Hadziselimovic Faruk, Verkauskas Gilvydas, Stadler Michael B
Cryptorchidism Research Institute, Children's Day Care Center Liestal, Liestal, Switzerland.
Center of Children's Surgery, Orthopedics and Traumatology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Basic Clin Androl. 2021 Mar 18;31(1):6. doi: 10.1186/s12610-021-00124-w.
Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini-puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. However, the expression of these genes in prepubertal gonads has not been studied systematically, and little is known about the effect of hormone therapy on their testicular and neuronal expression levels. In this review, we interpret histological sections, data on hormone levels, and RNA profiling data from adult normal testes compared to pre-pubertal low infertility risk (LIR) and high infertility risk (HIR) patients randomly treated with surgery in combination with GnRHa or only surgery. We organize 31 target genes relevant for idiopathic hypogonadotropic hypogonadism and cryptorchidism into five classes depending on their expression levels in HIR versus LIR samples and their response to GnRHa treatment. Nescient-helix-loop-helix 2 (NHLH2) was the only gene showing a decreased mRNA level in HIR patients and an increase after GnRHa treatment. This phenomenon may reflect a broader effect of hormone treatment on gene expression in both testicular and central nervous system tissues, which could explain why the hypothalamus-pituitary-testicular axis is permanently restored by the administration of GnRHa.
隐睾症矫正手术后使用促性腺激素释放激素激动剂（GnRHa）治疗，可通过内分泌和转录作用恢复小青春期，并在大多数情况下预防成年后不育。哺乳动物中枢性低促性腺激素性腺功能减退有几个重要基因，包括许多在大脑和睾丸中都转录的基因。然而，这些基因在青春期前性腺中的表达尚未得到系统研究，激素疗法对其睾丸和神经元表达水平的影响也知之甚少。在本综述中，我们解读了组织学切片、激素水平数据以及成年正常睾丸与青春期前低不育风险（LIR）和高不育风险（HIR）患者的RNA分析数据，这些患者随机接受手术联合GnRHa治疗或仅接受手术治疗。我们根据31个与特发性低促性腺激素性腺功能减退和隐睾症相关的靶基因在HIR与LIR样本中的表达水平及其对GnRHa治疗的反应，将它们分为五类。无螺旋-环-螺旋2（NHLH2）是唯一一个在HIR患者中mRNA水平降低且在GnRHa治疗后升高的基因。这种现象可能反映了激素治疗对睾丸和中枢神经系统组织中基因表达的更广泛影响，这可以解释为什么GnRHa给药能使下丘脑-垂体-睾丸轴永久恢复。
