阴道菌群

阴道菌群(英语:Vaginal flora)或阴道微生物(vaginal microbiota)是在阴道内生长的微生物,为人类微生物群系中的一部份,由德国妇科医生艾伯特·窦特兰英语Albert Döderlein在1892年发现[1]。细菌的数量和种类可以反映女性的身体健康情形。健康女性阴道内主要的细菌是乳杆菌属[2](例如卷曲乳杆菌英语Lactobacillus crispatus),普遍认为这种细菌分泌的乳酸可以避免致病原的感染[3]

乳杆菌以及阴道的上皮组织细胞

乳杆菌

健康女性阴道内主要的细菌是乳杆菌属的细菌[2],自从窦特兰首次提到阴道中的乳杆菌起,一般都认为乳杆菌有助于维持阴道内的生态系统。已证实乳杆菌可以抑制致病微生物的生长,例如梭样类杆菌英语Bacteroides fragilis大肠杆菌阴道加德诺菌英语Gardnerella vaginali、动弯杆菌(Mobiluncus)属、淋球菌、厌氧消化链球菌(Peptostreptococcus anaerobius)、P. bivia金黄色葡萄球菌等。一般认为抑制致病微生物的作用是透过乳酸进行的[4][5][6][7]。而且乳杆菌属会附著在阴道上皮细胞,因此可以避免其他致病菌的感染以及长期生长[8]

乳杆菌可以制造乳酸,并且乳杆菌会附著在阴道上皮组织,影响其他微生物的生长,其他阴道内的拮抗作用包括产生过氧化氢(广谱抗菌剂)以及细菌素英语bacteriocin(靶特异性抗菌剂)[9][10]

产生乳酸

 
糖原是存在在阴道上皮中的糖,会分解成乳酸

一般认为低pH值是控制阴道菌群生成的主要机制。虽然乳杆菌产生的乳酸会让阴道变酸性,不过尚未证明其为阴道酸性的主要来源,目前已确定的是大部份的乳杆菌在pH < 4.5时生长得最好[11][12][13]

过氧化氢

产生过氧化氢(H2O2)是众所周知的抗菌机制[14][15][16],透过直接作用或是透过人类的骨髓过氧化酶抑制微生物成长[17][18][19]。会产生过氧化氢的乳杆菌可以使HIV-1、单纯疱疹病毒第2型(HSV-2)、阴道毛滴虫、阴道加德诺菌、P. bivia及大肠杆菌去活化。O'Hanlon[10]和Baeten[20]发现在健康女性的阴道生态系中,有96%的乳杆菌属细菌会产生H2O2(其中以詹氏乳杆菌L. jensenii和阴道乳杆菌L. vaginalis生成的比例最高)[9][21],若是有阴道细菌炎的女性,其阴道生态系中只有6%的乳杆菌属细菌会产生H2O2[17]。和上述研究一致的是,有阴道细菌炎的女性,其阴道生态系中常见的菌种L. iners[22][23],分泌H2O2的效果不佳[24][25]。制造H2O2的乳杆菌定殖在阴道也和细菌性阴道病(BV)发生率的下降有关系[26]

不过,最近由O'Hanlon等人进行的研究[27]发现宫颈阴道液和精液会阻断H2O2的活性,而且后来发现[10]体内H2O2浓度(小于100 μM)无法让受测的17种会造成细菌性阴道病的细菌(例如A. vaginae、阴道加德诺菌、Mobiluncus spp., P. bivia, Prevotella corporis, Mycoplasma hominis等)去活化,甚至是已知可提升H2O2杀菌活性的骨髓过氧化酶存在时也是如此[10]。只有超生理浓度的外源性H2O2(0.34% w/v, 100 mM)才能让上述细菌去活化,而且此浓度对乳杆菌(如卷曲乳杆菌、L. gasseri, L. iners及詹氏乳杆菌)的去活化作用反而更强。100 mM 浓度的 H2O2 是在最理想的好氧、低抗氧化条件下,乳杆菌可以生成H2O2的50倍,是平常阴道内H2O2浓度的5000倍。而且更值得注意的是,即使是浓度1 M的2O2,只要加了1%的阴道液就失去抗菌能力。可能的解释是宫颈阴道液和精液中的特定蛋白质、糖蛋白、多糖、脂质或其他物质和H2O2作用,使其失去抗菌能力。而且阴道多半是缺氧的,而乳杆菌需要氧气才能制备H2O2。{transh}}另外,在乳杆菌体内没有可以保护细菌不受H2O2毒性影响的过氧化氢酶[17][28],因此这些乳杆菌可能也会受自身分泌的H2O2所影响。相反的,在理想的厌氧生长条件下,乳杆菌在阴道内分泌的乳酸浓度可以使致病菌去活化,不会影响到乳杆菌自身[10][27]

总结来说,乳杆菌分泌的H2O2曾被认为是阴道内重要的抗菌成份[9][29],这似乎和会分泌H2O2的乳杆菌及正常阴道菌群有关,不过现今的资料无法支持H2O2在阴道抗菌作用的论点[10][27]

杀菌素

阴道的乳杆菌会产生抗菌性的肽,例如乳杆菌素(lactocin)160及crispasin等杀菌素[11],其抗菌范围从窄谱(只针对高度相关的乳酸杆菌菌种)到广谱(包括阴道加德诺菌及P. bivia)不等[6],也会产生其他类似杀菌素,但其抗菌范围更广的物质(例如由Lactobacillus salivarius subsp salivarius产生的耐热肽CRL 1328)。许多研究指出这些杀菌素在酸环境下的活性最强。

阴道的乳杆菌产生的抑制物质(包括有机酸、抗菌素及过氧化氢)是保护阴道菌群的主要因素。这些物质协同作用以保护致病菌的感染。不是所有Lactobacillus菌属的都有这三种抗菌机制,也不是所有的Lactobacillus菌株都有这三种抗菌机制[11]。绝经前妇女的Lactobacillus菌种会有所不同,例如卷曲乳杆菌(L. crispatus)、詹氏乳杆菌(L. jensenii)、惰性乳杆菌(L. iners)及加氏乳杆菌(L. gasseri),也可能有阴道乳杆菌(L. vaginalis),其评估技术有些和细菌培养有关,也有些是和细菌培养无关的技术[22][23][24][30]

阴道乳杆菌有阴道嗜性(vaginotropism)的特性,其菌毛类似配体,可以附著在阴道上皮细胞的受体上。在人体阴道中发现的Lactobacillus菌种数量有限,这可能是阴道有一些选择菌种的宿主因素、这些菌种有可以在阴道中生存的特性,也有可能两种都有[31]。不过阴道嗜性不是健康女性阴道内的乳杆菌才有的特质,像会造成细菌性阴道炎的细菌也有阴道嗜性[32]。在人类生殖器及肠道中的微生物不会在其宿主部位以外的区域生长,因此可能会透过人类亲子之间的接触来传播[32],例如母亲的生殖器菌群传播给新生儿,很可能肠道微生物群落也会分布在婴儿的身上,例如皮肤、口腔和鼻咽等[33]

其他菌群

一般女性的阴道菌群是以乳杆菌为主,不过可能会随种族而有些差异。有些女性的阴道菌群中,有一部份是非致病英语Nonpathogenic organisms微生物[22][34],不少研究指出,在健康无症状的女性(特别是黑人及西班牙裔女性)中,有不少人(占7~33%)[35]的阴道菌群中乳杆菌的含量不多[31][36],而其菌群主要是由其他会分泌乳酸的细菌组成,例如阿托波菌(Atopobium)、纤毛菌属(Leptotrichia)、明串珠菌(Leuconostoc)、巨球形菌属(Megasphaera)、片球菌属(Pediococcus)、链球菌(Streptococcus)及魏斯氏菌(Weissella[30][31][35],所有的女性阴道菌群中都有会分泌乳酸的细菌[31][35]。不是所有的菌群都有相同的韧性,因此若阴道菌群韧性较低,其菌群结构可能会因为一些外在扰动(例如月经、性交、阴道冲洗或是避孕措施)而变化。这些阴道菌群结构及组成的差异也可能是造成一些女性较容易罹患细菌性阴道炎及其他阴道感染的原因[35][37][38]。阴道菌群可能会被外在因素影响,而其他菌种也会分泌乳酸[39],阴道的pH值以及产生酸的环境会形成正常的阴道菌群,在怀孕时,其pH值会进一步降低[40]

其他阴道中的细菌

其他阴道中常见的微生物,革兰氏阳性的球菌有阴道阿托波氏菌(Atopobium vaginae)、消化链球菌(Peptostreptococcus)、葡萄球菌属、链球菌属、和拟杆菌属、梭状芽孢杆菌属、阴道加德纳菌属、Mobiluncus及普氏菌属,也有革兰氏阴性肠道生物,例如大肠杆菌[22][23]。阴道中也常会发现支原体和解脲支原体。其中一些专性和兼性厌氧细菌和细菌性阴道炎有关[36]

争议

使用卫生棉条对阴道菌群的影响目前仍有争议,不过适当的使用卫生棉条不会大幅改变阴道菌群的平衡[需要可靠医学来源]。怀孕会改变阴道菌群,也会减少菌种的多样性[41]

疾病预防

健康的阴道菌群可以维持酸性环境(< 4.5),预防细菌性阴道病、念珠菌症等疾病,这种酸性环境不利于常见的致病原,像是阴道加德诺菌。在健康阴道菌群中,乳杆菌也占据了生态位,不然会被其他的致病原所占据[需要可靠医学来源]

细菌性阴道病和阴道中出现阴道加德诺菌英语Gardnerella vaginalis消化链球菌英语Peptostreptococcus anaerobius有关[42],也和构成健康阴道微生物群的乳杆菌种类减少有关[41][43][44][45]

研究

目前研究发现阴道存在乳酸杆菌为主的菌群,和性传染疾病发生率较低有关[46][47]

相关条目

参考资料

  1. ^ David, M. Albert und Gustav Döderlein – ein kritischer Blick auf zwei besondere Lebensläufe deutscher Ordinarien. Zentralblatt für Gynäkologie. 2006, 128 (2): 56–59. ISSN 0044-4197. doi:10.1055/s-2006-921412. 
  2. ^ 2.0 2.1 Vasquez, A.; Jakobsson, T.; Ahrne, S.; Forsum, U.; Molin, G. Vaginal Lactobacillus Flora of Healthy Swedish Women. Journal of Clinical Microbiology. 2002, 40 (8): 2746–2749. PMC 120688 . PMID 12149323. doi:10.1128/JCM.40.8.2746-2749.2002. 
  3. ^ Witkin, S. S.; Linhares, I. M.; Giraldo, P. Bacterial flora of the female genital tract: Function and immune regulation. Best Practice & Research Clinical Obstetrics & Gynaecology. 2007, 21 (3): 347–354. PMID 17215167. doi:10.1016/j.bpobgyn.2006.12.004. 
  4. ^ Graver M., Wade J. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth. Ann. Clin. Microbiol. Antimicrob. 2011, 10: 8. doi:10.1186/1476-0711-10-8. 
  5. ^ Matu M. N., Orinda G. O., Njagi E. N. M., Cohen C. R., Bukusi E. A. In vitro inhibitory activity of human vaginal lactobacilli against pathogenic bacteria associated with bacterial vaginosis in Kenyan women. Anaerobe. 2010, 16: 210–215. doi:10.1016/j.anaerobe.2009.11.002. 
  6. ^ 6.0 6.1 Skarin A., Sylwan J. Vaginal Lactobacilli inhibiting growth of Gardnerella vaginalis, Mobiluncus and other bacterial species cultured from vaginal content of women with bacterial vaginosis. APMIS. 1986, 94: 399–403. doi:10.1111/j.1699-0463.1986.tb03074.x. 
  7. ^ Strus, M., M. Malinowska, and P. B. Heczko. 2002. In vitro antagonistic effect of Lactobacillus on organisms associated with bacterial vaginosis. J. Reprod. Med. 47:41–46.
  8. ^ Boris S., Barbes C. Role played by lactobacilli in controlling the population of vaginal pathogens. Microb. Infect. 2000, 2: 543–546. doi:10.1016/s1286-4579(00)00313-0. 
  9. ^ 9.0 9.1 9.2 Martin R., Suarez J. E. Biosynthesis and degradation of H2O2 by vaginal lactobacilli. Appl. Environ. Microbiol. 2010, 76: 400–405. 
  10. ^ 10.0 10.1 10.2 10.3 10.4 10.5 O'Hanlon D., Moench T., Cone R. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect. Dis. 2011, 11: 200. doi:10.1186/1471-2334-11-200. 
  11. ^ 11.0 11.1 11.2 Aroutcheva A.; Gariti D.; Simon M.; Shott S.; Faro J.; Simoes J. A.; Gurguis A.; Faro S. Defense factors of vaginal lactobacilli. Am. J. Obstet. Gynecol. 2001, 185: 375–379. 
  12. ^ Linhares I. M., Summers P. R., Larsen B., Giraldo P. C., Witkin S. S. Contemporary perspectives on vaginal pH and lactobacilli. Am. J. Obstet. Gynecol. 2011, 204: 120.e1–120.e5. doi:10.1016/j.ajog.2010.07.010. 
  13. ^ Redondo-Lopez V.; Cook R. L.; Sobel J. D. Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev. Infect. Dis. 1990, 12: 856–872. doi:10.1093/clinids/12.5.856. 
  14. ^ Dahiya R. S.; Speck M. L. Hydrogen peroxide formation by lactobacilli and its effect on Staphylococcus aureus. J. Dairy Sci. 1968, 51: 1568–1572. doi:10.3168/jds.s0022-0302(68)87232-7. 
  15. ^ Thompson R.; Johnson A. The inhibitory action of saliva on the diphtheria Bacillus: Hydrogen peroxide, the inhibitory agent produced by salivary streptococci. J. Infect. Dis. 1951, 88: 81–85. doi:10.1093/infdis/88.1.81. 
  16. ^ Wheater D. M.; Hirsch A.; Mattick A. T. R. Possible identity of lactobacillin with hydrogen peroxide produced by lactobacilli. Nature. 1952, 170: 623–624. doi:10.1038/170623a0. 
  17. ^ 17.0 17.1 17.2 Eschenbach D. A.; Davick P. R.; Williams B. L.; Klebanoff S. J.; Young-Smith K.; Critchlow C. M.; Holmes K. K. Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis. J. Clin. Microbiol. 1989, 27: 251–256. 
  18. ^ Hillier S. L.; Krohn M. A.; Klebanoff S. J.; Eschenbach D. A. The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women. Obstet. Gynecol. 1992, 79: 369–373. doi:10.1097/00006250-199203000-00008. 
  19. ^ Klebanoff SJ. Peroxidase-mediated antimicrobial activity of rat uterine fluid. Gynecol Invest. 1970, 1: 21–30. doi:10.1159/000301903. 
  20. ^ Baeten J. M.; Hassan W. M.; Chohan V.; Richardson B. A.; Mandaliya K.; Ndinya-Achola J. O.; Jaoko W.; McClelland R. S. Prospective study of correlates of vaginal Lactobacillus colonisation among high-risk HIV-1 seronegative women. Sex. Transm. Infect. 2009, 85: 348–353. PMC 2837477 . doi:10.1136/sti.2008.035451. 
  21. ^ Wilks M., Wiggins R., Whiley A., Hennessy E., Warwick S., Porter H., Corfield A., Millar M. Identification and H2O2 production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J. Clin. Microbiol. 2004, 42: 713–717. PMC 344438 . doi:10.1128/jcm.42.2.713-717.2004. 
  22. ^ 22.0 22.1 22.2 22.3 Verhelst R., Verstraelen H., Claeys G., Verschraegen G., Simaey L. Van, De Ganck C., De Backer E., Temmerman M., Vaneechoutte M. Comparison between Gram stain and culture for the characterization of vaginal microflora: Definition of a distinct grade that resembles grade I microflora and revised categorization of grade I microflora. BMC Microbiol. 2005, 5: 61. 
  23. ^ 23.0 23.1 23.2 De Backer E., Verhelst R., Verstraelen H., Alqumber M. A., Burton J. P., Tagg J. R., Temmerman M., Vaneechoutte M. Quantitative determination by real-time PCR of four vaginal Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse relationship between L. gasseri and L. iners. BMC Microbiol. 2007, 7: 115. doi:10.1186/1471-2180-7-115. 
  24. ^ 24.0 24.1 Antonio M. A.; Hawes S. E.; Hillier S. L. The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J. Infect. Dis. 1999, 180: 1950–1956. PMID 10558952. doi:10.1086/315109. 
  25. ^ Antonio M. A. D.; Rabe L. K.; Hillier S. L. Colonization of the rectum by Lactobacillus species and decreased risk of bacterial vaginosis. J. Infect. Dis. 2005, 192: 394–398. doi:10.1086/430926. 
  26. ^ Hawes S. E.; Hillier S. L.; Benedetti J.; Stevens C. E.; Koutsky L. A.; Wolner-Hanssen P. L.; Holmes K. K. Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J. Infect. Dis. 1996, 174: 1058–1063. doi:10.1093/infdis/174.5.1058. 
  27. ^ 27.0 27.1 27.2 O'Hanlon D. E., Lanier B. R., Moench T. R., Cone R. A. Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli. BMC Infect. Dis. 2010, 10: 120. doi:10.1186/1471-2334-10-120. 
  28. ^ Klebanoff S. J.; Hillier S. L.; Eschenbach D. A.; Waltersdorph A. M. Control of the microbial flora of the vagina by H202-generating lactobacilli. J. Infect. Dis. 1991, 164: 94–100. doi:10.1093/infdis/164.1.94. 
  29. ^ Vallor A. C.; Antonio M. A.; Hawes S. E.; Hillier S. L. Factors associated with acquisition of, or persistent colonization by, vaginal lactobacilli: Role of hydrogen peroxide production. J. Infect. Dis. 2001, 184: 1431–1436. doi:10.1086/324445. 
  30. ^ 30.0 30.1 Ravel, Jacques; Gajer, Pawel; Abdo, Zaid; Schneider, G. Maria; Koenig, Sara S. K.; McCulle, Stacey L.; Karlebach, Shara; Gorle, Reshma; Russell, Jennifer; Tacket, Carol O.; Brotman, Rebecca M.; Davis, Catherine C.; Ault, Kevin; Peralta, Ligia; Forney, Larry J. Vaginal microbiome of reproductive-age women. Proceedings of the National Academy of Sciences. 15 March 2011, 108 (Supplement 1): 4680–4687 [27 May 2016]. ISSN 0027-8424. PMC 3063603 . PMID 20534435. doi:10.1073/pnas.1002611107. (原始内容存档于2019-09-06) (英语).  引用错误:带有name属性“pnas.org”的<ref>标签用不同内容定义了多次
  31. ^ 31.0 31.1 31.2 31.3 Zhou X.; Bent S. J.; Schneider M. G.; Davis C. C.; Islam M. R.; Forney L. J. Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods. Microbiology. 2004, 150: 2565–2573. doi:10.1099/mic.0.26905-0. 
  32. ^ 32.0 32.1 Danielsson D.; Teigen P. K.; Moi H. The genital econiche: Focus on microbiota and bacterial vaginosis. Ann. N. Y. Acad. Sci. 2011, 1230: 48–58. PMID 21824165. doi:10.1111/j.1749-6632.2011.06041.x. 
  33. ^ Dominguez-Bello M. G.; Costello E. K.; Contreras M.; Magris M.; Hidalgo G.; Fierer N.; Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA. 2010, 107: 11971–11975. PMC 2900693 . PMID 20566857. doi:10.1073/pnas.1002601107. 
  34. ^ Lopes, Santos Santiago G., Cools P., Verstraelen H., Trog M., Missine G., Aila N. El, Verhelst R., Tency I., Claeys G., Temmerman M., Vaneechoutte M. Longitudinal study of the dynamics of vaginal microflora during two consecutive menstrual cycles. PLOS ONE. 2011, 6: e28180. PMC 3227645 . PMID 22140538. doi:10.1371/journal.pone.0028180. 
  35. ^ 35.0 35.1 35.2 35.3 Zhou X.; Brown C. J.; Abdo Z.; Davis C. C.; Hansmann M. A.; Joyce P.; Foster J. A.; Forney L. J. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J. 2007, 1: 121–133. doi:10.1038/ismej.2007.12. 
  36. ^ 36.0 36.1 Hummelen R.; Fernandes A. D.; Macklaim J. M.; Dickson R. J.; Changalucha J.; Gloor G. B.; Reid G. Deep sequencing of the vaginal microbiota of women with HIV. PLOS ONE. 2010, 5: e12078. doi:10.1371/journal.pone.0012078. 
  37. ^ Martin J. A.; Hamilton B. E.; Sutton P. D.; Ventura S. J.; Mathews T. J.; Kirmeyer S.; Osterman M. J. Births: Final data for 2007. National vital statistics reports. 2010, 58: 1–85. 
  38. ^ Ness R. B.; Hillier S.; Richter H. E.; Soper D. E.; Stamm C.; Bass D. C.; Sweet R. L.; Rice P. Can known risk factors explain racial differences in the occurrence of bacterial vaginosis?. J. Natl. Med. Assoc. 2003, 95: 201–212. 
  39. ^ Mirmonsef P.; Gilbert D.; Veazey R. S.; Wang J.; Kendrick S. R.; Spear G. T. A comparison of lower genital tract glycogen and lactic acid levels in women and macaques: Implications for HIV and SIV susceptibility. AIDS Res. Hum. Retroviruses. 2012, 28: 76–81. PMC 3251838 . doi:10.1089/aid.2011.0071. 
  40. ^ Hillier S. L.; Nugent R. P.; Eschenbach D. A.; Krohn M. A.; Gibbs R. S.; Martin D. H.; Cotch M. F.; Edelman R.; Pastorek J. G.; Rao A. V.; McNellis D.; Regan J. A.; Carey J. C.; Klebanoff M. A. Association between bacterial vaginosis and preterm delivery of a lowbirth-weight infant. N. Engl. J. Med. 1995, 333: 1737–1742. PMID 7491137. doi:10.1056/nejm199512283332604. 
  41. ^ 41.0 41.1 Clark, Natalie; Tal, Reshef; Sharma, Harsha; Segars, James. Microbiota and Pelvic Inflammatory Disease. Seminars in Reproductive Medicine. 2014, 32 (01): 043–049. ISSN 1526-8004. PMC 4148456 . PMID 24390920. doi:10.1055/s-0033-1361822. 
  42. ^ Bacterial Vaginosis (BV): Condition Information. National Institute of Child Health and Human Development. 2013-05-21 [3 March 2015]. (原始内容存档于2015-04-02). 
  43. ^ Nardis, C.; Mastromarino, P.; Mosca, L. Vaginal microbiota and viral sexually transmitted diseases. Annali di Igiene. September 2013, 25 (5): 443–56. PMID 24048183. doi:10.7416/ai.2013.1946. 
  44. ^ What are the symptoms of bacterial vaginosis?. National Institute of Child Health and Human Development. 2013-05-21 [22 May 2016]. (原始内容存档于2015-04-02). 
  45. ^ Ravel, J. Colloquium Paper: Vaginal microbiome of reproductive-age women. Proceedings of the National Academy of Sciences. 2010, 108 (Supplement_1): 4680–4687. PMC 3063603 . PMID 20534435. doi:10.1073/pnas.1002611107. 
  46. ^ Nunn, Kenetta L.; Wang, Ying-Ying; Harit, Dimple; Humphrys, Michael S.; Ma, Bing; Cone, Richard; Ravel, Jacques; Lai, Samuel K. Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. mBio. 2015-10-06, 6 (5): e01084–15. PMC 4611035 . PMID 26443453. doi:10.1128/mBio.01084-15. 
  47. ^ Anderson, Deborah J.; Marathe, Jai; Pudney, Jeffrey. The Structure of the Human Vaginal Stratum Corneum and its Role in Immune Defense. American Journal of Reproductive Immunology. 2014-06-01, 71 (6): 618–623 [2018-11-26]. ISSN 1600-0897. PMC 4024347 . doi:10.1111/aji.12230. (原始内容存档于2017-12-12) (英语). 

外部链接