Identification, Expression, and Regulation of Anti-Mullerian Hormone Type-II Receptor in the Embryonic Chicken Gonad

Identification, Expression, and Regulation of Anti-Mullerian Hormone Type-II Receptor in the Embryonic Chicken Gonad
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DOI:
10.1095/biolreprod.113.116491
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发表时间:
2014-05-01
影响因子:
3.6
通讯作者:
Smith, Craig A.
Smith, Craig A.
中科院分区:
生物学2区
文献类型:
--
作者:
Cutting, Andrew D.;Ayers, Katie;Smith, Craig A.

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抗苗勒管激素(AMH)信号是脊椎动物泌尿生殖系统正常发育所必需的。在雄性哺乳动物中,AMH负责使苗勒管退化,苗勒管否则发育成输卵管、输卵管和雌性生殖道的上阴道。这种作用在高等脊椎动物中是高度保守的。然而,AMH是缺乏穆勒管的鱼类睾丸发育所需的,这意味着AMH信号在其他脊椎动物中具有更广泛的作用。AMH通过两个丝氨酸/苏氨酸激酶受体进行信号传导。主要AMH受体,AMH受体II型(AMHR 2),募集I型受体,其在细胞内转导信号。为了加深对AMH信号传导机制及其在性腺性别分化中的潜在作用的理解,我们克隆了鸡AMHR 2 cDNA,并检测了其在性腺性别分化过程中的表达谱。AMHR 2在两性的性腺和苗勒管中表达,但在性腺性别分化开始后在雄性中表达更强。在睾丸中,AMHR 2蛋白与AMH共定位在睾丸索的支持细胞内。AMHR 2蛋白表达在雌激素合成抑制剂法倔唑处理的雌性胚胎中上调。相反,敲低睾丸关键基因DMRT 1导致AMHR 2在发育中的雄性生精索中的表达中断。这些结果表明AMHR 2在鸡胚胎睾丸分化过程中受到发育调控。AMH信号可能是重要的性腺分化,除了苗勒管退化的鸟类。
Anti-Mullerian hormone (AMH) signaling is required for proper development of the urogenital system in vertebrates. In male mammals, AMH is responsible for regressing the Mullerian ducts, which otherwise develop into the fallopian tubes, oviducts, and upper vagina of the female reproductive tract. This role is highly conserved across higher vertebrates. However, AMH is required for testis development in fish species that lack Mullerian ducts, implying that AMH signaling has broader roles in other vertebrates. AMH signals through two serine/threonine kinase receptors. The primary AMH receptor, AMH receptor type-II (AMHR2), recruits the type I receptor, which transduces the signal intracellularly. To enhance our understanding of AMH signaling and the potential role of AMH in gonadal sex differentiation, we cloned chicken AMHR2 cDNA and examined its expression profile during gonadal sex differentiation. AMHR2 is expressed in the gonads and Mullerian ducts of both sexes but is more strongly expressed in males after the onset of gonadal sex differentiation. In the testes, the AMHR2 protein colocalizes with AMH, within Sertoli cells of the testis cords. AMHR2 protein expression is up-regulated in female embryos treated with the estrogen synthesis inhibitor fadrozole. Conversely, knockdown of the key testis gene DMRT1 leads to disruption of AMHR2 expression in the developing seminiferous cords of males. These results indicate that AMHR2 is developmentally regulated during testicular differentiation in the chicken embryo. AMH signaling may be important for gonadal differentiation in addition to Mullerian duct regression in birds.