The Role of Male Sex Hormones in Placental Function and Their Association with Stillbirth and Miscarriage BIOR402
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- Subject Code :
BIOR402
- University :
others Exam Question Bank is not sponsored or endorsed by this college or university.
- Country :
Australia
Proposal Outline
Title
The Role of Male Sex Hormones in Placental Function and Their Association with Stillbirth and Miscarriage
Abstract
- Brief summary of the research problem, objectives, methodology, and expected outcomes.
- Emphasize the knowledge gap in androgen influence on placental function and pregnancy outcomes.
Introduction
3.1 Background & Rationale
- Overview of placental function and fetal development.
- The role of sex hormones, particularly androgens (testosterone, DHT) in pregnancy.
- Sex-based differences in pregnancy outcomes (higher stillbirth risk in male fetuses).
3.2 Research Problem
- Limited research on how male sex hormones affect placental health.
- Potential impact of androgen imbalances on placental dysfunction and pregnancy loss.
3.3 Research Questions & Hypothesis
- Research Questions:
- How do male sex hormones influence placental function?
- Are androgen levels altered in pregnancies affected by stillbirth or miscarriage?
- What molecular pathways are involved in androgen-mediated placental dysfunction?
- Hypothesis:
- Elevated androgens impair placental function, leading to increased pregnancy loss risk.
Literature Review
- Sexual dimorphism in placental function.
- Androgen receptor expression in the placenta.
- Association of hormone imbalances with pregnancy complications (preeclampsia, gestational diabetes, miscarriage).
- Current gaps in research and need for further investigation.
Methodology
5.1 Study Design
- Case-control study comparing:
- Cases: Stillbirth/miscarriage pregnancies.
- Controls: Normal-term pregnancies.
5.2 Sample Collection
- Placental tissue, maternal blood, and fetal cord blood collection.
- Sample preservation methods for different analyses (RNAlater, formalin, liquid nitrogen).
5.3 Hormone Quantification
- Testosterone & DHT measurement using ELISA & LC-MS.
5.4 Molecular Analysis
- RNA sequencing & single-cell RNA sequencing (scRNA-seq).
- Circular RNA profiling to explore androgen-responsive gene regulation.
- Androgen receptor (AR) expression using immunohistochemistry (IHC).
5.5 Advanced Placental Imaging
- Confocal & multiphoton microscopy for androgen receptor localization.
- 3D imaging of placental vasculature using micro-CT.
5.6 Functional Studies (In Vitro Experiments)
- Cultured placental organoids & trophoblast cells exposed to testosterone, DHT, and flutamide.
- Assessments:
- Cell viability (MTT, BrdU).
- Migration & invasion (Boyden chamber).
- Oxidative stress (ROS, mitochondrial function).
5.7 Statistical & Bioinformatics Analysis
- t-tests, ANOVA, regression models for hormone-marker correlations.
- Machine learning models for biomarker prediction.
Expected Outcomes
- Establish whether androgen levels correlate with stillbirth/miscarriage risk.
- Identify androgen-responsive pathways affecting placental function.
- Provide potential biomarkers for early pregnancy risk assessment.
Significance of Study
- Bridging a major knowledge gap in male hormone impact on placental health.
- Potential clinical applications: Early detection & intervention for high-risk pregnancies.
- Contribution to precision medicine & fetal health research.
Ethical Considerations
- Ethics approval from Flinders University & partner hospitals.
- Informed consent from all participants.
- Data privacy & confidentiality measures.
Timeline & Work Plan
- Estimated timeline with key milestones:
- Sample collection (Months 1-6)
- Laboratory analyses (Months 7-12)
- Data analysis & interpretation (Months 13-18)
- Manuscript preparation & publication (Months 19-24)
10. Budget & Funding
- Laboratory reagents & sequencing costs
- Equipment (microscopy, imaging, bioinformatics software)
- Research assistant salary & participant compensation
