Spermiation is a multiple-step process involving profound cellular changes in both spermatids and Sertoli cells. We have observed spermiation defects, including abnormalities in spermatid orientation, translocation and release, in mice deficient in the retinoic acid receptor alpha (RARA) and upon treatment with a pan-RAR antagonist. To elucidate the role of retinoid signaling in regulating spermiation, we first characterized the time course of appearance of spermiogenic defects in response to treatment with the pan-RAR antagonist. The results revealed that defects in spermiation are indeed among the earliest abnormalities in spermatogenesis observed upon inhibition of retinoid signaling. Using fluorescent dye-conjugated phalloidin to label the ectoplasmic specialization (ES), we showed for the first time that these defects involved improper formation of filamentous actin (F-actin) bundles in step 8–9 spermatids and a failure of the actin-surrounded spermatids to move apically to the lumen and to disassemble the ES. The aberrant F-actin organization is associated with diminished nectin-3 expression in both RARA-deficient and pan-RAR antagonist-treated testes. An abnormal localization of both tyrosinated and detyrosinated tubulins was also observed during spermatid translocation in the seminiferous epithelium in drug-treated testes. These results highlight a crucial role of RAR receptor-mediated retinoid signaling in regulating microtubules and actin dynamics in the cytoskeleton rearrangements, required for proper spermiation. This is critical to understand in light of ongoing efforts to inhibit retinoid signaling as a novel approach for male contraception and may reveal spermiation components that could also be considered as new targets for male contraception.

中文翻译：

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受维甲酸信号干扰后，精子形成过程中丝状肌动蛋白解体和顶端外质特化分解缺失†。

精子形成是一个多步骤过程，涉及精子细胞和支持细胞的深刻细胞变化。我们在缺乏视黄酸受体 α (RARA) 的小鼠和使用泛 RAR 拮抗剂治疗的小鼠中观察到精子形成缺陷，包括精子细胞定向、易位和释放异常。为了阐明类视黄醇信号在调节精子形成中的作用，我们首先描述了响应泛 RAR 拮抗剂治疗的生精缺陷出现的时间过程。结果表明，精子形成缺陷确实是在抑制类视黄醇信号时观察到的最早的精子发生异常之一。使用荧光染料缀合的鬼笔环肽标记外质特化（ES），我们首次表明，这些缺陷涉及步骤 8-9 精子细胞中丝状肌动蛋白 (F-肌动蛋白) 束的不当形成以及肌动蛋白包围的精子细胞无法向顶端移动到管腔并分解 ES。异常的 F-肌动蛋白组织与 RARA 缺陷和泛 RAR 拮抗剂治疗的睾丸中 nectin-3 表达减少有关。在药物处理的睾丸生精上皮中的精子细胞易位期间，也观察到酪氨酸化和去酪氨酸化微管蛋白的异常定位。这些结果突出了RAR受体介导的类视黄醇信号在调节细胞骨架重排中的微管和肌动蛋白动力学中的关键作用，这是正常精子形成所必需的。