Evidence for Almost Complete Sex-reversal in Bovine Freemartin Gonads: Formation of Seminiferous Tubule-like Structures and Transdifferentiation into Typical Testicular Cell Types
Evidence for Almost Complete Sex-reversal in Bovine Freemartin Gonads: Formation of Seminiferous Tubule-like Structures and Transdifferentiation into Typical Testicular Cell Types
复制标题
DOI：
10.1262/jrd.2012-070
复制
发表时间：
2012-12-01
影响因子：
1.8
通讯作者：
Kanai, Yoshiakira
中科院分区：
文献类型：
--
作者：
Harikae, Kyoko;Tsunekawa, Naoki;Kanai, Yoshiakira
在哺乳动物XY胎儿的性别决定过程中，SRY诱导支持细胞中的SOX 9，导致形成具有生精小管、间质间质细胞和管周肌样细胞的睾丸。同时XX个无SRY的胎儿发育成卵巢。在牛中，大多数XX小母牛出生时有一个雄性双胞胎，即所谓的自由交配，卵巢和生殖器功能丧失，具有雌雄同体的表型。有趣的是，freemartins有时发展高度雄性化的性腺与曲细精管样结构，尽管缺乏SRY。然而，在这些情况下，在每个性腺体细胞类型的雄性化程度是不清楚的。在这里，我们报告了一个罕见的情况下，freemartin日本黑牛犊几乎完全XX性逆转。对这头小牛的大体解剖分析显示，除了高度男性化的生殖器（包括蔓状丛、阴囊和泡状腺）外，还存在一对小睾丸状性腺，具有退化的附睾。组织学和免疫组化分析显示，这些雄性化的性腺定义明确的曲细精管样结构在整个性腺实质。在这些小管的上皮中，SOX 9阳性支持细胞（即，支持细胞沿着小管基部呈规则排列，并呈GDNF阳性，GDNF是精子发生的主要因子之一。3个β-HSD阳性细胞（即，间质细胞）和SMA阳性的管周肌样细胞周围的小管也确定。因此，我们首次在XX自由雌生殖腺中发现了卵巢体细胞向所有睾丸体细胞类型的转分化。这些数据有力地支持了哺乳动物性腺的卵巢体细胞具有高度性可塑性的观点。
During mammalian sex determination of XY fetuses, SRY induces SOX9 in Sertoli cells, resulting in formation of testes with seminiferous tubules, interstitial Leydig cells and peritubular myoid cells. Meanwhile XX fetuses without SRY develop ovaries. In cattle, most XX heifers born with a male twin, so-called freemartins, develop nonfunctioning ovaries and genitalia with an intersex phenotype. Interestingly, freemartins sometimes develop highly masculinized gonads with seminiferous tubule-like structures despite the absence of SRY. However, in these cases, the degree of masculinization in each gonadal somatic cell type is unclear. Here, we report a rare case of a freemartin Japanese black calf with almost complete XX sexreversal. Gross anatomical analysis of this calf revealed the presence of a pair of small testis-like gonads with rudimentary epididymides, in addition to highly masculinized genitalia including a pampiniform plexus, scrotum and vesicular gland. Histological and immunohistochemical analyses of these masculinized gonads revealed well-defined seminiferous tubule-like structures throughout the whole gonadal parenchyma. In epithelia of these tubules, SOX9-positive supporting cells (i.e., Sertoli cells) were found to be arranged regularly along the bases of tubules, and they were also positive for GDNF, one of the major factors for spermatogenesis. 3 beta-HSD-positive cells (i.e., Leydig cells) and SMA-positive peritubular myoid cells were also identified around tubules. Therefore, for the first time, we found the transdifferentiation of ovarian somatic cells into all testicular somatic cell types in the XX freemartin gonads. These data strongly support the idea of a high sexual plasticity in the ovarian somatic cells of mammalian gonads.