, K. M., & Clifton, V. L. (2021) · Reproductive Sciences · doi:10.1007/s43032-020-00413-1 · Cited by 9
“The placenta plays a key role in media t ing fe ta l growth and neurodevelopment, and perturbations have been identified for some pregnancy complications, such as asthma [13, 14].”
BackgroundTeng, Y., Li, P., Yang, M., Yan, H., Yan, S., Xu, Y., Tao, F., & Huang, K. (2022) · Thyroid · doi:10.1089/thy.2022.0044 · Cited by 8
“13 Placentas may cause ‘‘gender dimorphism’’ due to the different effects of sex hormones or sex chromosomes, 14 which transmit sex-specific placental signals to the developing brain and cause different sex-related neurodevelopmental trajectories.”
Sex differences in gene regulatory networks during mid-gestational brain development
de Toledo, V. H. C., Feltrin, A. S., Barbosa, A. D. L., Tahira, A. C., & Brentani, H. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.955607 · Cited by 12
“During fetal brain development, sex differences might emerge from the gene regulatory effects of the interplay between gonadal hormones, sex chromosomes and sex specific responsiveness to environmental factors, which collectively might contribute to higher vulnerability in male pregnancies by affecting growth and surv…”
BackgroundNotario-Barandiarán, L., Coto, S. D., Jimenez-Redondo, N., Guxens, M., Vrijheid, M., Andiarena, A., Irizar, A., Galán, I. R., Fernández‐Somoano, A., Llop, S., et al. (2023) · Exposure and Health · doi:10.1007/s12403-023-00610-8 · Cited by 8
“Apart from genetics, the observed differences in the neurodevelopmental outcomes due to metal exposure may be due to the slower brain development in males than in females, which increases the period of vulnerability to the toxic effects of metals (Bale 2016).”
Liu, Y., Zhang, M., Wang, Y., Lu, M., Wang, X., Tang, C., Li, H., Gan, H., Tong, J., Gao, H. J., et al. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.5c08732 · Cited by 8
Sex-based disparities in DNA methylation and gene expression in late-gestation mouse placentas
Legault, L., Breton‐Larrivée, M., Langford‐Avelar, A., Lemieux, A., & McGraw, S. (2024) · Biology of Sex Differences · doi:10.1186/s13293-023-00577-w · Cited by 8
“D DNA methylation levels of DMRs present on the X chromosome at both E10.”
BackgroundDenizli, M., Ropa, J. P., Beasley, L. N., Ghosh, J., DeVanna, K., Spice, T., Haneline, L. S., Capitano, M. L., & Kua, K. L. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102008 · Cited by 8
“One theory suggests the placenta of male fetuses is more reactive to maternal stress, while another proposes decreased expression of X-linked methylation genes in males leads to a more responsive chromatin state [34,40,41].”
BackgroundBiggar, E., Thomas, R. E., Lave, M. L., Bhattad, G. J., Rajakumar, N., & Renaud, S. J. (2025) · Placenta · doi:10.1016/j.placenta.2025.03.001 · Cited by 7
Sex differences in the programming of stress resilience
Morrison, K. E., Epperson, C. N., & Bale, T. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813983-7.00006-9 · Cited by 7
Self-citationAdvancing research on early autism through an integrated risk and resilience perspective
Stallworthy, I. C., & Masten, A. S. (2022) · Development and Psychopathology · doi:10.1017/s0954579421001437 · Cited by 7
“In the general population, males are four to eight times more likely than females to have a neurodevelopmental disorder (Bale, 2016).”
BackgroundHipwell, A. E., Fu, H., Tung, I., Stiller, A., & Keenan, K. E. (2023) · Frontiers in Reproductive Health · doi:10.3389/frph.2022.1007788 · Cited by 7
“Frontiers in Reproductive Health 10 consistent with prenatal stress studies that have highlighted male vulnerability (31, 32, 78, 79).”
BackgroundCleaver, P., & Non, A. L. (2024) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.22043 · Cited by 6
Wang, J., Jiang, N., Liu, F., Wang, C., & Zhou, W. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108761 · Cited by 6
Cheng, J., Jin, H., Zhang, Y., Ren, J., Huang, K., Tong, J., Gan, H., Lv, J., Wang, Q. M., Tao, F., et al. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123450 · Cited by 6
Intralitter Variability Influences the Developmental Impact of Valproic Acid Exposure in CD‐1 Mice
Brown, L. T. L., Cull, M. E., Xue, L., & Winn, L. M. (2025) · Journal of Applied Toxicology · doi:10.1002/jat.4860 · Cited by 6
Prenatal Maternal Bereavement and Its Association With Intellectual Disability in the Offspring
Su, X., Yu, Y., Meng, L., Duan, T., Zhao, Y., László, K. D., Valdimarsdóttir, U. A., Hua, J., & Li, J. (2021) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000990 · Cited by 5
“We hypothesized that the risk of ID after the prenatal stress may vary according to the timing of exposure (19), the mother’s relationship to the deceased (20), the relative’s cause of death (21), and sex of the child (22).”
BackgroundStructural and functional cerebellar impairment in the progeny of preeclamptic rat mothers
Valencia, M., Torres, E., Muñoz, F., & García, T. (2023) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-023-01503-8 · Cited by 6
“Therefore, it is known that the placenta is sexually very dimorphic and that it could be part of the origin of the differences in the alterations found [5, 27] and that the brain has been identified as structurally sexually dimorphic and vascularly dimorphic [38].”
Scarborough, J., Iachizzi, M., Schalbetter, S. M., Müller, F., Weber‐Stadlbauer, U., & Richetto, J. (2024) · Neurobiology of Stress · doi:10.1016/j.ynstr.2024.100614 · Cited by 6
“Indeed, pioneering work conducted by the Bale group demonstrated that placental sex is one of the main drivers of the functional response of the placenta to in-utero perturbations (Bale, 2016).”
A head start: The relationship of placental factors to craniofacial and brain development
Carver, A. J., Dunnwald, M., & Stevens, H. E. (2025) · Developmental Dynamics · doi:10.1002/dvdy.70018 · Cited by 6
Carver, A. J., Fairbairn, F. M., Taylor, R. J., Boggarapu, S., Kamau, N. R., Gajmer, A., & Stevens, H. E. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115453 · Cited by 9
Shared genetic factors, fetal programming, and the transmission of depression
Lugo-Candelas, C. I., Monk, C. E., Duarte, C. S., Lee, S., & Posner, J. E. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(18)30356-0 · Cited by 5
“10 It is thus possible that by examining male and female offspring together, some effects went undetected.”
BackgroundTiny Babies Grow Up: The Long-Term Effects of Extremely Low Birth Weight
Mathewson, K. J., Burack, J. A., Saigal, S., & Schmidt, L. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-60159-1_16 · Cited by 7
Deady, C., FitzGerald, J., Kara, N. Z., Mazzocchi, M., O'Mahony, A., Ionescu, M.-I., Shanahan, R., Kelly, S., Crispie, F., Cotter, P. D., et al. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101065 · Cited by 4
“Studies have revealed that the male placenta responds and adapts to prenatal stressors differently in comparison to the female placenta (Bale, 2016; P ´ erez-Cerezales et al., 2018).”
Ayash, T. A., Allard, M., Chevin, M., & Sébire, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111393 · Cited by 4
“The impact of chorioamnionitis on neurodevelopment results in a wide variety of manifestations depending on the severity and timing of the brain injury, with some children experiencing mild developmental delays and others facing lifelong challenges [3,7,12].”
BackgroundMohammadzadeh, P., Jepsen, J. R. M., Lemvigh, C. K., Rosenberg, J. B., Hernández‐Lorca, M., Sevelsted, A., Vinding, R., Vahman, N., Horner, D., Sørensen, M. E., et al. (2025) · Psychological Medicine · doi:10.1017/s0033291725000674 · Cited by 4
“BRIEF-2 and SDQ outcomes at age 10 BRIEF-2 GEC and SDQ outcomes were highly correlated (Supplementary Table S12).”
Hao, X., Guo, Y., Lu, J., Zhu, L., Yan, S., Tao, F., & Huang, K. (2024) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-024-02411-z · Cited by 4
“These differences might be related to the sexual dimorphic programming of placental development, which produced sex-specific placental signals to the developing brain [34].”
Díaz‐Pons, A., Castaño-Castaño, S., de la Foz, V. O., & Ayesa‐Arriola, R. (2025) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-025-02837-z · Cited by 3
“Bale et al., (2016) suggested that sex differences in placental responses to early prenatal stress – specifically, differences in transcriptional repression and regulation – may contribute to this increased male susceptibility [37].”
Chen, R., Liu, W., Wu, F., Ye, X., Wang, X., Zheng, Y., Tan, W., Ding, R., Liu, M., Gao, Y., et al. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1536042 · Cited by 5
Mancuso, C., Bacquet, M., Benjamin, L., Leroy, F., & Dehaene‐Lambertz, G. (2025) · Brain Structure and Function · doi:10.1007/s00429-025-02979-5 · Cited by 3
“…al. 2019) although this view has been challenged by a recent meta-analysis (Christians et al. 2023 ) Although it remains difficult to disentangle cultural from biological influences, several studies have reported early sex-related differences in brain maturation and stress reactivity (Bale 2016).”
Hernández, M. H., Santos, E. D., Rodriguez, Y., Ferchaud‐Roucher, V., Rousseau‐Ralliard, D., Frambourg, A., Berveiller, P., Vialard, F., Couturier‐Tarrade, A., & Dieudonné, M. (2025) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2025.112640 · Cited by 4
Paliokha, R., Viñas-Noguera, M., Bukatová, S., Grinchii, D., Gaburjáková, J., Gaburjáková, M., Özbaşak, H., Dekhtiarenko, R., Khoury, T., Lacinová, Ľ., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03161-3 · Cited by 3
“This effect was observed in female, but not in male offspring.”
Beraldo, E. O., Inkster, A. M., Peñaherrera, M. S., Price, E. M., Schuetz, J. M., Portales-Casamar, É., Kildea, S. V., Vaillancourt, C., King, S., & Robinson, W. P. (2025) · Placenta · doi:10.1016/j.placenta.2025.09.003 · Cited by 3
“It remains unclear if cell composition sex differences are associated with the differences we see in male and female vulnerability to exposures and prevalence of placental complications [14,65,66], but future investigation is warrented.”
The association between female newborn and placental malaria infection: A case-control study
Ahmed, I. A. M., Elmugabil, A., Adam, I., & Almohaimeed, A. (2023) · Placenta · doi:10.1016/j.placenta.2023.05.006 · Cited by 2
Transcriptomic comparison of in vitro models of the human placentaPreprint
Lapehn, S., Nair, S., Firsick, E. J., MacDonald, J. W., Thoreson, C., Litch, J. A., Bush, N. R., Kadam, L., Girard, S., Myatt, L., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.14.598695 · Cited by 3
“Physiological differences in the placenta by fetal sex include differences in placental weight to birthweight ratio indicating potential differences in placental reserve capacity by fetal sex [47,48] as well as sex-specific transplacental signals to the brain [49].”
BackgroundDNA methylation in the placenta and household socioeconomic status: the SPAH study
Beraldo, E. O., Borders, A. E. B., Inkster, A. M., Ernst, L. M., Freedman, A. A., Kim, J., Keenan‐Devlin, L. S., Peñaherrera, M. S., Robinson, W. P., & Miller, G. E. (2026) · Clinical Epigenetics · doi:10.1186/s13148-026-02136-7 · Cited by 2
“Subsequent studies should explore whether differences in cell composition contribute to differences in XX and XY vulnerability to in utero exposures and prevalence of placental complications [29, 61, 76].”
Environmental risk factors for neurodevelopmental disorders: Evidence from twin studies
Stephenson, G. L., & Craig, J. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821514-2.00037-4 · Cited by 2
Kelm, M. R., Schuetze, P. A., & Eiden, R. D. (2024) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2024.107399 · Cited by 2
Prenatal Programming in the Fetus and Placenta
Scorza, P., Doyle, C., & Monk, C. E. (2021) · Springer eBooks · doi:10.1007/978-3-030-60159-1_4 · Cited by 2
Merced‐Nieves, F. M., Eitenbichler, S., Goldson, B., Zhang, X., Klein, D. N., Enlow, M. B., Curtin, P. C. P., Wright, R. O., & Wright, R. J. (2023) · Child Development · doi:10.1111/cdev.13997 · Cited by 2
Yazıcı, İ. P. (2020) · Çocuk ve Gençlik Ruh Sağlığı Dergisi / Turkish Journal of Child and Adolescent Mental Health · doi:10.4274/tjcamh.galenos.2020.46220 · Cited by 4
Levitan, R. D., Zhang, C. X. W., Knight, J. A., Hung, R. J., Wade, M., Finegold, K. E., Ameis, S. H., Bertoni, K., Wong, J., Murphy, K. E., et al. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116430 · Cited by 2
“Several authors have highlighted the importance of these differences in establishing sex-specific vulnerabilities to mental disorders (Davis and Pfaff, 2014; Bale, 2016; Moriarty et al., 2019).”
Estrogen regulates placental immune processes in non-human primates
Khoshravesh, S., Liu, A., Shukla, V., Babischkin, J. S., Aberdeen, G. W., Pepe, G. J., Albrecht, E. D., Lei, J., & Burd, I. D. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf112 · Cited by 1
Sex-specific influences of prenatal inflammation on offspring psychological symptoms in late midlife
Smith, E., Pike, M. R., Kring, A. M., Cogan, A. B., Breen, E. C., Cohn, B. A., Cirillo, P. M., Krigbaum, N. Y., Olino, T. M., Alloy, L. B., et al. (2026) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2026.107791 · Cited by 1
Maternal sleep deprivation and developmental programming of brain aging trajectories in offspring
Sontakke, S., Wankhede, N. L., Yadav, A., Taksande, B. G., Aglawe, M. M., Rahangdale, S. R., Umekar, M., & Kale, M. (2026) · Biogerontology · doi:10.1007/s10522-026-10458-5 · Cited by 2
“Although the underlying mechanisms remain incompletely understood, differences in fetal hormonal milieu, placental function, immune signaling, and stress responsiveness may contribute to sex-dependent susceptibility (Clifton 2010; Bronson and Bale 2015; Bale 2016).”
Intersection of schizophrenia genetics and placental complications
McCarthy, M. M. (2018) · Nature Medicine · doi:10.1038/s41591-018-0066-y · Cited by 1
Babineau, V., Jolicoeur‐Martineau, A., Székely, E., Green, C. G., Sassi, R. B., Gaudreau, H., Levitan, R. D., Lydon, J. E., Steiner, M. S., O’Donnell, K. J., et al. (2023) · Developmental Psychobiology · doi:10.1002/dev.22395 · Cited by 1
“Our findings of biological sex differences can in part be interpreted alongside the evi-dencethatmalesexposedtomaternalstressinuteroareatgreaterrisk ofdevelopingneurodevelopmentaldisorders(Bale,2016).”
Prenatal opioid exposure and the early life epigenome: results from ECHO
Schrott, R., Garrison‐Desany, H. M., Avalos, L. A., Breton, C. V., Dabelea, D., Derefinko, K. J., Dunlop, A. L., Fang, F., Gaylord, A., Grant, T. L., et al. (2024) · Journal of Substance Use · doi:10.1080/14659891.2024.2356569 · Cited by 1
Hercus, J. C., Rubio, D. A. S., Nieto, M. E. O., Keum, C., Wang, Q., Macdonald, J. A., Scott, J. S., Lucas, E. R. J., & Christians, J. K. (2025) · Molecular Human Reproduction · doi:10.1093/molehr/gaaf015 · Cited by 1
“…the chromosomal complement of the fetus and thus has a sex (Clifton, 2010; Gabory et al. , 2013; Rosenfeld, 2015; Tarrade et al. , 2015; Bronson and Bale, 2016; Burton et al. , 2016; Cheong et al. , 2016; Kalisch-Smith et al. , 2017; Dearden et al. , 2018; P � erez-Cerezales et al. , 2018; Meakin…”
Prenatal famine exposure and late-life functional brain network connectivity: A longitudinal study
Boots, A., Damoiseaux, J. S., Jung, Y., Wiegersma, A. M., Schrantee, A., Boucherie, D. E., Roseboom, T. J., & de Rooij, S. R. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149859 · Cited by 1
“There are known sex-differences in prenatal vulnerability, with the male fetus being more vulnerable to prenatal exposures (Bale 2016).”
Relationship between perinatal period problems and developmental delay in children aged 4-24 months
Kaviani, M., Ranjbaran, Z., & Janghorban, R. (2019) · AFMN Biomedicine · doi:10.5937/afmnai2004337k · Cited by 1
“X-linked genes that are expressed in female placental cells place the placenta in a position that is less vulnerable to the surrounding environment, and this provides a protective condition for the development of the brain (18).”
BackgroundCascalho, A. C. C., Foroozandeh, J., Rous, S., Vizcaíno, N. M., Gallego, S. F., & Goodchild, R. E. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.18.997247 · Cited by 1
“This difference arises in utero suggesting it relates to pregnancy differences between species; potentially the multiple pregnancies of mice where male and female embryos differentially compete for resources (Bale, 2016).”
BackgroundInfluentialSex differences in placental markers and later autistic traitsPreprint
Tiemeier, H. W., Tsompanidis, A., Blanken, L. M. E., Broere-Brown, Z. A., van Rijn, B. B., & Baron‐Cohen, S. (2022) · Research Square · doi:10.21203/rs.3.rs-1716102/v1 · Cited by 1
Mancuso, C., Bacquet, M., Benjamin, L., Leroy, F., & Dehaene‐Lambertz, G. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.07.592881 · Cited by 1
“…Hirnstein et al., 2019 but see the recent metanalysis of Christians et al., 2023) Although it is intrinsically difficult to disentangle cultural from biological factors, some studies report early biological differences in brain maturation and response to stress in males and females (Bale, 2016).”
BackgroundInflammation and immune-mediated neurobehavioral alterations : a critical role for microglia
Lacabanne, C. (2018) · theses.fr (ABES) · doi:10.70675/41a4e2a3zdbb7z4aa0z899dz9553bb07954b · Cited by 1
Mediation and Moderation of Intergenerational Epigenetic Effects of Trauma
Pilkay, S. R. (2017)
Zoubovsky, S. P., Williams, M. T., Hoseus, S., Tumukuntala, S., Riesenberg, A. N., Schulkin, J. A., Vorhees, C. V., Campbell, K., Lim, H., & Muglia, L. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.20.106674
“Several studies have shown distinct sex differences in epigenetic regulators and methylation patterns of placental tissues, providing a plausible mechanism by which females may adopt placental adaptive responses to environmental insults (Bale, 2016; Gallou-Kabani et al., 2010; Nugent et al., 2018).”
BackgroundInterrogating placental function in pregnancies affected by prenatal depression
Sumption, L. A. (2020) · ORCA Online Research @Cardiff (Cardiff University)
Zoubovsky, S. P., Wilder, A., & Muglia, L. J. (2021) · Journal of Visualized Experiments · doi:10.3791/62464
Liu, H., Liu, Y., Huang, K., Yan, S., Hao, J., Zhu, P., Tao, F., & Shao, S. (2021) · Research Square · doi:10.21203/rs.3.rs-686489/v2
Liu, H., Liu, Y., Huang, K., Yan, S., Hao, J., Zhu, P., Tao, F., & Shao, S. (2021) · Research Square · doi:10.21203/rs.3.rs-686489/v1
The Aftermath of Crime: Indirect Exposure to Homicides, Maternal Stress, and Newborns’ HealthPreprint
Moscoso, B. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4160203
Role of Gender and Neurodevelopmental Disabilities
Greydanus, D. E., Patel, D. R., & Merrick, J. (2023) · Springer eBooks · doi:10.1007/978-3-031-20792-1_41
Legault, L., Breton‐Larrivée, M., Langford‐Avelar, A., Lemieux, A., & McGraw, S. (2024) · Figshare · doi:10.6084/m9.figshare.24953178
Mobbing Maternal en las Instituciones de Salud
Palacios, M. T. D., & Martínez, J. A. M. (2025) · Religación · doi:10.46652/rgn.v10i44.1368
Metadata
- Authors
- Bale, T. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bale, Tracy L.
- ORCID
- Bale, Tracy L.
- Venue
- Dialogues in Clinical Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2016-12-31
- Volume
- 18
- Issue
- 4
- Pages
- 459-464
- ISSN
- 1294-8322 (ISSN-L)
- 1958-5969
- PMC
- PMC5286731
- OpenAlex
- W2988356887
- Cited by
- 236
- References
- 86
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 23 · 2023: 35 · 2022: 30 · 2021: 32 · 2020: 20 · 2019: 17 · 2018: 20 · 2017: 7
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Dialogues in Clinical Neuroscience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh091258-05)
- National Institute of Mental Health (P50MH099910, R37MH108286, R33MH104184, R01 MH-091258, R01MH087597)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- placenta, sex differences, brain development, prenatal stress, maternal stress, neurodevelopmental disorders, autism spectrum disorder, attention deficit hyperactivity disorder, X-linked genes, O-GlcNAc transferase, sex bias
- MeSH terms
- Animals, Female, Humans, Male, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics, Stress, Physiological, Stress, Psychological, Neurodevelopmental Disorders
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