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Published on: October 13, 2018
Developmental basis of sexually dimorphic digit ratios
1Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology and Department of Biology, University of Florida, Gainesville, FL 32610, USA.
Summary
The digit ratio (2D:4D) in mice is determined by the balance of androgen and estrogen signaling during development. This hormonal influence creates a lifelong signature of prenatal endocrine exposure, impacting adult health.
Area of Science:
- Endocrinology
- Developmental Biology
- Genetics
Background:
- Sexually dimorphic digit proportions, specifically the second-to-fourth digit (2D:4D) ratio, are observed in humans and correlate with various conditions.
- While studies suggest a link between digit ratios and prenatal androgen exposure, the underlying developmental mechanisms remain unclear.
Purpose of the Study:
- To elucidate the developmental mechanism controlling sexually dimorphic digit development and the 2D:4D ratio.
- To investigate the roles of androgen and estrogen signaling in regulating digit growth and proportions.
Main Methods:
- Utilized a mouse model to study digit development.
- Manipulated androgen receptor (AR) and estrogen receptor alpha (ER-α) activity in developing digits.
- Analyzed gene expression networks controlling chondrocyte proliferation.
Main Results:
- The 2D:4D ratio in mice is controlled by the balance of androgen and estrogen signaling during a specific developmental window.
- Differential activity of AR and ER-α in digit 2 versus digit 4 influences digit growth.
- Androgen and estrogen differentially regulate gene networks, leading to sex-specific digit 4 growth.
Conclusions:
- The 2D:4D ratio is a lifelong marker of prenatal hormonal exposure, influenced by the interplay of androgen and estrogen.
- Identified molecular dimorphisms in limb buds contributing to sex differences in digit development.
- The 2D:4D ratio may serve as an indicator of disrupted endocrine signaling during fetal development and potential links to adult diseases.
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