Department of Animal Sciences, University of Illinois, Urbana, IL, USA.
Biol Reprod. 2011 May;84(5):1024-32. doi: 10.1095/biolreprod.110.088559. Epub 2011 Feb 3.
Ovarian development absolutely depends on communication between somatic and germ cell components. In contrast, it is not until after birth that interactions between somatic and germ cells play an important role in testicular maturation and spermatogenesis. Previously, we discovered that Irx3 expression was localized specifically to female gonads during embryonic development; therefore, we sought to determine the function of this genetic locus in developing gonads of both sexes. The fused toes (Ft) mutant mouse is missing 1.6 Mb of chromosome 8, which includes the entire IrxB cluster (Irx3, Irx5, Irx6), Ftm, Fts, and Fto genes. Homozygote Ft mutant embryos die around embryonic day 13.5 (E13.5); therefore, to assess later development, we harvested gonads at E11.5 and transplanted them into nude mouse hosts. Our results show defects in somatic and germ cell maturation in developing gonads of both sexes. Testis development was normal initially; however, by 3-wk posttransplantation, expression of Sertoli and peritubular myoid cell markers were decreased. In many cases, gonocytes failed to migrate to structurally impaired basement membranes of seminiferous cords. Developmental abnormalities of the ovary appeared earlier and were more severe. Over time, the Ft mutant ovary formed very few primordial or primary follicles, which contained oocytes that failed to grow and were surrounded by scarce granulosa cells that expressed low levels of FOXL2. By 3 wk after transplantation, it was difficult to identify ovarian tissue in Ft mutant ovary transplants. In summary, we conclude that the Ft locus contains genes essential for somatic-germ cell interactions, without which the germ cell niche fails to mature in both sexes.
卵巢的发育完全依赖于体细胞和生殖细胞成分之间的通讯。相反，直到出生后，体细胞和生殖细胞之间的相互作用才在睾丸成熟和精子发生中发挥重要作用。此前，我们发现 Irx3 表达在胚胎发育过程中特异性定位于雌性性腺；因此，我们试图确定该遗传基因座在两性发育性腺中的功能。融合脚趾（Ft）突变小鼠缺失 8 号染色体的 1.6 Mb，其中包括整个 IrxB 簇（Irx3、Irx5、Irx6）、Ftm、Fts 和 Fto 基因。纯合子 Ft 突变胚胎在胚胎第 13.5 天（E13.5）左右死亡；因此，为了评估后期发育，我们在 E11.5 时收获性腺并将其移植到裸鼠宿主中。我们的结果表明，两性发育性腺中的体细胞和生殖细胞成熟存在缺陷。睾丸发育最初正常；然而，在移植后 3 周时，Sertoli 和小管周肌样细胞标记物的表达减少。在许多情况下，生殖细胞未能迁移到结构受损的生精小管基底膜。卵巢的发育异常出现得更早且更严重。随着时间的推移，Ft 突变体卵巢形成的原始或初级卵泡很少，其中包含未能生长的卵母细胞，并且周围是稀少的颗粒细胞，这些颗粒细胞表达低水平的 FOXL2。在移植后 3 周时，很难在 Ft 突变体卵巢移植中识别卵巢组织。总之，我们得出结论，Ft 基因座包含生殖细胞巢成熟所必需的基因，没有这些基因，生殖细胞巢在两性中都无法成熟。
