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MAP3K1 regulates female reproductive tract development.

Eiki Kimura¹, Maureen Mongan¹, Bo Xiao¹

¹Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.

Disease Models & Mechanisms

|March 19, 2024

Summary

Mitogen-activated protein 3 kinase 1 (MAP3K1) is crucial for female reproductive tract development. MAP3K1 deficiency causes infertility by disrupting Müllerian duct development and WNT signaling, essential for proper formation.

Keywords:

Female reproductive tract Imperforate vagina MAP3K1 Müllerian duct WNT signaling

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Area of Science:

Reproductive biology
Developmental biology
Cell signaling

Background:

Mitogen-activated protein 3 kinase 1 (MAP3K1) has diverse cell-specific roles.
Its function in female reproductive tract (FRT) development is largely unknown.

Purpose of the Study:

To investigate the role of MAP3K1 in female reproductive tract development.
To elucidate the molecular mechanisms underlying MAP3K1's function in this process.

Main Methods:

Generated MAP3K1 kinase domain-deficient female mice.
Analyzed FRT development, Müllerian duct (MD) morphology, and WNT signaling.
Assessed Jun-N-terminal kinase (JNK) activation and cell polarity.
Utilized conditioned media assays to evaluate paracrine signaling.

Main Results:

MAP3K1 deficiency resulted in imperforate vagina, labor failure, and infertility in mice.
Defects included shunted MDs, contorted caudal vagina, and impaired vaginal-urogenital sinus fusion.
MAP3K1 is essential for JNK activation, cell polarity in MD epithelium, and WNT signaling upregulation in surrounding mesenchyme.
Reduced WNT7B ligand expression was observed in MAP3K1-deficient cells.

Conclusions:

MAP3K1 regulates female reproductive tract development, specifically MD caudal elongation and fusion.
MAP3K1 functions by inducing paracrine factors in the MD epithelium that activate WNT signaling in the mesenchyme.
This pathway is critical for normal FRT formation and reproductive success.