Spermatogonia migrate to the microenvironment during the establishment from gonocytes and leave it when they differentiate. However, the mechanisms underlying the regulation of spermatogonial differentiation-associated migration remain mostly unknown. In this study, we show that spermatogonial differentiation induced by retinoic acid (RA) was accompanied with increased migration ability and elevated expression of connective tissue growth factor (CTGF), a member of the CCN family. CTGF was mainly expressed in the testicular somatic cells and committed spermatogonial progenitors. Recombinant CTGF (rCTGF) promoted the spermatogonial migration and silencing of endogenous CTGF suppressed the migration of homogenous spermatogonial cell lines. Moreover, depletion of CTGF by neutralizing antibody inhibited the elevated migration ability induced by RA, suggesting both the paracrine and autocrine roles of CTGF in spermatogonial migration associated with differentiation. Finally, CTGF interacted with β1-integrin and regulated its level in spermatogonial cell lines. Together, our study provides novel insights into the regulation of spermatogonial migration by CTGF, which may shed light on the diagnosis and treatment of male infertility.

中文翻译：

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结缔组织生长因子介导与分化相关的小鼠精原细胞迁移。

精原细胞在建立过程中会从性腺细胞迁移到微环境，并在分化时离开微环境。然而，调控精原细胞分化相关迁移的基本机制仍然未知。在这项研究中，我们表明，视黄酸（RA）诱导的精原细胞分化伴随着迁移能力的增强和结缔组织生长因子（CTGF）（CCN家族成员）的表达升高。CTGF主要在睾丸体细胞和精原细胞祖细胞中表达。重组CTGF（rCTGF）促进了精原细胞的迁移，而内源性CTGF的沉默抑制了同质精原细胞系的迁移。此外，通过中和抗体消耗CTGF可以抑制RA诱导的迁移能力升高，提示CTGF在与分化相关的精原细胞迁移中的旁分泌和自分泌作用。最后，CTGF与β1-整合素相互作用并调节其在精原细胞系中的水平。总之，我们的研究为CTGF调控精原细胞迁移提供了新的见解，这可能为男性不育症的诊断和治疗提供了启示。