Laboratory of Reproductive Biology, University Hospital of Copenhagen, Rigshospitalet, 2100 Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
Int J Mol Sci. 2022 Jul 19;23(14):7975. doi: 10.3390/ijms23147975.
Organotypic culture of human fetal testis has achieved fertilization-competent spermatids followed by blastocysts development. This study focuses on whether the organotypic culture of testicular tissue from infant boys with cryptorchidism could support the development of spermatogonia and somatic cells. Frozen-thawed tissues were cultured in two different media, with or without retinoic acid (RA), for 60 days and evaluated by tissue morphology and immunostaining using germ and somatic cell markers. During the 60-day culture, spermatocytes stained by boule-like RNA-binding protein (BOLL) were induced in biopsies cultured with RA. Increased AR expression (p < 0.001) and decreased AMH expression (p < 0.001) in Sertoli cells indicated advancement of Sertoli cell maturity. An increased number of SOX9-positive Sertoli cells (p < 0.05) was observed, while the percentage of tubules with spermatogonia was reduced (p < 0.001). More tubules with alpha-smooth muscle actin (ACTA, peritubular myoid cells (PTMCs) marker) were observed in an RA-absent medium (p = 0.02). CYP17A1/STAR-positive Leydig cells demonstrated sustained steroidogenic function. Our culture conditions support the initiation of spermatocytes and enhanced maturation of Sertoli cells and PTMCs within infant testicular tissues. This study may be a basis for future studies focusing on maintaining and increasing the number of spermatogonia and identifying different factors and hormones, further advancing in vitro spermatogenesis.
人胚睾丸器官培养已实现受精能力的精母细胞,随后发育为囊胚。本研究关注的是隐睾症男婴睾丸组织的器官培养是否能支持精原细胞和体细胞的发育。冷冻-解冻组织在两种不同的培养基中培养,一种含有视黄酸(RA),另一种不含 RA,培养 60 天,并通过组织形态学和使用生殖细胞和体细胞标志物的免疫染色进行评估。在 60 天的培养过程中,在含有 RA 的活检中诱导了 boule-like RNA-binding protein(BOLL)染色的精母细胞。Sertoli 细胞中 AR 表达增加(p < 0.001)和 AMH 表达减少(p < 0.001)表明 Sertoli 细胞成熟度提高。观察到 SOX9 阳性 Sertoli 细胞数量增加(p < 0.05),而具有精原细胞的小管比例减少(p < 0.001)。在缺乏 RA 的培养基中观察到更多具有 alpha-smooth muscle actin(ACTA,小管周围肌样细胞(PTMC)标志物)的小管(p = 0.02)。CYP17A1/STAR 阳性 Leydig 细胞显示出持续的类固醇生成功能。我们的培养条件支持精母细胞的启动以及 Sertoli 细胞和 PTMC 成熟的增强。本研究可能为未来研究提供基础,以关注维持和增加精原细胞数量,并确定不同的因素和激素,进一步推进体外精子发生。