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Spatiotemporal cellular map of the developing human reproductive tract.

Valentina Lorenzi1,2, Cecilia Icoresi-Mazzeo1, Charlotte Cassie1

  • 1Wellcome Sanger Institute, Cambridge, UK.

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Summary

This study maps the human reproductive tract's prenatal development using single-cell multi-omics. It reveals key genes and processes in sexual dimorphism and identifies fetal uterine vulnerability to endocrine disruptors.

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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.