端粒是真核生物染色体末端的多功能特异性DNA-蛋白结构,覆盖在染色体末端,保护基因组的稳定性。端粒在减数分裂过程中起到了十分重要的作用,协助染色体配对、联会、同源重组和分离。精子中的端粒可能在精子的受精能力和胚胎发育中起到重要作用。近年来,端粒与生殖的相关性研究成为一个新的热点,但精子端粒与男性不育间的相关性并不明确。本文采用实时荧光定量PCR方法检测中国特发性男性不育人群(126例)和正常可育男性人群(138例)的精子相对端粒长度,结果发现,特发性男性不育病例的精子平均相对端粒长度(2.894±0.115)低于正常对照组(4.016±0.603),差异具有统计学意义(P=5.097×10-5);并且精子相对端粒长度与精子密度、精子总数和精子活力都有显著的相关性：精子数量较多和/或精子活力较高,精子相对端粒长度较长。研究结果提示,在中国人群中,精子端粒长度与特发性男性不育具有相关性,精子的端粒长度可能影响精子发生和精子的功能,精子端粒的缩短导致精子数目及活力的降低从而导致男性不育。
刘舒媛,张昌军,彭海英,黄小琴,孙浩,林克勤,黄铠,褚嘉祐,杨昭庆
. 精子端粒长度与特发性男性不育相关[J]. 遗传, 2015
, 37(11)
: 1137
-1142
.
DOI: 10.16288/j.yczz.15-267
Telomeres are evolutionary conserved, multifunctional DNA-protein complexes located at the ends of eukaryotic chromosomes. Telomeres maintain chromosome stability and genome integrity and also play an important role in meiosis which aid in synapsis, homologous recombination, and segregation. Sperm telomere has been reported to play an important role in fertilization and embryo development. Nowadays, the association between telomere and reproduction is one of the major areas of interest, however whether sperm telomere associated with male infertility is not clear. In this study, in order to find out the association between Chinese idiopathic infertility and sperm telomere length, we analyzed the difference of sperm telomere length between idiopathic infertile men and normal fertile men, as well as the correlations between sperm telomere length and human semen characteristics. We analyzed 126 Chinese idiopathic infertile men and 138 normal fertile men for sperm telomere length by using quantitative PCR. We found that the relative sperm mean telomere length of infertile men was significantly shorter than that of fertile men (2.894±0.115 vs. 4.016±0.603, P=5.097×10-5). Both sperm count and semen progressive motility are related with telomere length. Our results suggest that sperm telomere length is associated with idiopathic male infertility of China and we proposed the possibility that shorter telomeres in sperm chromosome will reduce spermatogenesis and sperm functions, which finally affected the fertility of male.
[1] Singh K, Jaiswal D. Human male infertility: a complex multifactorial phenotype. Reprod Sci , 2011, 18(5): 418- 425.
[2] 阮健, 杜卫东. 男性不育与基因缺陷. 遗传, 2010, 32(5): 411-422.
[3] Poongothai J, Gopenath TS, Manonayaki S. Genetics of human male infertility. Singapore Med J , 2009, 50(4): 336-347.
[4] Rodríguez S, Goyanes V, Segrelles E, Blasco M, Gosálvez J, Fernández JL. Critically short telomeres are associated with sperm DNA fragmentation. Fertil Steril , 2005, 84(4): 843-845.
[5] Liu L, Blasco MA, Trimarchi JR, Keefe DL. An essential role for functional telomeres in mouse germ cells during fertilization and early development. Dev Biol , 2002, 249(1): 74-84.
[6] Keefe DL, Franco S, Liu L, Trimarchi J, Cao BN, Weitzen S, Agarwal S, Blasco MA. Telomere length predicts embryo fragmentation after in vitro fertilization in women-toward a telomere theory of reproductive aging in women. Am J Obstet Gynecol , 2005, 192(4): 1256-1260.
[7] Thilagavathi J, Venkatesh S, Dada R. Telomere length in reproduction. Andrologia , 2013, 45(5): 289-304.
[8] Campbell PJ. Telomeres and cancer: from crisis to stability to crisis to stability. Cell , 2012, 148(4): 633-635.
[9] Thilagavathi J, Kumar M, Mishra SS, Venkatesh S, Kumar R, Dada R. Analysis of sperm telomere length in men with idiopathic infertility. Arch Gynecol Obstet , 2013, 287(4): 803-807.
[10] Ferlin A, Rampazzo E, Rocca MS, Keppel S, Frigo AC, De Rossi A, Foresta C. In young men sperm telomere length is related to sperm number and parental age. Hum Reprod , 2013, 28(12): 3370-3376.
[11] Esteves SC, Zini A, Aziz N, Alvarez JG, Sabanegh ES, Jr., Agarwal A. Critical appraisal of World Health Organization's new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology , 2012, 79(1): 16-22.
[12] Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res , 2002, 30(10): e47.
[13] O'Callaghan NJ, Dhillon VS, Thomas P, Fenech M. A quantitative real-time PCR method for absolute telomere length. BioTechniques , 2008, 44(6): 807-809.
[14] Hemann MT, Rudolph KL, Strong MA, DePinho RA, Chin L, Greider CW. Telomere dysfunction triggers developmentally regulated germ cell apoptosis. Mol Biol Cell , 2001, 12(7): 2023-2030.
[15] Ferlin A, Foresta C. New genetic markers for male infertility. Curr Opin Obstet Gynecol , 2014, 26(3): 193-198.
[16] 刘静宇, 代小华, 曾宪录, 张传善, 郝水, 宋运淳. 男性育性障碍与联会复合体异常的关系. 遗传, 2005, 27(5): 819-827.
[17] Moskovtsev SI, Willis J, White J, Mullen JBM. Disruption of telomere-telomere interactions associated with DNA damage in human spermatozoa. Syst Biol Reprod Med , 2010, 56(6): 407-412.
[18] Evenson DP, Wixon R. Clinical aspects of sperm DNA fragmentation detection and male infertility. Theriogenology , 2006, 65(5): 979-991.
