与三种呼吸系统疾病关联的男性不育症

doi:10.12280/gjszjk.20200389

摘要/Abstract

摘要：

男性不育症是一种复杂的临床综合征,任何干扰男性生殖功能的疾病都可能导致男性不育症,这使临床实践中男性不育症病因诊断变得复杂。呼吸系统上皮纤毛与男性精子鞭毛之间存在相似的超微解剖结构,纤毛和鞭毛功能障碍将影响呼吸道黏膜清除功能和精子运动。另外,某些遗传缺陷也可同时导致呼吸系统和男性生殖系统的异常。这类影响男性生育的呼吸系统疾病主要包括原发性纤毛运动障碍、囊性纤维化和Young综合征,介绍这三种疾病的主要临床特点及研究进展,并分析其呼吸系统与生殖系统临床表现之间的异同,以助于加强对这类疾病的认识。对于严重弱精子症患者,临床医生应常规询问呼吸系统病史,对于反复呼吸道感染的患者同样应关注他们的生育问题。

关键词: 不育,男（雄）性, 纤毛运动障碍, 鼻窦炎, 支气管扩张症, 卡塔格内综合征, 囊性纤维化, Young综合征

Abstract:

Male infertility is a complex clinical syndrome. Any disease that interferes with male reproductive function may lead to male infertility, which complicates the etiological diagnosis of male infertility in clinical practice. There are similar ultrastructures between the cilia of respiratory system epithelium and the flagellum of male sperm. The dysfunction of cilia and flagellum will affect the clearance function of respiratory tract mucosa and sperm movement. In addition, some of genetic defects can also lead to abnormal function of respiratory system and male reproductive system. Three kinds of respiratory diseases affecting male fertility were primary ciliary dyskinesia, cystic fibrosis and Young′s syndrome. This review introduceds the main clinical characteristics of these diseases and analyzed the differences between the clinical manifestations of respiratory system and reproductive system, which will strengthen the understanding of these diseases. It is suggested that clinicians should routinely inquire about the history of respiratory system for patients with severe asthenospermia, and about the reproductive problem for those patients with recurrent respiratory tract infection.

Key words: Infertility,male, Ciliary motility disorders, Sinusitis, Bronchiectasis, Kartagener syndrome, Cystic fibrosis, Young′s syndrome;

刘彩钊, 王家雄, 樊彩斌, 杨慎敏. 与三种呼吸系统疾病关联的男性不育症[J]. 国际生殖健康/计划生育, 2021, 40(2): 126-130.

LIU Cai-zhao, WANG Jia-xiong, FAN Cai-bin, YANG Shen-min. Male Infertility Associated with Three Kinds of Respiratory Diseases[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(2): 126-130.

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参考文献 31

[1]	Sironen A, Shoemark A, Patel M, et al. Sperm defects in primary ciliary dyskinesia and related causes of male infertility[J]. Cell Mol Life Sci, 2020,77(11):2029-2048. doi: 10.1007/s00018-019-03389-7. doi: 10.1007/s00018-019-03389-7 URL pmid: 31781811
[2]	Furlow B. Respiratory disease and fertility are linked-but why?[J]. Lancet Respir Med, 2014,2(1):28. doi: 10.1016/S2213-2600(13)70241-8. doi: 10.1016/S2213-2600(13)70241-8 URL pmid: 24461894
[3]	McCormick JP, Weeks CG, Rivers NJ, et al. Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia[J]. Int Forum Allergy Rhinol, 2019,9(12):1430-1435. doi: 10.1002/alr.22414. doi: 10.1002/alr.22414 URL pmid: 31430425
[4]	Vanaken GJ, Bassinet L, Boon M, et al. Infertility in an adult cohort with primary ciliary dyskinesia: phenotype-gene association[J]. Eur Respir J, 2017,50(5):1700314. doi: 10.1183/13993003.00314-2017. doi: 10.1183/13993003.00314-2017 URL pmid: 29122913
[5]	Horani A, Ferkol TW. Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications[J]. Chest, 2018,154(3):645-652. doi: 10.1016/j.chest.2018.05.007. doi: 10.1016/j.chest.2018.05.007 URL pmid: 29800551
[6]	Mirra V, Werner C, Santamaria F. Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies[J]. Front Pediatr, 2017,5:135. doi: 10.3389/fped.2017.00135. doi: 10.3389/fped.2017.00135 URL pmid: 28649564
[7]	Saglani S. Lung function in primary ciliary dyskinesia: breaking the myth that this is a mild disease[J]. Eur Respir J, 2018,52(2):1801365. doi: 10.1183/13993003.01365-2018. doi: 10.1183/13993003.01365-2018 URL pmid: 30139762
[8]	叶露瑶, 敬然. 精子成熟过程中鞭毛蛋白的变化[J]. 国际生殖健康/计划生育杂志, 2017,36(2):120-124. doi: 10.3969/j.issn.1674-1889.2017.02.008.
[9]	余怡, 王家雄, 杨慎敏. 精子鞭毛缺陷导致弱精子症的研究进展[J]. 中国男科学杂志, 2018,32(6):69-72. doi: 10.3969/j.issn.1008-0848.2018.06.017.
[10]	Thomas L, Bouhouche K, Whitfield M, et al. TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella[J]. Am J Hum Genet, 2020,106(2):153-169. doi: 10.1016/j.ajhg.2019.12.010. doi: 10.1016/j.ajhg.2019.12.010 URL pmid: 31978331
[11]	Ji ZY, Sha YW, Ding L, et al. Genetic factors contributing to human primary ciliary dyskinesia and male infertility[J]. Asian J Androl, 2017,19(5):515-520. doi: 10.4103/1008-682X.181227. doi: 10.4103/1008-682X.181227 URL pmid: 27270341
[12]	Halbeisen FS, Shoemark A, Barbato A, et al. Time trends in diagnostic testing for primary ciliary dyskinesia in Europe[J]. Eur Respir J, 2019,54(4):1900528. doi: 10.1183/13993003.00528-2019. doi: 10.1183/13993003.00528-2019 URL pmid: 31273043
[13]	Shoemark A, Rubbo B, Haarman E, et al. The Controversies and Difficulties of Diagnosing Primary Ciliary Dyskinesia[J]. Am J Respir Crit Care Med, 2020,201(1):120-122. doi: 10.1164/rccm.201907-1334LE. doi: 10.1164/rccm.201907-1486LE URL pmid: 31386818
[14]	Boon M, Jorissen M, Proesmans M, et al. Primary ciliary dyskinesia,an orphan disease[J]. Eur J Pediatr, 2013,172(2):151-162. doi: 10.1007/s00431-012-1785-6. doi: 10.1007/s00431-012-1785-6 URL
[15]	陈天东, 胡晨凡, 黄清洁, 等. 原发性纤毛运动障碍主要诊断方法的研究进展[J]. 中华实用诊断与治疗杂志, 2018,32(3):304-306. doi: 10.13507/j.issn.1674-3474.2018.03.030.
[16]	高立伟, 徐保平. 关注儿童囊性纤维化[J]. 中华实用儿科临床杂志, 2018,33(4):309-312. doi: 10.3760/cma.j.issn.2095-428X.2018.04.018.
[17]	Patat O, Pagin A, Siegfried A, et al. Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens[J]. Am J Hum Genet, 2016,99(2):437-442. doi: 10.1016/j.ajhg.2016.06.012. doi: 10.1016/j.ajhg.2016.06.012 URL pmid: 27476656
[18]	Regard L, Martin C, Chassagnon G, et al. Acute and chronic non-pulmonary complications in adults with cystic fibrosis[J]. Expert Rev Respir Med, 2019,13(1):23-38. doi: 10.1080/17476348.2019.1552832. doi: 10.1080/17476348.2019.1552832 URL pmid: 30472915
[19]	季新忠, 黄丽, 杜志鹏, 等. 囊性纤维化研究进展[J]. 国际呼吸杂志, 2020,40(3):235-237. doi: 10.3760/cma.j.issn.1673-436X.2020.03.015.
[20]	Yoon JC, Casella JL, Litvin M, et al. Male reproductive health in cystic fibrosis[J]. J Cyst Fibros, 2019,18(Suppl 2):S105-S110. doi: 10.1016/j.jcf.2019.08.007.
[21]	de Souza D, Faucz FR, Pereira-Ferrari L, et al. Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling[J]. Andrology, 2018,6(1):127-135. doi: 10.1111/andr.12450. doi: 10.1111/andr.12450 URL pmid: 29216686
[22]	Buchwald M, Tsui LC, Riordan JR. The search for the cystic fibrosis gene[J]. Am J Physiol, 1989,257(2 pt 1):L47-L52. doi: 10.1152/ajplung.1989.257.2.2.L47. doi: 10.1152/ajplung.1989.257.2.L47 URL pmid: 2669523
[23]	Fernandez Fernandez E, De Santi C, De Rose V, et al. CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease[J]. Expert Rev Respir Med, 2018,12(6):483-492. doi: 10.1080/17476348.2018.1475235. doi: 10.1080/17476348.2018.1475235 URL pmid: 29750581
[24]	Bai S, Du Q, Liu X, et al. The detection and significance of cystic fibrosis transmembrane conductance regulator gene promoter mutations in Chinese patients with congenital bilateral absence of the vas deferens[J]. Gene, 2018,672:64-71. doi: 10.1016/j.gene.2018.05.108. URL pmid: 29864494
[25]	Rafeeq MM, Murad H. Cystic fibrosis: current therapeutic targets and future approaches[J]. J Transl Med, 2017,15(1):84. doi: 10.1186/s12967-017-1193-9. doi: 10.1186/s12967-017-1193-9 URL pmid: 28449677
[26]	Bourke SJ, Anderson A, Briggs J, et al. Current status of fertility and family formation in men with cystic fibrosis[J]. Hum Fertil(Camb), 2019,Aug 29:1-6. doi: 10.1080/14647273.2019.1656824.
[27]	Arya AK, Beer HL, Benton J, et al. Does Young′s syndrome exist?[J]. J Laryngol Otol, 2009,123(5):477-481. doi: 10.1017/S0022215109004307. doi: 10.1017/S0022215109004307 URL pmid: 19128521
[28]	Goeminne PC, Dupont LJ. The sinusitis-infertility syndrome: Young′s saint,old devil[J]. Eur Respir J, 2010,35(3):698. doi: 10.1183/09031936.00163809. doi: 10.1183/09031936.00163809 URL pmid: 20190337
[29]	Mohammed SK, Jan A . Young Syndrome[M]. StatPearls, 2020,Aug 22.
[30]	Ozkavukcu S, Celik-Ozenci C, Konuk E, et al. Live birth after Laser Assisted Viability Assessment (LAVA) to detect pentoxifylline resistant ejaculated immotile spermatozoa during ICSI in a couple with male Kartagener′s syndrome[J]. Reprod Biol Endocrinol, 2018,16(1):10. doi: 10.1186/s12958-018-0321-6. doi: 10.1186/s12958-018-0321-6 URL pmid: 29402277
[31]	Fajac I, De Boeck K. New horizons for cystic fibrosis treatment[J]. Pharmacol Ther, 2017,170:205-211. doi: 10.1016/j.pharmthera.2016.11.009. doi: 10.1016/j.pharmthera.2016.11.009 URL pmid: 27916649

疾病	PCD	CF	Young综合征
主要临床表现	鼻窦炎、支气管扩张、中耳炎、内脏反位等	肺部感染、外分泌性胰腺功能不全、胆管阻塞、CBAVD等	梗阻性无精子症、支气管扩张、鼻窦炎等
发病年龄	10~29岁	幼年时期	年轻男性
自愈性	不可自愈	不可自愈	鼻窦炎可自愈
遗传方式	AR	AR	无
主要致病基因	DNAH5、DNAI1等	CFTR等	未知
生殖系统结构异常	无	先天性双侧输精管缺如伴附睾缺如、精囊缺如等	附睾头膨大,体尾萎缩（附睾梗阻）
纤毛超微结构	内外动力臂缺失	正常	正常
nNO浓度	显著降低	降低	正常
汗液检查	正常	氯化物升高	正常
精液量	正常	减少	正常
精浆果糖浓度	正常	明显降低	正常
精子浓度	基本正常	无精子	无精子
精子活动度	几乎为0	正常	正常

疾病	PCD	CF	Young综合征
主要临床表现	鼻窦炎、支气管扩张、中耳炎、内脏反位等	肺部感染、外分泌性胰腺功能不全、胆管阻塞、CBAVD等	梗阻性无精子症、支气管扩张、鼻窦炎等
发病年龄	10~29岁	幼年时期	年轻男性
自愈性	不可自愈	不可自愈	鼻窦炎可自愈
遗传方式	AR	AR	无
主要致病基因	DNAH5、DNAI1等	CFTR等	未知
生殖系统结构异常	无	先天性双侧输精管缺如伴附睾缺如、精囊缺如等	附睾头膨大,体尾萎缩（附睾梗阻）
纤毛超微结构	内外动力臂缺失	正常	正常
nNO浓度	显著降低	降低	正常
汗液检查	正常	氯化物升高	正常
精液量	正常	减少	正常
精浆果糖浓度	正常	明显降低	正常
精子浓度	基本正常	无精子	无精子
精子活动度	几乎为0	正常	正常