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Sexually dimorphic expression of Mafb regulates masculinization of the embryonic urethral formation.


ABSTRACT: Masculinization of external genitalia is an essential process in the formation of the male reproductive system. Prominent characteristics of this masculinization are the organ size and the sexual differentiation of the urethra. Although androgen is a pivotal inducer of the masculinization, the regulatory mechanism under the control of androgen is still unknown. Here, we address this longstanding question about how androgen induces masculinization of the embryonic external genitalia through the identification of the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (Mafb) gene. Mafb is expressed prominently in the mesenchyme of male genital tubercle (GT), the anlage of external genitalia. MAFB expression is rarely detected in the mesenchyme of female GTs. However, exposure to exogenous androgen induces its mesenchymal expression in female GTs. Furthermore, MAFB expression is prominently down-regulated in male GTs of androgen receptor (Ar) KO mice, indicating that AR signaling is necessary for its expression. It is revealed that Mafb KO male GTs exhibit defective embryonic urethral formation, giving insight into the common human congenital anomaly hypospadias. However, the size of Mafb KO male GTs is similar with that of wild-type males. Moreover, androgen treatment fails to induce urethral masculinization of the GTs in Mafb KO mice. The current results provide evidence that Mafb is an androgen-inducible, sexually dimorphic regulator of embryonic urethral masculinization.

SUBMITTER: Suzuki K 

PROVIDER: S-EPMC4246345 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Sexually dimorphic expression of Mafb regulates masculinization of the embryonic urethral formation.

Suzuki Kentaro K   Numata Tomokazu T   Suzuki Hiroko H   Raga Dennis Diana DD   Ipulan Lerrie Ann LA   Yokoyama Chikako C   Matsushita Shoko S   Hamada Michito M   Nakagata Naomi N   Nishinakamura Ryuichi R   Kume Shoen S   Takahashi Satoru S   Yamada Gen G  

Proceedings of the National Academy of Sciences of the United States of America 20141031 46


Masculinization of external genitalia is an essential process in the formation of the male reproductive system. Prominent characteristics of this masculinization are the organ size and the sexual differentiation of the urethra. Although androgen is a pivotal inducer of the masculinization, the regulatory mechanism under the control of androgen is still unknown. Here, we address this longstanding question about how androgen induces masculinization of the embryonic external genitalia through the i  ...[more]

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