Leukemia Inhibitory Factor-Receptor is Dispensable for Prenatal Testis Development but is Required in Sertoli cells for Normal Spermatogenesis in Mice.

Leukemia Inhibitory Factor-Receptor is Dispensable for Prenatal Testis Development but is Required in Sertoli cells for Normal Spermatogenesis in Mice.
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白血病抑制因子受体可用于产前睾丸发育,但在Sertoli细胞中需要小鼠正常的精子发生。

DOI:
10.1038/s41598-018-30011-w
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发表时间:
2018-08-01
期刊:
影响因子:
4.6
通讯作者:
Smith LB
Smith LB
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Curley M;Milne L;Smith S;Atanassova N;Rebourcet D;Darbey A;Hadoke PWF;Wells S;Smith LB

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白血病抑制因子(LIF)是一种属于白细胞介素-6家族的多效性细胞因子,最常注意到其在维持干细胞增殖和分化之间的平衡中的作用。在啮齿类动物中,LIF在胎儿和成人睾丸中表达;认为小管周围肌样(PTM)细胞是主要的产生部位。由于它们的解剖位置,由PTM细胞产生的LIF可能作用于小管内细胞和间质细胞,分别影响精子发生和类固醇生成。事实上,白血病抑制因子受体(LIFR)在生殖细胞、支持细胞、间质细胞、PTM细胞和睾丸巨噬细胞中表达,表明通过LIFR的LIF信号传导可能是睾丸功能的关键旁分泌调节剂。然而,睾丸LIFR信号在体内的确切作用尚未确定。为此,我们产生并表征了在生殖细胞、支持细胞或两者中缺乏LIFR的小鼠的睾丸表型,以确定LIFR信号传导在睾丸发育/功能中的作用。我们的分析表明,LIFR在正常精子发生的生殖细胞中是稳定的。然而,支持细胞LIFR消融导致退行性表型,其特征在于异常生殖细胞损失、精子停滞、生精小管扩张和随后的生精小管萎缩。
Leukemia inhibitory factor (LIF), a pleiotropic cytokine belonging to the interleukin-6 family, is most often noted for its role in maintaining the balance between stem cell proliferation and differentiation. In rodents, LIF is expressed in both the fetal and adult testis; with the peritubular myoid (PTM) cells thought to be the main site of production. Given their anatomical location, LIF produced by PTM cells may act both on intratubular and interstitial cells to influence spermatogenesis and steroidogenesis respectively. Indeed, the leukemia inhibitory factor receptor (LIFR) is expressed in germ cells, Sertoli cells, Leydig cells, PTM cells and testicular macrophages, suggesting that LIF signalling via LIFR may be a key paracrine regulator of testicular function. However, a precise role(s) for testicular LIFR-signalling in vivo has not been established. To this end, we generated and characterised the testicular phenotype of mice lacking LIFR either in germ cells, Sertoli cells or both, to identify a role for LIFR-signalling in testicular development/function. Our analyses reveal that LIFR is dispensable in germ cells for normal spermatogenesis. However, Sertoli cell LIFR ablation results in a degenerative phenotype, characterised by abnormal germ cell loss, sperm stasis, seminiferous tubule distention and subsequent atrophy of the seminiferous tubules.
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