Cornification and classical versus nonclassical androgen receptor signaling in mouse penile/preputial development

Area of Science:

• Reproductive biology
• Developmental biology
• Molecular endocrinology

Background:

• Mouse penile development is critically dependent on androgens.
• The preputial lamina is an ectodermal structure that differentiates into penile or clitoral tissue.
• Androgen receptor (AR) signaling pathways, classical (AR-C) and nonclassical (AR-NC), mediate androgen effects.

Purpose of the Study:

• To investigate the specific roles of AR-C and AR-NC pathways in mouse penile development and preputial lamina canalization.
• To elucidate the molecular mechanisms underlying androgen-mediated genital development.

Main Methods:

• Utilized transgenic mice with pathway-selective AR mutant transgenes.
• Analyzed penile and clitoral development in wild-type, AR-C, AR-NC, and AR null mice.
• Examined the expression of keratin 10 and loricrin during preputial lamina canalization.

Main Results:

• AR-C signaling was sufficient to promote penile development and preputial lamina canalization in male mice.
• Canalization involved the upregulation of keratin 10 and loricrin, indicating epithelial cornification.
• AR-NC signaling or its absence led to clitoral development, with no significant upregulation of these cornification markers.

Conclusions:

• Classical AR signaling (AR-C) is the primary driver of male penile development and associated epithelial remodeling.
• Epithelial cornification, marked by keratin 10 and loricrin, is a key feature of AR-C-mediated penile development.
• Distinct AR signaling pathways dictate the differentiation of male versus female external genitalia.