Lambeth Luke S, Ayers Katie, Cutting Andrew D, Doran Timothy J, Sinclair Andrew H, Smith Craig A
Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
Murdoch Childrens Research Institute, Melbourne, Victoria, Australia Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Biol Reprod. 2015 Dec;93(6):138. doi: 10.1095/biolreprod.115.131664. Epub 2015 Oct 28.
In mammals, the primary role of anti-Müllerian hormone (AMH) during development is the regression of Müllerian ducts in males. These structures otherwise develop into fallopian tubes, oviducts, and upper vagina, as in females. This highly conserved function is retained in birds and is supported by the high levels of AMH expression in developing testes. In mammals, AMH expression is controlled partly by the transcription factor, SOX9. However, in the chicken, AMH mRNA expression precedes that of SOX9 , leading to the view that AMH may lie upstream of SOX9 and play a more central role in avian testicular development. To help define the role of AMH in chicken gonad development, we suppressed AMH expression in chicken embryos using RNA interference. In males, AMH knockdown did not affect the expression of key testis pathway genes, and testis cords developed normally. However, a reduction in the size of the mesonephros and gonads was observed, a phenotype that was evident in both sexes. This growth defect occurred as a result of the reduced proliferative capacity of the cells of these tissues, and male gonads also had a significant reduction in germ cell numbers. These data suggest that although AMH does not directly contribute to testicular or ovarian differentiation, it is required in a sex-independent manner for proper cell proliferation and urogenital system growth.
在哺乳动物中,抗苗勒管激素(AMH)在发育过程中的主要作用是使雄性苗勒管退化。否则,这些结构会像在雌性中一样发育成输卵管、卵巢管和上阴道。这种高度保守的功能在鸟类中也存在,并且发育中的睾丸中高水平的AMH表达也支持了这一点。在哺乳动物中,AMH的表达部分受转录因子SOX9控制。然而,在鸡中,AMH mRNA的表达先于SOX9,这导致了一种观点,即AMH可能位于SOX9的上游,并在禽类睾丸发育中发挥更核心的作用。为了帮助确定AMH在鸡性腺发育中的作用,我们使用RNA干扰抑制了鸡胚胎中AMH的表达。在雄性中,AMH基因敲低并不影响关键睾丸通路基因的表达,睾丸索正常发育。然而,观察到中肾和性腺的大小减小,这种表型在两性中都很明显。这种生长缺陷是由于这些组织细胞的增殖能力降低所致,雄性性腺中的生殖细胞数量也显著减少。这些数据表明,虽然AMH并不直接参与睾丸或卵巢的分化,但它以性别独立的方式对正常的细胞增殖和泌尿生殖系统生长是必需的。