NGF Rescues Spermatogenesis in Azoospermic Mice
NGF Rescues Spermatogenesis in Azoospermic Mice
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NGF 拯救无精子小鼠的精子发生
DOI：
10.1007/s43032-021-00511-8
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发表时间：
2021-03-16
影响因子：
2.9
通讯作者：
Wang, Yulong
中科院分区：
文献类型：
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作者：
Luo, Jiao;Yang, Yan;Wang, Yulong
神经生长因子（NGF）在调节下丘脑-垂体-性腺（HPG）轴中发挥着重要作用。然而，NGF 对精子发生的影响仍不清楚。本研究旨在评估 NGF 鼻腔递送对无精子小鼠精子发生的潜在应用。我们建立了单次腹腔（i.p.）注射白消安诱导的无精症模型。通过鼻内给药递送预先封装有脂质体（25、50和100μg/kg）的NGF。白消安注射后三周，每周进行两次NGF治疗，持续8周；通过分析精子质量、睾丸和附睾组织病理学、雄激素的变化来评价精子的再生情况。此外，注射30 mg/kg白消安会导致睾丸生精小管严重萎缩，其特征是生精成分和精子丧失。经鼻给药的 NGF 可以显着上调表达减数分裂精原细胞 (Stra8) 和精母细胞 (SYCP3) 的标记物，恢复精子发生，并通过增加性激素的分泌来提高白消安治疗小鼠的精子质量。 NGF 方便、无创的鼻腔给药可能是通过激活 HPG 轴和提高雄激素来治疗精子发生的一种新的潜在疗法。该研究为NGF在生殖内分泌领域的应用开辟了新的视野。图解摘要
Nerve growth factor (NGF) plays an important role in regulating the hypothalamus-pituitary-gonadal (HPG) axis. However, the effects of NGF on spermatogenesis remain unclear. This study aimed to assess the potential application of NGF with nasal delivery on spermatogenesis in azoospermic mice. We established a model with azoospermia induced by a single intraperitoneal (i.p.) injection of busulfan. NGF pre-encapsulated with liposomes (25, 50, and 100 μg/kg) was delivered via internasal administration. Three weeks after busulfan injection, NGF treatments were performed twice a week for 8 weeks; the change of sperm quality, testis and epididymis histopathology, and androgenic hormone were analyzed to evaluate sperm regeneration. Furthermore, 30 mg/kg busulfan injection caused severe testicular atrophy of the seminiferous tubules, characterized by a loss of spermatogenic elements and sperms. NGF with nasal administration could significantly upregulate the markers expressing meiotic spermatogonia (Stra8) and spermatocytes (SYCP3), restore spermatogenesis, and improve sperm quality in busulfan-treated mice by increasing the secretion of sexual hormones. The convenient and noninvasive nasal delivery of NGF may be a new potential therapy for spermatogenesis via activating the HPG axis and elevating androgenic hormones. This study opened a new horizon for NGF application in reproductive endocrine.Graphical abstract