Physiology and Pathophysiology of the Epithelial Barrier of the Female Reproductive Tract

Role of Ion Channels
  • Hsiao Chang Chan
  • Hui Chen
  • Yechun Ruan
  • Tingting Sun
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


The epithelium lining the female reproductive tract forms a selectively permeable barrier that is responsible for creating an optimal luminal fluid microenvironment essential to the success of various reproductive events. The selective permeability of the epithelial barrier to various ions is provided by the gating of epithelial ion channels, which work together with an array of other ion transporters to drive fluid movement across the epithelium. Thus, the luminal fluid is fine-tuned by the selective barrier with tight regulation of the epithelial ion channels. This chapter discusses the role of epithelial ion channels in regulating the epithelial barrier function and thus the fluid volume and ionic composition of the female reproductive tract; physiological factors regulating the ion channels and the importance of the regulation in various reproductive events such as sperm transport and capacitation, embryo development and implantation. Disturbance of the fluid microenvironment due to defects or abnormal regulation of these ion channels and dysregulated epithelial barrier function in a number of pathological conditions, such as ovarian hyperstimulation syndrome, hydrosalpinx and infertility, are also discussed.


Cystic Fibrosis Transmembrane Conductance Regulator Epithelial Barrier Female Reproductive Tract Cervical Mucus Ovarian Hyperstimulation Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Caillouette JC, Sharp CF Jr, Zimmerman GJ et al. Vaginal pH as a marker for bacterial pathogens and menopausal status. Am J Obstet Gynecol 1997; 176(6):1270–1275; discussion 1275-1277.PubMedGoogle Scholar
  2. 2.
    Masters WH. The sexual response cycle of the human female: vaginal lubrication. Ann N Y Acad Sci 1959; 83:301–317.PubMedGoogle Scholar
  3. 3.
    Owen DH, Katz DF. A vaginal fluid simulant. Contraception 1999; 59(2):91–95.PubMedGoogle Scholar
  4. 4.
    Peeters F, Snauwaert R, Segers J et al. Observations on candidal vaginitis. Vaginal pH, microbiology, and cytology. Am J Obstet Gynecol 1972; 112(1):80–86.PubMedGoogle Scholar
  5. 5.
    Zuck TT, Duncan DRL. The time of ovulation in the human female. Am J Obstet Gynecol 1939; 38:310–313.Google Scholar
  6. 6.
    Valore EV, Park CH, Igreti SL et al. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol 2002; 187(3):561–568.PubMedGoogle Scholar
  7. 7.
    Wagner G, Levin RJ. Electrolytes in vaginal fluid during the menstrual cycle of coitally active and inactive women. J Reprod Fertil 1980; 60(1):17–27.PubMedGoogle Scholar
  8. 8.
    Eggert-Kruse W, Botz I, Pohl S et al. Antimicrobial activity of human cervical mucus. Hum Reprod 2000; 15(4):778–784.PubMedGoogle Scholar
  9. 9.
    World Health Organization, WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4 ed. 2003, Cambridge: Cambridge University Press.Google Scholar
  10. 10.
    Lamar JK, Shettles LB, Delfs E. Cyclic penetrability of human cervical mucus to spermatozoa in vitro. AM J Physiol 1940; 129:234–241.Google Scholar
  11. 11.
    Macdonald RR, Lumley IB. Endocervical pH measured in vivo through the normal menstrual cycle. Obstet Gynecol 1970; 35(2):202–206.PubMedGoogle Scholar
  12. 12.
    Moghissi KS. Cyclic changes of cervical mucus in normal and progestin-treated women. Fertil Steril 1966; 17(5):663–675.PubMedGoogle Scholar
  13. 13.
    Breckenridge MA, Pederson DP, Pommerenke WT. A pH study of human cervical secretions. Fertil Steril 1950; 1(5):427–434.PubMedGoogle Scholar
  14. 14.
    Eggert-Kruse W, Kohler A, Rohr G et al. The pH as an important determinant of sperm-mucus interaction. Fertil Steril 1993; 59(3):617–628.PubMedGoogle Scholar
  15. 15.
    Jenkins J, Anthony F, Purdie B et al. Acidic endocervical mucus: a potentially reversible cause of subfertility. Contemp Rev Obstet Gynaecol 1989; 1:273–278.Google Scholar
  16. 16.
    Zavos PM, Cohen MR. The pH of cervical mucus and the post-coital test. Fertil Steril 1980; 34(3):234–238.PubMedGoogle Scholar
  17. 17.
    Ansari AH, Gould KG, Ansari VM. Sodium bicarbonate douching for improvement of the post-coital test. Fertil Steril 1980; 33(6):608–612.PubMedGoogle Scholar
  18. 18.
    Everhardt E, Dony JM, Jansen H et al. Improvement of cervical mucus viscoelasticity and sperm penetration with sodium bicarbonate douching. Hum Reprod 1990; 5(2):133–137.PubMedGoogle Scholar
  19. 19.
    Leese HJ. The formation and function of oviduct fluid. J Reprod Fertil 1988; 82(2):843–856.PubMedGoogle Scholar
  20. 20.
    Maas DH, Storey BT, Mastroianni L Jr. Hydrogen ion and carbon dioxide content of the oviductal fluid of the rhesus monkey (Macaca mulatta). Fertility Sterility 1977; 28(9):981–985.PubMedGoogle Scholar
  21. 21.
    Hadek. Alteration of pH in the sheep’s oviduct. Nature 1953; 171:976.PubMedGoogle Scholar
  22. 22.
    Engle CC, Dunn JS, Hood RO et al. Amino acids in sow and rabbit oviduct fluids. J Anim Sci 1968; 27:1786.Google Scholar
  23. 23.
    Nichol R, Hunter RH, Cooke GM. Oviduct fluid pH in intact and unilaterally ovariectomized pigs. Can J Physiol Pharmacol 1997; 75(9):1069–1074.PubMedGoogle Scholar
  24. 24.
    Murdoch RN, White IG. The influence of the female genital tract on the metabolism of rabbit spermatozoa. I. Direct effect of tubal and uterine fluids, bicarbonate, and other factors. Australian Journal of Biological Sciences 1968; 21(5):961–972.PubMedGoogle Scholar
  25. 25.
    Odor DL, Blandau RJ. Observations on the solitary cilium of rabbit oviductal epithelium: its motility and ultrastructure. Am J Anat 1985; 174(4):437–453.PubMedGoogle Scholar
  26. 26.
    Vishwakarma P. The pH and bicarbonate-ion content of the oviduct and uterine fluids. Fertility & Sterility 1962; 13:481–485.Google Scholar
  27. 27.
    Casslen B, Nilsson B. Human uterine fluid, examined in undiluted samples for osmolarity and the concentrations of inorganic ions, albumin, glucose, and urea. Am J Obstet Gynecol 1984; 150(7):877–881.PubMedGoogle Scholar
  28. 28.
    Clemetson CA, Kim JK, De Jesus TP et al. Human uterine fluid potassium and the menstrual cycle. J Obstet Gynaecol Br Commonw 1973; 80(6):553–561.PubMedGoogle Scholar
  29. 29.
    Clemetson CA, Mallikarjuneswara VR, Moshfeghi MM et al. The effects of oestrogen and progesterone on the sodium and potassium concentrations of rat uterine fluid. J Endocrinol 1970; 47(3):309–319.PubMedGoogle Scholar
  30. 30.
    Iritani A, Sato E, Nishikawa Y. Secretion rates and chemical composition of oviduct and uterine fluids in sows. J Anim Sci 1974; 39(3):582–588.PubMedGoogle Scholar
  31. 31.
    Nilsson BO, Ljung L. X-ray micro analyses of cations (Na, K, Ca) and anions (S, P, Cl) in uterine secretions during blastocyst implantation in the rat. J Exp Zool 1985; 234(3):415–421.PubMedGoogle Scholar
  32. 32.
    Nordenvall M, Ulmsten U, Ungerstedt U. Influence of progesterone on the sodium and potassium concentrations of rat uterine fluid investigated by microdialysis. Gynecol Obstet Invest 1989; 28(2):73–77.PubMedGoogle Scholar
  33. 33.
    Dickens CJ, Maguiness SD, Comer MT et al. Human tubal fluid: formation and composition during vascular perfusion of the fallopian tube. Hum Reprod 1995; 10(3):505–508.PubMedGoogle Scholar
  34. 34.
    Hunter RH. Fallopian tube fluid: the physiological medium for fertilization and early embryo development. ed. The Fallopian Tubes: Their Role in Fertility and Infertility Berlin: Springer-Verlag, 1988; 30–52.Google Scholar
  35. 35.
    Miller JG, Schultz GA. Amino acid content of pre-implantation rabbit embryos and fluids of the reproductive tract. Biol Reprod 1987; 36(1):125–129.PubMedGoogle Scholar
  36. 36.
    Tay JI, Rutherford AJ, Killick SR et al. Human tubal fluid: production, nutrient composition and response to adrenergic agents. Hum Reprod 1997; 12(11):2451–2456.PubMedGoogle Scholar
  37. 37.
    Downing SJ, Maguiness SD, Watson A et al. Electrophysiological basis of human fallopian tubal fluid formation. J Reprod Fertil 1997; 111(1):29–34.PubMedGoogle Scholar
  38. 38.
    Leese HJ, Tay JI, Reischl J et al. Formation of Fallopian tubal fluid: role of a neglected epithelium. Reproduction 2001; 121(3):339–346.PubMedGoogle Scholar
  39. 39.
    Long JA, Evans HM. The oestrous cycle in the rat and its associated phenomena. Proc Natl Acad Sci U S A 1922; 8(3):8–39.Google Scholar
  40. 40.
    He Q, Tsang LL, Ajonuma LC et al. Abnormally up-regulated cystic fibrosis transmembrane conductance regulator expression and uterine fluid accumulation contribute to Chlamydia trachomatis-induced female infertility. Fertil Steril 2010; 93(8):2608–2614.PubMedGoogle Scholar
  41. 41.
    Casslen B. Uterine fluid volume. Cyclic variations and possible extrauterine contributions. J Reprod Med 1986; 31(6):506–510.PubMedGoogle Scholar
  42. 42.
    Kopito LE, Kosasky HJ, Sturgis SH et al. Water and electrolytes in human cervical mucus. Fertil Steril 1973; 24(7): 499–506.PubMedGoogle Scholar
  43. 43.
    Chan HC, Liu CQ, Fong SK et al. Electrogenic ion transport in the mouse endometrium: functional aspects of the cultured epithelium. Biochim Biophys Acta 1997; 1356(2):140–148.PubMedGoogle Scholar
  44. 44.
    Matthews CJ, McEwan GT, Redfern CP et al. Absorptive apical amiloride-sensitive Na+ conductance in human endometrial epithelium. J Physiol 1998; 513(Pt 2):443–452.PubMedGoogle Scholar
  45. 45.
    Deachapunya C, Palmer-Densmore M, O’Grady SM. Insulin stimulates transepithelial sodium transport by activation of a protein phosphatase that increases Na-K ATPase activity in endometrial epithelial cells. J Gen Physiol 1999; 114(4):561–574.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Chan HC, Fong SK, So SC et al. Stimulation of anion secretion by beta-adrenoceptors in the mouse endometrial epithelium. J Physiol 1997; 501(Pt 3):517–525.PubMedGoogle Scholar
  47. 47.
    Chan HC, Liu CQ, Fong SK et al. Regulation of Cl-secretion by extracellular ATP in cultured mouse endometrial epithelium. J Membr Biol 1997; 156(1):45–52.PubMedGoogle Scholar
  48. 48.
    Chan LN, Tsang LL, Rowlands DK et al. Distribution and regulation of ENaC subunit and CFTR mRNA expression in murine female reproductive tract. J Membr Biol 2002; 185(2):165–176.PubMedGoogle Scholar
  49. 49.
    Fong SK, Chan HC. Regulation of anion secretion by prostaglandin E2 in the mouse endometrial epithelium. Biol Reprod 1998; 58(4):1020–1025.PubMedGoogle Scholar
  50. 50.
    Fong SK, Liu CQ, Chan HC. Cellular mechanisms of adrenaline-stimulated anion secretion by the mouse endometrial epithelium. Biol Reprod 1998; 59(6):1342–1348.PubMedGoogle Scholar
  51. 51.
    Sheppard DN, Welsh MJ. Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. J Gen Physiol 1992; 100(4):573–591.PubMedGoogle Scholar
  52. 52.
    Reisin IL, Prat AG, Abraham EH et al. The cystic fibrosis transmembrane conductance regulator is a dual ATP and chloride channel. J Biol Chem 1994; 269(32):20584–20591.PubMedGoogle Scholar
  53. 53.
    Haws C, Finkbeiner WE, Widdicombe JH et al. CFTR in Calu-3 human airway cells: channel properties and role in cAMP-activated Cl-conductance. Am J Physiol 1994; 266(5 Pt 1):L502–L512.PubMedGoogle Scholar
  54. 54.
    Deachapunya C, O’Grady SM. Regulation of chloride secretion across porcine endometrial epithelial cells by prostaglandin E2. J Physiol 1998; 508(Pt 1):31–47.PubMedGoogle Scholar
  55. 55.
    Chan LN, Chung YW, Leung PS et al. Activation of an adenosine 3′, 5′-cyclic monophosphate-dependent Cl-conductance in response to neurohormonal stimuli in mouse endometrial epithelial cells: the role of cystic fibrosis transmembrane conductance regulator. Biol Reprod 1999; 60(2):374–380.PubMedGoogle Scholar
  56. 56.
    Wang XF, Zhou CX, Shi QX et al. Involvement of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Nat Cell Biol 2003; 5(10):902–906.PubMedGoogle Scholar
  57. 57.
    Wang XF, Yu MK, Leung KM et al. Involvement of Na+-HCO3-cotransporter in mediating cyclic adenosine 3′, 5′-monophosphate-dependent HCO3-secretion by mouse endometrial epithelium. Biol Reprod 2002; 66(6):1846–1852.PubMedGoogle Scholar
  58. 58.
    Wang XF, Yu MK, Lam SY et al. Expression, immunolocalization, and functional activity of Na+/H+ exchanger isoforms in mouse endometrial epithelium. Biol Reprod 2003; 68(1):302–308.PubMedGoogle Scholar
  59. 59.
    Brunton WJ, Brinster RL. Active chloride transport in the isolated rabbit oviduct. AM J Physiol 1971; 221(2):658–661.PubMedGoogle Scholar
  60. 60.
    Gott AL, Gray SM, James AF et al. The mechanism and control of rabbit oviduct fluid formation. Biol Reprod 1988; 39(4):758–763.PubMedGoogle Scholar
  61. 61.
    Dickens CJ, Southgate J, Leese HJ. Use of primary cultures of rabbit oviduct epithelial cells to study the ionic basis of tubal fluid formation. J Reprod Fertil 1993; 98(2):603–610.PubMedGoogle Scholar
  62. 62.
    Keating N, Quinlan LR. Effect of basolateral adenosine triphosphate on chloride secretion by bovine oviductal epithelium. Biol Reprod 2008; 78(6):1119–1126.PubMedGoogle Scholar
  63. 63.
    Dickens CJ, Leese HJ. The regulation of rabbit oviduct fluid formation. J Reprod Fertil 1994; 100 (2):577–581.Google Scholar
  64. 64.
    Leung AY, Wong PY, Gabriel SE et al. cAMP-but not Ca(2+)-regulated Cl-conductance in the oviduct is defective in mouse model of cystic fibrosis. AM J Physiol 1995; 268(3 Pt 1):C708–C712.PubMedGoogle Scholar
  65. 65.
    Chen MH, Chen H, Zhou Z et al. Involvement of CFTR in oviductal HCO3-secretion and its effect on soluble adenylate cyclase-dependent early embryo development. Hum Reprod 2010; 25(7):1744–1754.PubMedGoogle Scholar
  66. 66.
    Agre P, Preston GM, Smith BL et al. Aquaporin CHIP: the archetypal molecular water channel. AM J Physiol 1993; 265(4 Pt 2):F463–F476.PubMedGoogle Scholar
  67. 67.
    He RH, Sheng JZ, Luo Q et al. Aquaporin-2 expression in human endometrium correlates with serum ovarian steroid hormones. Life Sci 2006; 79(5):423–429.PubMedGoogle Scholar
  68. 68.
    Hildenbrand A, Lalitkumar L, Nielsen S et al. Expression of aquaporin 2 in human endometrium. Fertil Steril 2006; 86(5):1452–1458.PubMedGoogle Scholar
  69. 69.
    Lindsay LA, Murphy CR. Redistribution of aquaporins in uterine epithelial cells at the time of implantation in the rat. Acta Histochem 2004; 106(4):299–307.PubMedGoogle Scholar
  70. 70.
    Lindsay LA, Murphy CR. Redistribution of aquaporins 1 and 5 in the rat uterus is dependent on progesterone: a study with light and electron microscopy. Reproduction 2006; 131(2):369–378.PubMedGoogle Scholar
  71. 71.
    Skowronski MT, Kwon TH, Nielsen S. Immunolocalization of aquaporin 1, 5, and 9 in the female pig reproductive system. J Histochem Cytochem 2009; 57(1):61–67.PubMedGoogle Scholar
  72. 72.
    Branes MC, Morales B, Rios M et al. Regulation of the immunoexpression of aquaporin 9 by ovarian hormones in the rat oviductal epithelium. Am J Physiol Cell Physiol 2005; 288(5):C1048–1057.PubMedGoogle Scholar
  73. 73.
    Skowronski MT, Skowronska A, Nielsen S. Fluctuation of aquaporin 1, 5, and 9 expression in the pig oviduct during the estrous cycle and early pregnancy. J Histochem Cytochem 2011; 59(4):419–427.PubMedGoogle Scholar
  74. 74.
    Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 1993; 73(7):1251–1254.PubMedGoogle Scholar
  75. 75.
    Di A, Brown ME, Deriy LV et al. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol 2006; 8(9):933–944.PubMedGoogle Scholar
  76. 76.
    Guo Y, Su M, McNutt MA et al. Expression and distribution of cystic fibrosis transmembrane conductance regulator in neurons of the human brain. J Histochem Cytochem 2009; 57(12):1113–1120.PubMedGoogle Scholar
  77. 77.
    Tousson A, Van Tine BA, Naren AP et al. Characterization of CFTR expression and chloride channel activity in human endothelia. Am J Physiol 1998; 275(6 Pt 1):C1555–C1564.PubMedGoogle Scholar
  78. 78.
    Quinton PM. Physiological basis of cystic fibrosis: a historical perspective. Physiol Rev 1999; 79(Suppl 1):S3–S22.PubMedGoogle Scholar
  79. 79.
    Zhang WK, Wang D, Duan Y et al. Mechanosensitive gating of CFTR. Nat Cell Biol 2010; 12(5):507–512.PubMedGoogle Scholar
  80. 80.
    Rubenstein RC, Lockwood SR, Lide E et al. Regulation of endogenous ENaC functional expression by CFTR and DeltaF508-CFTR in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2011; 300(1):L88–L101.PubMedGoogle Scholar
  81. 81.
    Gawenis LR, Franklin CL, Simpson JE et al. cAMP inhibition of murine intestinal Na/H exchange requires CFTR-mediated cell shrinkage of villus epithelium. Gastroenterology 2003; 125(4):1148–1163.PubMedGoogle Scholar
  82. 82.
    Park M, Ko SB, Choi JY et al. The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3 salvage transporter human Na+-HCO3 cotransport isoform 3. J Biol Chem 2002; 277(52):50503–50509.PubMedGoogle Scholar
  83. 83.
    Li C, Naren AP. CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners. Integr Biol (Camb) 2010; 2(4):161–177.Google Scholar
  84. 84.
    Kellenberger S, Schild L. Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev 2002; 82(3):735–767.PubMedGoogle Scholar
  85. 85.
    Hummler E, Rossier BC. Physiological and pathophysiological role of the epithelial sodium channel in the control of blood pressure. Kidney Blood Press Res 1996; 19(3–4):160–165.PubMedGoogle Scholar
  86. 86.
    Soundararajan R, Pearce D, Hughey RP et al. Role of epithelial sodium channels and their regulators in hypertension. J Biol Chem 2010; 285(40):30363–30369.PubMedGoogle Scholar
  87. 87.
    Hummler E, Barker P, Gatzy J et al. Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice. Nat Genet 1996; 12(3):325–328.PubMedGoogle Scholar
  88. 88.
    Schwartz GJ, Burg MB. Mineralocorticoid effects on cation transport by cortical collecting tubules in vitro. Am J Physiol 1978; 235(6):F576–F585.PubMedGoogle Scholar
  89. 89.
    Schild L, Canessa CM, Shimkets RA et al. A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system. Proc Natl Acad Sci U S A 1995; 92(12):5699–5703.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Chang SS, Grunder S, Hanukoglu A et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 1996; 12(3):248–253.PubMedGoogle Scholar
  91. 91.
    Mularoni A, Beck L, Sadir R et al. Down-regulation by progesterone of CFTR expression in endometrial epithelial cells: a study by competitive RT-PCR. Biochem Biophys Res Commun 1995; 217(3):1105–1111.PubMedGoogle Scholar
  92. 92.
    Rochwerger L, Buchwald M. Stimulation of the cystic fibrosis transmembrane regulator expression by estrogen in vivo. Endocrinology 1993; 133(2):921–930.PubMedGoogle Scholar
  93. 93.
    Rochwerger L, Dho S, Parker L et al. Estrogen-dependent expression of the cystic fibrosis transmembrane regulator gene in a novel uterine epithelial cell line. J Cell Sci 1994; 107(Pt 9):2439–2448.PubMedGoogle Scholar
  94. 94.
    Salleh N, Baines DL, Naftalin RJ et al. The hormonal control of uterine luminal fluid secretion and absorption. J Membr Biol 2005; 206(1):17–28.PubMedGoogle Scholar
  95. 95.
    Laube M, Kuppers E, Thome UH. Modulation of sodium transport in alveolar epithelial cells by estradiol and progesterone. Pediatr Res 2011; 69(3):200–205.PubMedGoogle Scholar
  96. 96.
    Gambling L, Dunford S, Wilson CA et al. Estrogen and progesterone regulate alpha, beta, and gammaENaC subunit mRNA levels in female rat kidney. Kidney Int 2004; 65(5):1774–1781.PubMedGoogle Scholar
  97. 97.
    Chang CT, Sun CY, Pong CY et al. Interaction of estrogen and progesterone in the regulation of sodium channels in collecting tubular cells. Chang Gung Med J 2007; 30(4):305–312.PubMedGoogle Scholar
  98. 98.
    Ajonuma LC, Chan PK, Ng EH et al. Involvement of cystic fibrosis transmembrane conductance regulator (CFTR ) in the pathogenesis of hydrosalpinx induced by Chlamydia trachomatis infection. J Obstet Gynaecol Res 2008; 34(6):923–930.PubMedGoogle Scholar
  99. 99.
    Yang JZ, Ajonuma LC, Tsang LL et al. Differential expression and localization of CFTR and ENaC in mouse endometrium during pre-implantation. Cell Biol Int 2004; 28(6):433–439.PubMedGoogle Scholar
  100. 100.
    Chan LN, Wang XF, Tsang LL et al. Inhibition of amiloride-sensitive Na(+) absorption by activation of CFTR in mouse endometrial epithelium. Pflugers Arch 2001; 443 Suppl 1:S132–S136.PubMedGoogle Scholar
  101. 101.
    Bishop DW. Active secretion in the rabbit oviduct. Am J Physiol 1956; 187(2):347–352.PubMedGoogle Scholar
  102. 102.
    Richardson LL, Oliphant G. Steroid concentrations in rabbit oviducal fluid during oestrus and pseudopregnancy. J Reprod Fertil 1981; 62(2):427–431.PubMedGoogle Scholar
  103. 103.
    Perkins JL. Fluid flow of the oviduct. In Johnson AD, Foley CW, ed. The Oviduct and its Functions. New York, London: Academic Press, 1974:119–132.Google Scholar
  104. 104.
    Roberts GP, Parker JM, Symonds HW. Proteins in the luminal fluid from the bovine oviduct. J Reprod Fertil 1975; 45(2):301–313.PubMedGoogle Scholar
  105. 105.
    Mastroianni L Jr, Beer F, Shah U et al. Endocrine regulation of oviduct secretions in the rabbit. Endocrinology 1961; 68:92–100.PubMedGoogle Scholar
  106. 106.
    McDonald MF, Bellve AR. Influence of oestrogen and progesterone on flow of fluid from the Fallopian tube in the ovariectomized ewe. J Reprod Fertil 1969; 20(1):51–61.PubMedGoogle Scholar
  107. 107.
    Chen M, Du J, Jiang W et al. Functional expression of cystic fibrosis transmembrane conductance regulator in rat oviduct epithelium. Acta Biochim Biophys Sin (Shanghai) 2008; 40(10):864–872.Google Scholar
  108. 108.
    Donaldson SH, Poligone EG, Stutts MJ. CFTR regulation of ENaC. Methods Mol Med 2002; 70:343–364.PubMedGoogle Scholar
  109. 109.
    Kunzelmann K. ENaC is inhibited by an increase in the intracellular Cl(−) concentration mediated through activation of Cl(−) channels. Pflugers Arch 2003; 445(4):504–512.PubMedGoogle Scholar
  110. 110.
    Wang XF, Chan HC. Adenosine triphosphate induces inhibition of Na(+) absorption in mouse endometrial epithelium: a Ca(2+)-dependent mechanism. Biol Reprod 2000; 63(6):1918–1924.PubMedGoogle Scholar
  111. 111.
    Chan LN, Wang XF, Tsang LL et al. Suppression of CFTR-mediated Cl(−) secretion by enhanced expression of epithelial Na(+) channels in mouse endometrial epithelium. Biochem Biophys Res Commun 2000; 276(1):40–44.PubMedGoogle Scholar
  112. 112.
    Wang XF, Tsang LL, So SC et al. Suppression of ATP-induced Cl(−)secretion by enhanced expression of epithelial Na(+)channels in mouse endometrial epithelium. Cell Biol Int 2001; 25(10):1017–1020.PubMedGoogle Scholar
  113. 113.
    Benos DJ, Awayda MS, Berdiev BK et al. Diversity and regulation of amiloride-sensitive Na+ channels. Kidney Int 1996; 49(6):1632–1637.PubMedGoogle Scholar
  114. 114.
    Tsang LL, Chan LN, Chan HC. Altered cyclic expression of epithelial Na+ channel subunits and cystic fibrosis transmembrane conductance regulator in mouse endometrium by a low sodium diet. Cell Biol Int 2004; 28(7):549–555.PubMedGoogle Scholar
  115. 115.
    Tsang LL, Chan LN, Wang XF et al. Enhanced epithelial Na(+) channel (ENaC) activity in mouse endometrial epithelium by upregulation of gammaENaC subunit. Jpn J Physiol 2001; 51(4):539–543.PubMedGoogle Scholar
  116. 116.
    Calhoun DA. Aldosteronism and hypertension. Clin J Am Soc Nephrol 2006; 1(5):1039–1045.PubMedGoogle Scholar
  117. 117.
    Yang JZ, Ho AL, Ajonuma LC et al. Differential effects of Matrigel and its components on functional activity of CFTR and ENaC in mouse endometrial epithelial cells. Cell Biol Int 2003; 27(7):543–548.PubMedGoogle Scholar
  118. 118.
    Althaus M, Bogdan R, Clauss WG et al. Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability. FASEB J 2007; 21(10):2389–2399.PubMedGoogle Scholar
  119. 119.
    Bengrine A, Li J, Hamm LL et al. Indirect activation of the epithelial Na+ channel by trypsin. J Biol Chem 2007; 282(37):26884–26896.PubMedGoogle Scholar
  120. 120.
    Donaldson SH, Hirsh A, Li DC et al. Regulation of the epithelial sodium channel by serine proteases in human airways. J Biol Chem 2002; 277(10):8338–8345.PubMedGoogle Scholar
  121. 121.
    He Q, Chen H, Wong CH et al. Regulatory mechanism underlying cyclic changes in mouse uterine bicarbonate secretion: role of estrogen. Reproduction 2010; 140(6):903–910.PubMedGoogle Scholar
  122. 122.
    Boatman DE, Robbins RS. Bicarbonate: carbon-dioxide regulation of sperm capacitation, hyperactivated motility, and acrosome reactions. Biol Reprod 1991; 44(5):806–813.PubMedGoogle Scholar
  123. 123.
    Shi QX, Roldan ER. Bicarbonate/CO2 is not required for zona pellucida-or progesterone-induced acrosomal exocytosis of mouse spermatozoa but is essential for capacitation. Biol Reprod 1995; 52(3):540–546.PubMedGoogle Scholar
  124. 124.
    Oppenheimer EA, Case AL, Esterly JR et al. Cervical mucus in cystic fibrosis: a possible cause of infertility. Am J Obstet Gynecol 1970; 108(4):673–674.PubMedGoogle Scholar
  125. 125.
    Kopito LE, Kosasky HJ, Shwachman H. Water and electrolytes in cervical mucus from patients with cystic fibrosis. Fertil Steril 1973; 24(7):512–516.PubMedGoogle Scholar
  126. 126.
    Quinton PM. Role of epithelial HCO3 transport in mucin secretion: lessons from cystic fibrosis. Am J Physiol Cell Physiol 2010; 299(6):C1222–C1233.PubMedGoogle Scholar
  127. 127.
    Muchekehu RW, Quinton PM. A new role for bicarbonate secretion in cervico-uterine mucus release. J Physiol 2010; 588(Pt 13):2329–2342.PubMedGoogle Scholar
  128. 128.
    Garcia MA, Yang N, Quinton PM. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest 2009; 119(9):2613–2622.PubMedCentralPubMedGoogle Scholar
  129. 129.
    Epelboin S, Hubert D, Patrat C et al. Management of assisted reproductive technologies in women with cystic fibrosis. Fertil Steril 2001; 76(6):1280–1281.PubMedGoogle Scholar
  130. 130.
    O kamura N, Tajima Y, Soejima A et al. Sodium bicarbonate in seminal plasma stimulates the motility of mammalian spermatozoa through direct activation of adenylate cyclase. J Biol Chem 1985; 260(17):9699–9705.Google Scholar
  131. 131.
    Vishwakarma P. The pH and bicarbonate-ion content of the oviduct and uterine fluids. Fertil Steril 1962; 13:481–485.PubMedGoogle Scholar
  132. 132.
    Matzuk MM, Lamb DJ. Genetic dissection of mammalian fertility pathways. Nat Cell Biol 2002; 4 Suppl:s41–s49.PubMedGoogle Scholar
  133. 133.
    Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update 2002; 8(6):559–577.PubMedGoogle Scholar
  134. 134.
    Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril 1978; 30(3):255–268.PubMedGoogle Scholar
  135. 135.
    Nastri CO, Ferriani RA, Rocha IA et al. Ovarian hyperstimulation syndrome: pathophysiology and prevention. J Assist Reprod Genet; 27(2–3):121–128.Google Scholar
  136. 136.
    Enskog A, Nilsson L, Brannstrom M. Plasma levels of free vascular endothelial growth factor(165) (VEGF(165)) are not elevated during gonadotropin stimulation in in vitro fertilization (IVF) patients developing ovarian hyperstimulation syndrome (OHSS): results of a prospective cohort study with matched controls. Eur J Obstet Gynecol Reprod Biol 2001; 96(2):196–201.PubMedGoogle Scholar
  137. 137.
    Geva E, Amit A, Lessing JB et al. Follicular fluid levels of vascular endothelial growth factor. Are they predictive markers for ovarian hyperstimulation syndrome? J Reprod Med 1999; 44(2):91–96.PubMedGoogle Scholar
  138. 138.
    Kobayashi H, Okada Y, Asahina T et al. The kallikrein-kinin system, but not vascular endothelial growth factor, plays a role in the increased vascular permeability associated with ovarian hyperstimulation syndrome. J Mol Endocrinol 1998; 20(3):363–374.PubMedGoogle Scholar
  139. 139.
    McElhinney B, Ardill J, Caldwell C et al. Variations in serum vascular endothelial growth factor binding profiles and the development of ovarian hyperstimulation syndrome. Fertil Steril 2002; 78(2):286–290.PubMedGoogle Scholar
  140. 140.
    Gomez R, Simon C, Remohi J et al. Administration of moderate and high doses of gonadotropins to female rats increases ovarian vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression that is associated to vascular hyperpermeability. Biol Reprod 2003; 68(6):2164–2171.PubMedGoogle Scholar
  141. 141.
    Wang TH, Horng SG, Chang CL et al. Human chorionic gonadotropin-induced ovarian hyperstimulation syndrome is associated with up-regulation of vascular endothelial growth factor. J Clin Endocrinol Metab 2002; 87(7):3300–3308.PubMedGoogle Scholar
  142. 142.
    Villasante A, Pacheco A, Ruiz A et al. Vascular endothelial cadherin regulates vascular permeability: Implications for ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 2007; 92(1):314–321.PubMedGoogle Scholar
  143. 143.
    Rodewald M, Herr D, Duncan WC et al. Molecular mechanisms of ovarian hyperstimulation syndrome: paracrine reduction of endothelial claudin 5 by hCG in vitro is associated with increased endothelial permeability. Hum Reprod 2009; 24(5):1191–1199.PubMedGoogle Scholar
  144. 144.
    Gabriel SE, Brigman KN, Koller BH et al. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science 1994; 266(5182):107–109.PubMedGoogle Scholar
  145. 145.
    Ajonuma LC, Tsang LL, Zhang GH et al. Estrogen-induced abnormally high cystic fibrosis transmembrane conductance regulator expression results in ovarian hyperstimulation syndrome. Mol Endocrinol 2005; 19(12):3038–3044.PubMedGoogle Scholar
  146. 146.
    Manau D, Balasch J, Arroyo V et al. Circulatory dysfunction in asymptomatic in vitro fertilization patients. Relationship with hyperestrogenemia and activity of endogenous vasodilators. J Clin Endocrinol Metab 1998; 83(5):1489–1493.PubMedGoogle Scholar
  147. 147.
    Cates W Jr, Wasserheit JN. Genital chlamydial infections: epidemiology and reproductive sequelae. Am J Obstet Gynecol 1991; 164(6 Pt 2):1771–1781.PubMedGoogle Scholar
  148. 148.
    Walters MD, Eddy CA, Gibbs RS et al. Antibodies to Chlamydia trachomatis and risk for tubal pregnancy. Am J Obstet Gynecol 1988; 159(4):942–946.PubMedGoogle Scholar
  149. 149.
    Wolner-Hanssen P, Mardh PA, Moller B et al. Endometrial infection in women with Chlamydial salpingitis. Sex Transm Dis 1982; 9(2):84–88.PubMedGoogle Scholar
  150. 150.
    Jones RB, Mammel JB, Shepard MK et al. Recovery of Chlamydia trachomatis from the endometrium of women at risk for chlamydial infection. Am J Obstet Gynecol 1986; 155(1):35–39.PubMedGoogle Scholar
  151. 151.
    Witkin SS, Sultan KM, Neal GS et al. Unsuspected Chlamydia trachomatis infection and in vitro fertilization outcome. Am J Obstet Gynecol 1994; 171(5):1208–1214.PubMedGoogle Scholar
  152. 152.
    Spandorfer SD, Neuer A, LaVerda D et al. Previously undetected Chlamydia trachomatis infection, immunity to heat shock proteins and tubal occlusion in women undergoing in-vitro fertilization. Hum Reprod 1999; 14(1):60–64.PubMedGoogle Scholar
  153. 153.
    Ajonuma LC, Ng EH, Chan LN et al. Ultrastructural characterization of whole hydrosalpinx from infertile Chinese women. Cell Biol Int 2005; 29(10):849–856.PubMedGoogle Scholar
  154. 154.
    Ajonuma LC, Ng EH, Chow PH et al. Increased cystic fibrosis transmembrane conductance regulator (CFTR ) expression in the human hydrosalpinx. Hum Reprod 2005; 20(5):1228–1234.PubMedGoogle Scholar
  155. 155.
    Ajonuma LC, He Q, Sheung Chan PK et al. Involvement of cystic fibrosis transmembrane conductance regulator in infection-induced edema. Cell Biol Int 2008; 32(7):801–806.PubMedGoogle Scholar
  156. 156.
    Mansour RT, Aboulghar MA, Serour GI et al. Fluid accumulation of the uterine cavity before embryo transfer: a possible hindrance for implantation. J In Vitro Fert Embryo Transf 1991; 8(3):157–159.PubMedGoogle Scholar
  157. 157.
    Lebech PE, Svendsen PA, Ostergaard E. The effects of small doses of megestrol acetate on the cervical mucus. Int J Fertil 1970; 15(2):65–76.PubMedGoogle Scholar
  158. 158.
    Edwards RG, Talbert L, Israelstam D et al. Diffusion chamber for exposing spermatozoa to human uterine secretions. Am J Obstet Gynecol 1968; 102(3):388–396.PubMedGoogle Scholar
  159. 159.
    Kar AB, Engineer AD, Goel R et al. Effect of an intrauterine contraceptive device on biochemical composition of uterine fluid. Am J Obstet Gynecol 1968; 101(7):966–970.PubMedGoogle Scholar
  160. 160.
    Maas DHA, Reiss G, Braun D. pH, pCO2, and lactate concentration in human uterine fluid. Arch Androl 1983; 11:188.Google Scholar
  161. 161.
    Lippes J, Enders RG, Pragay DA et al. The collection and analysis of human fallopian tubal fluid. Contraception 1972; 5(2):85–103.PubMedGoogle Scholar
  162. 162.
    Borland RM, Hazra S, Biggers JD et al. The elemental composition of the environments of the gametes and pre-implantation embryo during the initiation of pregnancy. Biol Reprod 1977; 16(2):147–157.PubMedGoogle Scholar
  163. 163.
    David A, Brackett BG, Garcia CR et al. Composition of rabbit oviduct fluid in ligated segments of the Fallopian tube. J Reprod Fertil 1969; 19(2):285–289.PubMedGoogle Scholar
  164. 164.
    Strandell A, Sjogren A, Bentin-Ley U et al. Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro. Hum Reprod 1998; 13(10):2921–2925.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2013

Authors and Affiliations

  • Hsiao Chang Chan
    • 1
  • Hui Chen
    • 1
  • Yechun Ruan
    • 1
  • Tingting Sun
    • 1
  1. 1.Epithelial Cell Biology Research Center, School of Biomedical SciencesThe Chinese University of Hong KongHong KongChina

Personalised recommendations