Department of Growth and Reproduction and International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
Andrology. 2021 Mar;9(2):618-631. doi: 10.1111/andr.12949. Epub 2020 Dec 7.
Spermatogenesis depends on stimulation by follicle-stimulating hormone (FSH) which binds to FSH receptors (FSHR) on testicular Sertoli cells. Three FSH-related single-nucleotide polymorphisms (SNPs), FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205) and FSHR 2039A>G (rs6166) affect FSH action, and have been suggested to affect testicular function, but the evidence is uncertain.
To describe the associations between the three SNPs and testicular function in a large and well-characterised cohort of men from the general population.
A cross-sectional study of 2020 Danish men unselected regarding testicular function. Outcome variables were semen parameters, reproductive hormones and testis size. Genotyping was done by competitive allele-specific quantitative PCR. Differences in genotype frequencies were tested by chi-square test and associations between genotypes and outcomes were assessed by multivariate linear regressions.
The SNPs affected serum FSH; carriers of the variant affecting FSH secretion (FSHB -211G>T) had lower FSH levels while carriers of variants affecting receptor expression (FSHR -29G>A) and receptor sensitivity (FSHR 2039A>G) had higher FSH levels. Carriers of FSHB -211G>T had lower calculated free testosterone/LH ratio. Although both FSHB -211G>T and FSHR 2039A>G were associated with smaller testis size, no clear association was detected in relation to any semen parameters, except a lower total number of morphologically normal spermatozoa in the heterozygous carriers of the FSHB -211G>T DISCUSSION AND CONCLUSION: The studied polymorphisms have only minor modulating influence on testis size and function in healthy men. We detected subtle effects of the three SNPs on FSH levels, but also effects of FSHB -211G>T on calculated free testosterone/LH ratio, compatible with altered Leydig cell function. Thus, the role of these FSH-related polymorphisms is complex and modest in men with normal testicular function, but the possible importance of FSH polymorphisms in men with impaired testicular function should be evaluated in future studies in more detail.
精子发生依赖于卵泡刺激素（FSH）的刺激，FSH 通过与睾丸支持细胞上的 FSH 受体（FSHR）结合来发挥作用。三种与 FSH 相关的单核苷酸多态性（SNP），FSHB-211G>T（rs10835638）、FSHR-29G>A（rs1394205）和 FSHR 2039A>G（rs6166），影响 FSH 的作用，并且可能影响睾丸功能，但证据并不确定。
在一个来自普通人群的大型、特征良好的男性队列中，描述这三种 SNP 与睾丸功能之间的关联。
这是一项针对 2020 名丹麦男性的横断面研究，这些男性未经选择，具有正常的睾丸功能。结局变量为精液参数、生殖激素和睾丸大小。通过竞争性等位基因特异性定量 PCR 进行基因分型。通过卡方检验检测基因型频率的差异，并通过多元线性回归评估基因型与结局之间的关系。
这些 SNP 影响血清 FSH；携带影响 FSH 分泌的变异型（FSHB-211G>T）的个体 FSH 水平较低，而携带影响受体表达（FSHR-29G>A）和受体敏感性（FSHR 2039A>G）的变异型的个体 FSH 水平较高。携带 FSHB-211G>T 的个体计算的游离睾酮/LH 比值较低。虽然 FSHB-211G>T 和 FSHR 2039A>G 均与较小的睾丸大小相关，但与任何精液参数均无明显关联，除了 FSHB-211G>T 杂合子携带者的形态正常精子总数较低外。
在所研究的健康男性中，这些多态性对睾丸大小和功能只有轻微的调节作用。我们检测到这三种 SNP 对 FSH 水平的微妙影响，但也检测到 FSHB-211G>T 对计算的游离睾酮/LH 比值的影响，提示黄体生成细胞功能改变。因此，这些与 FSH 相关的多态性在正常睾丸功能的男性中作用复杂且适度，但在睾丸功能受损的男性中，FSH 多态性的重要性应在未来的研究中更详细地评估。
