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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Nitric oxide activation by progesterone suppresses ATP-induced ciliary activity in oviductal ciliated cells

Bredford Kerr A D , Mariana Ríos B , Karla Droguett C and Manuel Villalón C D
+ Author Affiliations
- Author Affiliations

A Centro de Estudios Científicos, Av. Arturo Prat 514, 5110466, Valdivia, Chile.

B Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, 8331150 Santiago, Chile.

C Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, 8331150 Santiago, Chile.

D Corresponding authors. Emails: bkerr@cecs.cl; mvillalon@bio.puc.cl

Reproduction, Fertility and Development 30(12) 1666-1674 https://doi.org/10.1071/RD17450
Submitted: 26 October 2017  Accepted: 7 May 2018   Published: 25 June 2018

Abstract

Ciliary beat frequency (CBF) regulates the oviductal transport of oocytes and embryos, which are important components of the reproductive process. Local release of ATP transiently increases CBF by increasing [Ca2+]i. Ovarian hormones also regulate ciliary activity and oviductal transport. Progesterone (P4) induces nitric oxide (NO) production and high P4 concentrations induce ciliary dysfunction. However, the mechanism by which P4 affects CBF has not been elucidated. To evaluate the role of P4 in NO production and its effect on ATP-induced increases in CBF, we measured CBF, NO concentrations and [Ca2+]i in cultures of oviductal ciliated cells treated with P4 or NO signalling-related molecules. ATP induced a [Ca2+]i peak, followed by an increase in NO concentrations that were temporally correlated with the decreased phase of the transiently increased CBF. Furthermore, P4 increased the expression of nitric oxide synthases (iNOS and nNOS) and reduced the ATP-induced increase in CBF via a mechanism that involves the NO signalling pathway. These results have improved our knowledge about intracellular messengers controlling CBF and showed that NO attenuates oviduct cell functions. Furthermore, we showed that P4 regulates neurotransmitter (ATP) actions on CBF via the NO pathway, which could explain pathologies where oviductal transport is altered and fertility decreased.

Additional keywords: ciliary beat frequency, free intracellular Ca2+, oviduct.


References

Al-Azemi, M., Refaat, B., Am, S., Ola, B., Chapman, N., and Ledger, W. (2010). The expression of inducible nitric oxide synthase in the human Fallopian tube during the menstrual cycle and in ectopic pregnancy. Fertil. Steril. 94, 833–840.
The expression of inducible nitric oxide synthase in the human Fallopian tube during the menstrual cycle and in ectopic pregnancy.Crossref | GoogleScholarGoogle Scholar |

Barrera, N. P., Morales, B., and Villalón, M. (2004). Plasma and intracellular membrane inositol 1,4,5-trisphosphate receptors mediate the Ca2+ increase associated with the ATP-induced increase in ciliary beat frequency. Am. J. Physiol. Cell Physiol. 287, C1114–C1124.
Plasma and intracellular membrane inositol 1,4,5-trisphosphate receptors mediate the Ca2+ increase associated with the ATP-induced increase in ciliary beat frequency.Crossref | GoogleScholarGoogle Scholar |

Barrera, N. P., Morales, B., and Villalon, M. (2007). ATP and adenosine trigger the interaction of plasma membrane IP3 receptors with protein kinase A in oviductal ciliated cells. Biochem. Biophys. Res. Commun. 364, 815–821.
ATP and adenosine trigger the interaction of plasma membrane IP3 receptors with protein kinase A in oviductal ciliated cells.Crossref | GoogleScholarGoogle Scholar |

Burnstock, G. (2014). Purinergic signalling in the reproductive system in health and disease. Purinergic Signal. 10, 157–187.
Purinergic signalling in the reproductive system in health and disease.Crossref | GoogleScholarGoogle Scholar |

Bylander, A., Nutu, M., Wellander, R., Goksör, M., Billig, H., and Larsson, D. G. J. (2010). Rapid effects of progesterone on ciliary beat frequency in the mouse Fallopian tube. Reprod. Biol. Endocrinol. 8, 48–55.
Rapid effects of progesterone on ciliary beat frequency in the mouse Fallopian tube.Crossref | GoogleScholarGoogle Scholar |

Codocedo, J. F., Rodríguez, F. E., and Huidobro-Toro, J. P. (2009). Neurosteroids differentially modulate P2X ATP-gated channels through non-genomic interactions. J. Neurochem. 110, 734–744.
Neurosteroids differentially modulate P2X ATP-gated channels through non-genomic interactions.Crossref | GoogleScholarGoogle Scholar |

Codocedo, J. F., Godoy, J. A., Poblete, M. I., Inestrosa, N. C., and Huidobro-Toro, J. P. (2013). ATP induces NO production in hippocampal neurons by P2X7 receptor activation independent of glutamate signaling. PLoS One 8, e57626–e57632.
ATP induces NO production in hippocampal neurons by P2X7 receptor activation independent of glutamate signaling.Crossref | GoogleScholarGoogle Scholar |

Croxatto, H. B. (2002). Physiology of gamete and embryo transport through the Fallopian tube. Reprod. Biomed. Online 4, 160–169.
Physiology of gamete and embryo transport through the Fallopian tube.Crossref | GoogleScholarGoogle Scholar |

Droguett, K., Rios, M., Carreño, D. V., Navarrete, C., Fuentes, C., Villalón, M., and Barrera, N. P. (2017). An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium. J. Physiol. 595, 4755–4767.
An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.Crossref | GoogleScholarGoogle Scholar |

Ekerhovd, E., Brännström, M., Weijdegård, B., and Norström, A. (1999). Localization of nitric oxide synthase and effects of nitric oxide donors on the human Fallopian tube. Mol. Hum. Reprod. 5, 1040–1047.
Localization of nitric oxide synthase and effects of nitric oxide donors on the human Fallopian tube.Crossref | GoogleScholarGoogle Scholar |

Fuentealba, B., Nieto, M., and Croxatto, H. B. (1988). Estrogen and progesterone receptors in the oviduct during egg transport in cyclic and pregnant rats. Biol. Reprod. 39, 751–757.
Estrogen and progesterone receptors in the oviduct during egg transport in cyclic and pregnant rats.Crossref | GoogleScholarGoogle Scholar |

Fujii, T., Hoover, D. J., and Channing, C. P. (1983). Changes in inhibin activity, and progesterone, oestrogen and androstenedione concentrations, in rat follicular fluid throughout the oestrous cycle. J. Reprod. Fertil. 69, 307–314.
Changes in inhibin activity, and progesterone, oestrogen and androstenedione concentrations, in rat follicular fluid throughout the oestrous cycle.Crossref | GoogleScholarGoogle Scholar |

Gawronska, B., Bodek, G., and Ziecik, A. J. (2000). Distribution of NADPH-diaphorase and nitric oxide synthase (NOS) in different regions of porcine oviduct during the estrous cycle. J. Histochem. Cytochem. 48, 867–875.
Distribution of NADPH-diaphorase and nitric oxide synthase (NOS) in different regions of porcine oviduct during the estrous cycle.Crossref | GoogleScholarGoogle Scholar |

González, C., Espinosa, M., Sanchez, M. T., Droguett, K., Ríos, M., Fonseca, X., and Villalón, M. (2013). Epithelial cell culture from human adenoids: a functional study model for ciliated and secretory cells. BioMed Res. Int. 2013, 478713.
Epithelial cell culture from human adenoids: a functional study model for ciliated and secretory cells.Crossref | GoogleScholarGoogle Scholar |

Hermoso, M., Barrera, N., Morales, B., Pérez, S., and Villalón, M. (2001). Platelet activating factor increases ciliary activity in the hamster oviduct through epithelial production of prostaglandin E2. Pflügers Arch. 442, 336–345.
Platelet activating factor increases ciliary activity in the hamster oviduct through epithelial production of prostaglandin E2.Crossref | GoogleScholarGoogle Scholar |

Hunter, R. H. (2012). Components of oviduct physiology in eutherian mammals. Biol. Rev. Camb. Philos. Soc. 87, 244–255.
Components of oviduct physiology in eutherian mammals.Crossref | GoogleScholarGoogle Scholar |

Korngreen, A., and Priel, Z. (1996). Purinergic stimulation of rabbit ciliated airway epithelia: control by multiple calcium sources. J. Physiol. 497, 53–66.
Purinergic stimulation of rabbit ciliated airway epithelia: control by multiple calcium sources.Crossref | GoogleScholarGoogle Scholar |

Li, H. W., Liao, S. B., Yeung, W. S., Ng, E. H., O, W. S., and Ho, P. C. (2014). Ulipristal acetate resembles mifepristone in modulating human Fallopian tube function. Hum. Reprod. 29, 2156–2162.
Ulipristal acetate resembles mifepristone in modulating human Fallopian tube function.Crossref | GoogleScholarGoogle Scholar |

Libersky, E. A., and Boatman, D. E. (1995). Progesterone concentrations in serum, follicular fluid, and oviductal fluid of the golden hamster during the periovulatory period. Biol. Reprod. 53, 477–482.
Progesterone concentrations in serum, follicular fluid, and oviductal fluid of the golden hamster during the periovulatory period.Crossref | GoogleScholarGoogle Scholar |

Mahmood, T., Saridogan, E., Smutna, S., Habib, A. M., and Djahanbakhch, O. (1998). The effect of ovarian steroids on epithelial ciliary beat frequency in the human Fallopian tube. Hum. Reprod. 13, 2991–2994.
The effect of ovarian steroids on epithelial ciliary beat frequency in the human Fallopian tube.Crossref | GoogleScholarGoogle Scholar |

Morales, B., Barrera, N., Uribe, P., Mora, C., and Villalón, M. (2000). Functional cross talk after activation of P2 and P1 receptors in oviductal ciliated cells. Am. J. Physiol. Cell Physiol. 279, C658–C669.
Functional cross talk after activation of P2 and P1 receptors in oviductal ciliated cells.Crossref | GoogleScholarGoogle Scholar |

Nakahari, T., Nishimura, A., Shimamoto, C., Sakai, A., Kuwabara, H., Nakano, T., Tanaka, S., Kohda, Y., Matsumura, H., and Mori, H. (2011). The regulation of ciliary beat frequency by ovarian steroids in the guinea pig Fallopian tube: interactions between oestradiol and progesterone. Biomed. Res. 32, 321–328.
The regulation of ciliary beat frequency by ovarian steroids in the guinea pig Fallopian tube: interactions between oestradiol and progesterone.Crossref | GoogleScholarGoogle Scholar |

Ortiz, M. E., Villalón, M., and Croxatto, H. B. (1979). Ovum transport and fertility following postovulatory treatment with estradiol in rats. Biol. Reprod. 21, 1163–1167.
Ovum transport and fertility following postovulatory treatment with estradiol in rats.Crossref | GoogleScholarGoogle Scholar |

Paltieli, Y., Eibschitz, I., Ziskind, G., Ohel, G., Silbermann, M., and Weichselbaum, A. (2000). High progesterone levels and ciliary dysfunction – a possible cause of ectopic pregnancy. J. Assist. Reprod. Genet. 17, 103–106.
High progesterone levels and ciliary dysfunction – a possible cause of ectopic pregnancy.Crossref | GoogleScholarGoogle Scholar |

Pang, Y., and Thomas, P. (2017). Additive effects of low concentrations of estradiol-17β and progesterone on nitric oxide production by human vascular endothelial cells through shared signaling pathways. J. Steroid Biochem. Mol. Biol. 165, 258–267.
Additive effects of low concentrations of estradiol-17β and progesterone on nitric oxide production by human vascular endothelial cells through shared signaling pathways.Crossref | GoogleScholarGoogle Scholar |

Pang, Y., Dong, J., and Thomas, P. (2015). Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α. Am. J. Physiol. Endocrinol. Metab. 308, E899–E911.
Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α.Crossref | GoogleScholarGoogle Scholar |

Perez Martinez, S., Viggiano, M., Franchi, A. M., Herrero, M. B., Ortiz, M. E., Gimeno, M. F., and Villalón, M. (2000). Effect of nitric oxide synthase inhibitors on ovum transport and oviductal smooth muscle activity in the rat oviduct. J. Reprod. Fertil. 118, 111–117.

Ríos, M., Hermoso, M., Sánchez, T. M., Croxatto, H. B., and Villalón, M. J. (2007). Effect of oestradiol and progesterone on the instant and directional velocity of microsphere movements in the rat oviduct: gap junctions mediate the kinetic effect of oestradiol. Reprod. Fertil. Dev. 19, 634–640.
Effect of oestradiol and progesterone on the instant and directional velocity of microsphere movements in the rat oviduct: gap junctions mediate the kinetic effect of oestradiol.Crossref | GoogleScholarGoogle Scholar |

Sakai, A., Kondo, M., Tamaoki, J., and Konno, K. (1995). Nitric oxide modulation of Ca2+ responses in cow tracheal epithelium. Eur. J. Pharmacol. 291, 375–379.
Nitric oxide modulation of Ca2+ responses in cow tracheal epithelium.Crossref | GoogleScholarGoogle Scholar |

Saridogan, E., Djahanbakhch, O., Puddefoot, J. R., Demetroulis, C., Collingwood, K., Mehta, J. G., and Vinson, G. P. (1996). Angiotensin II receptors and angiotensin II stimulation of ciliary activity in human Fallopian tube. J. Clin. Endocrinol. Metab. 81, 2719–2725.

Shao, R., Zhang, S. X., Weijdegård, B., Zou, S., Egecioglu, E., Norström, A., Brännström, M., and Billig, H. (2010). Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights. Mol. Hum. Reprod. 16, 907–915.
Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights.Crossref | GoogleScholarGoogle Scholar |

Shen, J., Harada, N., and Yamashita, T. (2003). Nitric oxide inhibits adenosine 5′-triphosphate-induced Ca2+ response in inner hair cells of the guinea pig cochlea. Neurosci. Lett. 337, 135–138.
Nitric oxide inhibits adenosine 5′-triphosphate-induced Ca2+ response in inner hair cells of the guinea pig cochlea.Crossref | GoogleScholarGoogle Scholar |

Shen, J., Harada, N., Nakazawa, H., and Yamashita, T. (2005). Involvement of the nitric oxide–cyclic GMP pathway and neuronal nitric oxide synthase in ATP-induced Ca2+ signalling in cochlear inner hair cells. Eur. J. Neurosci. 21, 2912–2922.
Involvement of the nitric oxide–cyclic GMP pathway and neuronal nitric oxide synthase in ATP-induced Ca2+ signalling in cochlear inner hair cells.Crossref | GoogleScholarGoogle Scholar |

Torres-Fuentes, J. L., Rios, M., and Moreno, R. D. (2015). Involvement of a P2X7 receptor in the acrosome reaction induced by ATP in rat spermatozoa. J. Cell. Physiol. 230, 3068–3075.
Involvement of a P2X7 receptor in the acrosome reaction induced by ATP in rat spermatozoa.Crossref | GoogleScholarGoogle Scholar |

Uzlaner, N., and Priel, Z. (1999). Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity in rabbit trachea. J. Physiol. 516, 179–190.
Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity in rabbit trachea.Crossref | GoogleScholarGoogle Scholar |

Verdugo, P., Rumery, R. E., and Tam, P. Y. (1980). Hormonal control of oviductal ciliary activity: effect of prostaglandins. Fertil. Steril. 33, 193–196.
Hormonal control of oviductal ciliary activity: effect of prostaglandins.Crossref | GoogleScholarGoogle Scholar |

Villalón, M., and Verdugo, P. (1982). Hormonal regulation of ciliary function in the oviduct: the effect of beta-adrenergic agonists. Prog. Clin. Biol. Res. 80, 59–65.

Villalón, M., Hinds, T. R., and Verdugo, P. (1989). Stimulus–response coupling in mammalian ciliated cells. Demonstration of two mechanisms of control for cytosolic [Ca2+]. Biophys. J. 56, 1255–1258.
Stimulus–response coupling in mammalian ciliated cells. Demonstration of two mechanisms of control for cytosolic [Ca2+].Crossref | GoogleScholarGoogle Scholar |

Wang, Y., Shin, W. S., Kawaguchi, H., Inukai, M., Kato, M., Sakamoto, A., Uehara, Y., Miyamoto, M., Shimamoto, N., Korenaga, R., Ando, J., and Toyo-oka, T. (1996). Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture. J. Biol. Chem. 271, 5647–5655.
Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture.Crossref | GoogleScholarGoogle Scholar |

Wessel, T., Schuchter, U., and Walt, H. (2004). Ciliary motility in bovine oviducts for sensing rapid non-genomic reactions upon exposure to progesterone. Horm. Metab. Res. 36, 136–141.
Ciliary motility in bovine oviducts for sensing rapid non-genomic reactions upon exposure to progesterone.Crossref | GoogleScholarGoogle Scholar |

Wolfson, M. L., Schander, J. A., Bariani, M. V., Correa, F., and Franchi, A. M. (2015). Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism. Eur. J. Pharmacol. 769, 110–116.
Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.Crossref | GoogleScholarGoogle Scholar |

Yilmaz, O., Całka, J., Bukowski, R., Zalecki, M., Wasowicz, K., Jaroszewski, J. J., Markiewicz, W., Bulbul, A., and Ucar, M. (2012). Nitric oxide in the bovine oviduct: influence on contractile activity and nitric oxide synthase isoforms localization. Theriogenology 77, 1312–1327.
Nitric oxide in the bovine oviduct: influence on contractile activity and nitric oxide synthase isoforms localization.Crossref | GoogleScholarGoogle Scholar |

Zhan, X., Li, D., and Johns, R. A. (2003). Expression of endothelial nitric oxide synthase in ciliated epithelia of rats. J. Histochem. Cytochem. 51, 81–87.

Zhang, L., and Sanderson, M. J. (2003). The role of cGMP in the regulation of rabbit airway ciliary beat frequency. J. Physiol. 551, 765–776.
The role of cGMP in the regulation of rabbit airway ciliary beat frequency.Crossref | GoogleScholarGoogle Scholar |

Zhao, K. Q., Cowan, A. T., Lee, R. J., Goldstein, N., Droguett, K., Chen, B., Zheng, C., Villalon, M., Palmer, J. N., Kreindler, J. L., and Cohen, N. A. (2012). Molecular modulation of airway epithelial ciliary response to sneezing. FASEB J. 26, 3178–3187.
Molecular modulation of airway epithelial ciliary response to sneezing.Crossref | GoogleScholarGoogle Scholar |

Zicari, A., Centonze, C., Realacci, M., Buchetti, B., Pietropolli, A., and Ticconi, C. (2008). Estradiol 17-beta and progesterone modulate inducible nitric oxide synthase and high mobility group box 1 expression in human endometrium. Reprod. Sci. 15, 559–566.
Estradiol 17-beta and progesterone modulate inducible nitric oxide synthase and high mobility group box 1 expression in human endometrium.Crossref | GoogleScholarGoogle Scholar |