Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface
Open accessAbstract
As males and females share highly similar genomes, the regulation of many sexually dimorphic traits is constrained to occur through sex-biased gene regulation. There is strong evidence that human males and females differ in terms of growth and development in utero and that these divergent growth strategies appear to place males at increased risk when in sub-optimal conditions. Since the placenta is the interface of maternal-fetal exchange throughout pregnancy, these developmental differences are most likely orchestrated by differential placental function. To date, progress in this field has been hampered by a lack of genome-wide information on sex differences in placental gene expression. Therefore, our motivation in this study was to characterize sex-biased gene expression in the human placenta. We obtained gene expression data for >300 non-pathological placenta samples from 11 microarray datasets and applied mapping-based array probe re-annotation and inverse-variance meta-analysis methods which showed that >140 genes (false discovery rate (FDR) <0.05) are differentially expressed between male and female placentae. A majority of these genes (>60%) are autosomal, many of which are involved in high-level regulatory processes such as gene transcription, cell growth and proliferation and hormonal function. Of particular interest, we detected higher female expression from all seven genes in the LHB-CGB cluster, which includes genes involved in placental development, the maintenance of pregnancy and maternal immune tolerance of the conceptus. These results demonstrate that sex-biased gene expression in the normal human placenta occurs across the genome and includes genes that are central to growth, development and the maintenance of pregnancy.
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Placentas associated with female fetuses tend to have higher expression of genes involved in immune regulation, endocrine functions, and placental growth, while those from males have more inflammatory profiles.
“Placentas associated with female fetuses tend to have higher expression of genes involved in immune regulation, endocrine functions and placental growth (71, 512), whilst those from males have more inflammatory profiles (136).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [71]
Genes encoding components of the mTOR and protein translation pathways are amongst the most sexually dimorphically expressed genes in the placenta.
“Genes encoding components of the mTOR and protein translation pathways are amongst the most sexually dimorphically expressed genes in the placenta (71).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [71]
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- Authors
- Buckberry, S., Bianco-Miotto, T., Bent, S. J., Dekker, G. A., & Roberts, C. T.
- Affiliations
- The University of Adelaide (AU)
- Lyell McEwin Hospital (AU)
- Corresponding author
- Roberts, C. T.
- Venue
- Molecular Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-27
- Volume
- 20
- Issue
- 8
- Pages
- 810-819
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- PMC
- PMC4106635
- OpenAlex
- W2147185833
- Cited by
- 186
- References
- 67
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 17 · 2023: 31 · 2022: 12 · 2021: 21 · 2020: 22 · 2019: 7 · 2018: 13 · 2017: 14 · 2016: 12 · 2015: 15
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Molecular Human Reproduction (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- South Australian Health and Medical Research Institute
- Medical Research Council
- National Health and Medical Research Council (1020749)
- Cancer Council South Australia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- sex-biased gene expression, human placenta, maternal-fetal interface, sex differences, placental gene expression, pregnancy maintenance, maternal-fetal immune tolerance, placental development
- MeSH terms
- Female, Humans, Male, Placenta, Pregnancy, Sex Chromosomes, Fetal Development, Transcriptome
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