Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia; Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia.
Mol Cell Endocrinol. 2019 Dec 1;498:110546. doi: 10.1016/j.mce.2019.110546. Epub 2019 Aug 15.
Heat reversibly disrupts spermatogenesis, but the effects on Sertoli cell (SC) function and inhibin/activin-related proteins are less well-defined. Adult rat testis weights decreased by 40% within 2 weeks after heat-treatment (43 °C, 15 min), due to loss of pachytene spermatocytes and round spermatids. Coincident effects were reduced SC nuclear volume at one week and >50% reduction in expression of several critical SC genes (Inha, Cld11, Gja1, Tjp1, Cldn3) by 2 weeks. Leydig cell steroidogenic enzymes, Cyp11a1, Hsd3b1, were also reduced. Activin gene expression was unaffected at this time, but expression of the activin-binding protein, follistatin (Fst), increased >2-fold. At 4-8 weeks, coincident with the recovery of spermatocytes and early spermatids, but progressive loss of elongated spermatids, most SC genes had recovered; however, testicular activin A was reduced and activin B increased. At 8 weeks, serum inhibin was decreased and, consequently, serum FSH increased. Crucially, germ cell damage was not associated with a significant inflammatory response. At 14 weeks, most testicular parameters had returned to normal, but testis weights remained slightly reduced. These data indicate that, following acute heat-treatment, expression of several key Sertoli and Leydig cell genes declined in parallel with the initial loss of meiotic germ cells, whereas activins were responsive to the subsequent loss of mature spermatids, leading to an increase in testicular activin B production relative to activin A.
热疗可使精子发生可逆性破坏，但对支持细胞（Sertoli cell，SC）功能和抑制素/激活素相关蛋白的影响尚不清楚。成年大鼠睾丸在热疗（43°C，15min）后 2 周内重量下降了 40%，这是由于精母细胞和圆形精子细胞丢失所致。同时，1 周时 SC 核体积缩小，2 周时几个关键的 SC 基因（Inha、Cld11、Gja1、Tjp1、Cldn3）的表达减少了>50%。Leydig 细胞类固醇生成酶 Cyp11a1、Hsd3b1 也减少了。此时激活素基因表达不受影响，但激活素结合蛋白 follistatin（Fst）的表达增加了>2 倍。4-8 周时，与精母细胞和早期精子细胞的恢复同时发生，但伸长的精子细胞逐渐丢失，大多数 SC 基因已经恢复；然而，睾丸激活素 A 减少，激活素 B 增加。8 周时，抑制素血清水平降低，随后 FSH 血清水平升高。至关重要的是，生殖细胞损伤与明显的炎症反应无关。14 周时，大多数睾丸参数已恢复正常，但睾丸重量仍略有降低。这些数据表明，在急性热疗后，几个关键的 Sertoli 和 Leydig 细胞基因的表达与减数分裂生殖细胞的最初丢失平行下降，而激活素对成熟精子细胞的随后丢失有反应，导致睾丸激活素 B 的产生相对于激活素 A 增加。
