卵胞浆内精子注射(Intracytoplasmic sperm injection, ICSI)技术可用于男性少精、弱精、精子畸形、无精子和常规体外受精周期失败等, 克服了精子数量不足甚至直接从附睾、睾丸获取精子来治疗不育。该技术直接将单个精子注射入卵子, 因违背自然受精的生物学法则而具有很大的遗传风险。文章对ICSI精子遗传缺陷和表观遗传缺陷及其相关疾病进行综述, 可进一步认识ICSI精子遗传与表观遗传缺陷导致后代遗传风险增加的分子的机理, 文章阐述了ICSI精子有待于通过DNA甲基化、组蛋白乙酰化等表观遗传因子进行严格质量控制, 切实降低ICSI遗传及表观遗传缺陷风险的必要性。
Intracytoplasmic sperm injection (ICSI) can be applied to treat male infertility patients of oligospermia, asthenospermia, teratospermia, azoospermia and failure of the common in-vitro fertilization (IVF), which may overcome the sperm deficiency and even obtain sperms directly from percutaneous epididymal sperm aspiration (PESA) and testicular sperm extraction (TESE). As for direct injection of a single sperm into an egg, the ICSI disobeys the biological laws of natural insemination, thus leading to high genetic and epigenetic risk for patients owing to genetic and epigenetic defect of sperm. By reviewing the genetic and epigenetic defects of ICSI sperm, as well as related diseases, this article aims at understanding of the risks resulting from the genetic and epigenetic defects of ICSI sperm at a molecular mechanism level. The results show that the quality control of ICSI sperm via detecting its epigenetic factors, such as methylated DNA and acetylated histone, is essential for reducing the genetic and epigenetic risk from ICSI.
[1] Marchesi DE, Feng HL. Sperm DNA integrity from sperm to egg. J Androl, 2007, 28(4): 481–489.
[2] 朱健生, 季钢, 张玲, 洪名云, 王朝红, 姚桂东. 卵胞浆内单精子显微注射技术在男性不育症中的临床应用. 中国优生与遗传杂志, 2008, 16(9): 106–107.
[3] World Health Organization. WHO laboratory manual for examination of human semen and semen-cervical mucus in-teraction. Cambridge, Cambridge University Press, 1999.
[4] 刘德一, Gordon Baker HW. 精子功能检测与男性不育诊治的新进展. 中华男科学杂志, 2007, 13(2): 99–109.
[5] 杨建华. 辅助生殖技术中应注意的几个问题. 中国男科学杂志, 2004, 18(5): 68–69.
[6] Johnson MD. Genetic risk of intracytoplasmic sperm in-jection in the treatment of male infertility: reconunenda-tions for genetic counseling and screening. Fertil Steril, 1998, 70(3): 397–411.
[7] Cram DS. Ma K. Bhasin S, Arias J, Pandjaitan M, Chu B, Audrins P, Saunders D, Quinn F, Dekretser D, Mclachlan R. Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: ver-tical transmission of deletions and rarity of de novo dele-tions. Feriil Steril, 2000, 74(5): 909–915.
[8] Levron J. Aviram-Goldring A, Madar I, Raviv G, Barkai G, Dor J. Sperm chromosome analysis and outcome of IVF in patients with non-mosaic Klinefelter's syndrome. Fertil Steril, 2000, 74(5): 925–929.
[9] Harari O, Bourne H, Baker G, Gronow M, Johnston I. High fertilization rate with intracytoplasmic sperm injec-tion in mosatic Klinefelter' s syndrome. Fertil Steril, 1995, 63(1): 182–184.
[10] Berta PH. Chromsome Y et sterilite masculine. Andrologie, 1999, 9(3): 333–341.
[11] Akin JW, Behzadian A, Tho SPT, McDonough PG. Evi-dence for a partial deletion in the androgen receptor gene in a phenotypic male with azoospermia. Am J Obstet Gynecol, 1991, 165(6): 1891–1894.
[12] 李娟, 王克华, 张琦, 董云玲, 孟祥阁. ICSI技术治疗男性不育的遗传学风险. 国外医学计划生育学分册, 2002, 21(1): 8–10.
[13] Georgiou I, Syrrou M, Pardalidis N, Karakitisios K, Mantzavinos T, Giotitsas N, Loutradis D, Dimitriadis F, Saito M, Miyagawa I, Tzoumis P, Sylakos A, Kanakas N, Moustakareas T, Baltogiannis D, Touloupides S, Gian-nakis D, Fatouros M, Sofikitis N. Genetic and epigenetic risks of intracytoplasmic sperm injection method. Asian J Androl. 2006, 8 (6): 643–673.
[14] 杨滨, 夏欣一, 黄宇烽, 许晓风. 精子的表观遗传学研究进展. 中华男科学杂志, 2007, 13(12): 1125–1129.
[15] Nair P. As IVF becomes more common, some concerns remain. Nat Med, 2008, 14(11): 1171.
[16] Amor DJ. Genomic imprinting, small babies and assisted reproduction. Eur J Hum Genet, 2009, 17(1): 1–2.
[17] Horsthemke B, Ludwig M. Assisted reproduction: the epigenetic perspective. Hum Reprod Update, 2005, 11(5): 473–482.
[18] Ferguson-Smith AC, Surani MA. Imprinting and the epi-genetic asymmetry between parental genomes. Science, 2001, 293(5532): 1086–1089.
[19] Sofikitis N, Miyagawa I, Yamamoto Y, Loutradis D, Loutra-dis D, Mantzavinos T, Tarlatzis V. Micro- and macro-consequences of ooplasmic injections of early haploid male gametes. Hum Reprod Update, 1998, 4(3): 197–212.
[20] De Rycke M, Liebaers I, Van Steirteghem A. Epigenetic risks related to assisted reproductive technologies: risk analysis and epigenetic inheritance. Hum Reprod. 2002, 17(10): 2487–2494.
[21] Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsu-nomiya T, Sasaki H, Yaegashi N, Arima T. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet, 2007, 16(21): 2542–2551.
[22] Kanber D, Buiting K, Zeschnigk M, Ludwig M, Hor-sthemke B. Low frequency of imprinting defects in ICSI children born small for gestational age. Eur J Hum Genet, 2009, 17(1): 22–29.
[23] Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Ka-fonek DR, Brandenburg S, Wu Y, He X, Powe NR, Feinberg AP. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science, 2003, 299(5613): 1753&n
