Absence of colony-stimulating factor-1 in osteopetrotic (csfm(op)/csfm(op)) mice results in male fertility defects

Absence of colony-stimulating factor-1 in osteopetrotic (csfm(op)/csfm(op)) mice results in male fertility defects
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DOI:
10.1095/biolreprod55.2.310
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发表时间:
1996-08-01
影响因子:
3.6
通讯作者:
Pollard, JW
Pollard, JW
中科院分区:
生物学2区
文献类型:
--
作者:
Cohen, PE;Chisholm, O;Pollard, JW

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先前的研究表明,单核吞噬细胞生长因子、集落刺激因子-1(CSF-1)在女性生殖中具有重要作用。骨石症 (csfm(op)/csfm(op)) 小鼠的交配实验表明,CSF-1 基因具有失活突变,雄性和雌性都存在生殖缺陷。在本研究中,我们发现雄性 csfm(op)/csfm(op) 小鼠的循环睾酮 (T) 浓度比野生型小鼠低七倍,睾丸内 T 浓度显着降低。 T浓度的降低与交配能力的降低和存活精子数量的减少有关。雄性 csfm(op)/csfm(op) 小鼠在成年后使用循环 T 或在整个出生后期间使用循环 CSF-1 进行重建,完全恢复了存活精子数量并显着恢复了性行为。这些观察结果,加上间质细胞与睾丸巨噬细胞的密切关联以及这些巨噬细胞在调节间质细胞类固醇生成中的拟议功能,表明 CSF-1 调节的睾丸巨噬细胞在男性生殖中发挥重要作用。
Previous studies have shown that the mononuclear phagocyte growth factor, colony-stimulating factor-1 (CSF-1), has an important role in female reproduction. Mating experiments with osteopetrotic (csfm(op)/csfm(op)) mice, which possess an inactivating mutation in the CSF-1 gene, suggested that there are male, as well as female, reproductive defects. In the present study, we have shown that male csfm(op)/csfm(op) mice have a sevenfold lower concentration of circulating testosterone (T) and a significantly lower intratesticular T concentration than wild-type mice. These lowered T concentrations were associated with a reduction in mating capability and a reduction in the number of viable sperm. Reconstitution of male csfm(op)/csfm(op) mice with either circulating T in the adult or circulating CSF-1 throughout the postnatal period completely restored viable sperm numbers and significantly restored sexual behavior. These observations, coupled with the close association of Leydig cells with testicular macrophages and the proposed function of these macrophages in the regulation of Leydig cell steroidogenesis, suggest that CSF-1-regulated testicular macrophages play an important role in male reproduction.