Sex differences in allelic gene regulation in human placenta
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
Project Summary: The goals of this project are to determine how sex chromosome dosage (SCD) influences allelic gene regulation in the context of placental development and how SCD imbalance leads to impaired trophoblast differentiation and placental health and function. One fundamental difference between males and females is the sex chromosome content (46,XY and 46,XX), which causes imbalances in X/Y expression. While X chromosome inactivation (XCI) specifically silences one X chromosome in females to restore balanced expression, some genes escape XCI and thus have female-biased expression. In addition, Y-linked genes are only expressed in males. Prior to the onset of sex hormones, the effects of SCD on sex differences in autosomal gene expression and phenotypes are largely mediated by the dosage of sex-linked genes, especially X- and Y- paralogs. Notably, there is a marked effect of fetal sex on pregnancy outcomes. For example, carrying a male fetus is associated with increased risk of gestational diabetes and placental abruption, while carrying a female fetus is associated with increased risk of fetal growth restriction and preeclampsia. Allelic gene expression in males and females contributes to fetal sex differences. However, whether SCD contributes to allele-biased gene expression in placental development remains unknown. We previously showed that manipulation of X-linked gene dosage in mouse results in dysregulation of allelic gene expression. To determine the overall impact of differential SCD on allelic gene regulation and identify sex- linked candidate genes in human placental development as well as during trophoblast differentiation, we will use complementary ex vivo and in vitro approaches to leverage integrated multi-omics and functional studies. First, we will determine the effects of X- and Y-chromosome gene dosage on allelic gene regulation by single- nuclei and single cell assays performed in human 1st trimester placental tissue with varied sex chromosome content (Aim 1) and in trophoblast cell models derived from a unique collection of isogenic human induced pluripotent stem cells (hiPSCs) with different numbers of sex chromosomes (Aim 2). Second, we will investigate mechanisms controlling allelic gene expression by modulating the expression of sex-linked candidate X/Y paralogs and using allelic transcriptomic and epigenomic analyses to identify critical pathways (Aim 3). Third, functional assays will be carried out to evaluate phenotypic effects of differential SCD on trophoblast and trophoblast organoid function (Aims 2 and 3). Overall, this work will provide a comprehensive view of the effects of differential SCD on allele-specific gene regulation and on placental health and function. Results from this project will address a gap in our knowledge of the mechanisms underlying sex differences in allelic gene regulation at the fetal-maternal interface.
Grant Summary
Sex differences in allelic gene regulation in human placenta is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $565K for university, nonprofit, healthcare org. Applications are due 2031-02-28 (open). Check eligibility and apply with FindGrants.
Not quite the right fit?
Search 9,000+ open grants, or get matches ranked for your organization — free.
Focus Areas
Eligibility
How to Apply
Up to $565K
2031-02-28
- 1Confirm your organization is eligible for Sex differences in allelic gene regulation in human placenta from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Sex differences in allelic gene regulation in human placenta: Frequently Asked Questions
Who is eligible for the Sex differences in allelic gene regulation in human placenta?
Sex differences in allelic gene regulation in human placenta is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Sex differences in allelic gene regulation in human placenta provide?
Sex differences in allelic gene regulation in human placenta provides up to $565K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Sex differences in allelic gene regulation in human placenta deadline?
Applications for Sex differences in allelic gene regulation in human placenta are due 2031-02-28 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Sex differences in allelic gene regulation in human placenta?
To apply for Sex differences in allelic gene regulation in human placenta, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.