Spatiotemporal cellular map of the developing human reproductive tract.

Area of Science:

• Developmental Biology
• Reproductive Biology
• Genomics

Background:

• The human reproductive tract's development is crucial for fertility and health.
• Disruptions in development can lead to lifelong reproductive issues.
• Existing studies often focus on individual organs, limiting comprehensive understanding.

Purpose of the Study:

• To create a comprehensive single-cell and spatial multi-omic atlas of human reproductive tract development.
• To identify regulators of sexual dimorphism and key genes in reproductive organ formation.
• To investigate the vulnerability of fetal reproductive tissues to endocrine disruptors.

Main Methods:

• Single-cell and spatial multi-omic profiling of the human reproductive tract during prenatal development.
• Integration of histological, gene expression, and chromatin accessibility data.
• Analysis of fetal-derived organoids to assess endocrine disruptor effects.

Main Results:

• Identification of novel genes involved in Müllerian duct development and penile urethralization.
• Defined transcription factors and signaling pathways in Müllerian and Wolffian duct regionalization.
• Revealed HOX gene expression patterns and early epithelial regionalization in fallopian tubes and epididymis.
• Demonstrated fetal uterine epithelium vulnerability to estrogen-mimicking endocrine disruptors.

Conclusions:

• The study provides a detailed cellular-level map of human reproductive tract regionalization and differentiation.
• Findings offer insights into the causes of developmental reproductive disorders.
• Identified potential therapeutic targets and highlighted risks from endocrine disruptors.