Sperm Transport Through the Female Reproductive Tract

Sperm Transport Through the Female Reproductive Tract

Contenido principal del artículo

Pilar Vigil
Ismael Valdés-Undurraga
Juan del Río
Manuel Cortés

Resumen

Mammalian spermatozoa are highly complex specialized cells that survive a long and fascinating journey from the site of insemination to the upper third of the oviduct, where fertilization occurs. During this journey, these cells have to go through different microenvironments, which provide appropriate conditions for the occurrence of sperm capacitation and acrosome reaction (AR) in the time and place needed. These events need to occur in an extremely synchronized sequence in order to assure that fertilization takes place. The objective of this review article is to describe and analyze the various changes that spermatozoa will experience during their journey through the female genital tract and how they are influenced by the epithelium and secretions present in the cervix, endometrium and oviduct. These microenvironments will prevent the AR from occurring ahead of time as in the case of estrogenic cervical mucus or will stimulate its occurrence as in the case of progesterone, present during ovulation in oviductal fluid. In all cases the female reproductive tract will supply the conditions needed to guarantee survival, capacitation, AR and migration of spermatozoa for subsequent fusion with the oocyte. These microenvironments contain various hormones, neurotransmitters and other metabolites for which spermatozoa have specific receptors through which these substances can modulate their fertilizing potential. The study and understanding of the physiological conditions needed for gamete membrane fusion to occur is an important aspect to be considered both in basic and applied research in reproductive biology.

Citas

Adamopoulos, D. A.; Kapolla, N.; Abrahamian, A.; Dessypris, A.; Nicopoulou, S. & Giannacodemos, G. Sex steroids in cervical mucus of spontaneous or induced ovulatory cycles. Steroids, 65(1):1-7,2000.

Anderson, R. A.; Feathergill, K. A.; Drisdel, R. C.; Rawlins, R. G.; Mack, S. R. & Zaneveld, L. J. Atrial natriuretic peptide (ANP) as a stimulus of the human acrosome reaction and a component of ovarian follicular fluid: correlation of follicular ANP content with in vitro fertilization outcome. J. Androl., 15(1):61-70, 1994.

Anderson, R. A. Jr.; Feathergill, K. A.; Rawlins, R. G.; Mack, S. R. & Zaneveld, L. J. Atrial natriuretic peptide: a chemoattractant of human spermatozoa by a guanylate cyclase-dependent pathway. Mol. Reprod. Dev., 40(3):371-8, 1995.

Aquila, S.; Sisci, D.; Gentile, M.; Middea, E.; Catalano, S.; Carpino, A.; Rago, V. & Andò, S. Estrogen receptor (ER)alpha and ER beta are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol3-OH kinase/Akt pathway. J. Clin. Endocrinol. Metab., 89(3):1443-51, 2004.

Ball, G. D.; Bellin, M. E.; Ax, R. L. & First, N. L. Glycosaminoglycans in bovine cumulus-oocyte complexes: morphology and chemistry. Mol. Cell. Endocrinol., 28(1):113–22, 1982.

Barros, C.; Argüello, B.; Jedlicki, A.; Vigil, P. & Herrera, E. Scanning electron microscope study of human cervical mucus. Gamete Res., 12(1):85-9, 1985.

Barros, C.; Vigil, P.; Herrera, E.; Arguello, B. & Walker, R., Selection of morphologically abnormal sperm by human cervical mucus. Arch. Androl., 12 Suppl:95–107, 1984.

Beebe, S. J.; Leyton, L.; Burks, D.; Ishikawa, M.; Fuerst, T.; Dean, J. & Saling, P. Recombinant mouse ZP3 inhibits sperm binding and induces the acrosome reaction. Dev. Biol., 151(1):48-54,1992.

von Bernhardi, R.; de Ioannes, A. E.; Blanco, L. P.; Herrera, E.; Bustos-Obregón, E. & Vigil, P. Round-headed spermatozoa: a model to study the role of the acrosome in early events of gamete interaction. Andrologia, 22(1):12-20, 1990.

Bianchi, P. G.; De Agostini, A.; Fournier, J.; Guidetti, C.; Tarozzi, N.; Bizzaro, D. & Manicardi, G. C. Human cervical mucus can act in vitro as a selective barrier against spermatozoa carrying fragmented DNA and chromatin structural abnormalities. J. Assist. Reprod. Genet., 21(4):97- 102, 2004.

Blackwell, L. F.; Vigil, P.; Cooke, D. G.; d’Arcangues, C. & Brown, J. B. Monitoring of ovarian activity by daily measurement of urinary excretion rates of oestrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part III: variability of normal menstrual cycle profiles. Hum. Reprod., 28(12):3306-15, 2013.

Bleil, J. D.; Greve, J. M. & Wassarman, P. M. Identification of a secondary sperm receptor in the mouse egg zona pellucida: role in maintenance of binding of acrosome-reacted sperm to eggs. Dev. Biol., 128(2):376-85, 1988.

Bleil, J. D. & Wassarman, P. M. Mammalian spermegg interaction: identification of a glycoprotein in mouse egg zonae pellucidae possessing receptor activity for sperm. Cell, 20(3):873-82, 1980.

Bradley, M. P. & Garbers, D. L. The stimulation of bovine caudal epididymal sperm forward motility by bovine cumulus-egg complexes in vitro. Biochem. Biophys. Res. Commun., 115(3):777-87, 1983.

Caballero-Campo, P.; Chirinos, M.; Fan, X. J.; González-González, M. E.; Galicia-Chavarría, M.; Larrea, F. & Gerton, G. L. Biological effects of recombinant human zona pellucida proteins on sperm function. Biol. Reprod., 74(4):760-8, 2006.

Ceric, F.; Silva, D. & Vigil, P. Ultrastructure of the human periovulatory cervical mucus. J. Electron Microsc. (Tokyo), 54(5):479-84, 2005.

Chakravarty, S.; Kadunganattil, S.; Bansal, P.; Sharma, R. K. & Gupta, S. K. Relevance of glycosylation of human zona pellucida glycoproteins for their binding to capacitated human spermatozoa and subsequent induction of acrosomal exocytosis. Mol. Reprod. Dev., 75(1):75-88, 2008.

Chiu, P. C.; Chung, M. K.; Koistinen, R.; Koistinen, H.; Seppala, M.; Ho, P. C.; Ng, E. H.; Lee, K. F. & Yeung, W. S. Glycodelin-A interacts with fucosyltransferase on human sperm plasma membrane to inhibit spermatozoa-zona pellucida binding. J. Cell Sci., 120(Pt. 1):33-44, 2006.

Chiu, P. C.; Lam, K. K.; Wong, R. C. & Yeung, W. S. The identity of zona pellucida receptor on spermatozoa: an unresolved issue in developmental biology. Semin. Cell Dev. Biol., 30:86-95, 2014.

Chiu, P. C.; Wong, B. S.; Lee, C. L.; Pang, R. T.; Lee, K. F.; Sumitro, S. B.; Gupta, S. K. & Yeung, W. S. Native human zona pellucida glycoproteins: purification and binding properties. Hum. Reprod., 23(6):1385-93, 2008a.

Chiu, P. C.; Wong, B. S.; Chung, M. K.; Lam, K. K.; Pang, R. T.; Lee, K. F.; Sumitro, S. B.; Gupta, S. K. & Yeung, W. S. Effects of native human zona pellucida glycoproteins 3 and 4 on acrosome reaction and zona pellucida binding of human spermatozoa. Biol. Reprod., 79(5):869-77, 2008b.

Cho, C.; Bunch, D. O.; Faure, J. E.; Goulding, E. H.; Eddy, E. M.; Primakoff, P. & Myles, D. G. Fertilization defects in sperm from mice lacking fertilin beta. Science, 281(5384):1857-9, 1998.

Chrétien, F. C. Involvement of the glycoproteic meshwork of cervical mucus in the mechanism of sperm orientation. Acta Obstet. Gynecol. Scand., 82(5):449-61, 2003.

Claw, K. G. & Swanson, W. J. Evolution of the egg: new findings and challenges. Annu. Rev. Genomics Hum. Genet., 13:109-25, 2012.

Coonrod, S.; Naaby-Hansen, S.; Shetty, J. & Herr, J. PI-PLC releases a 25-40 kDa protein cluster from the hamster oolemma and affects the sperm penetration assay. Mol. Hum. Reprod., 5(11):1027-33, 1999.

Cortés, M. E. Morphological and ultrastructural characterization of different types of bovine cervical mucus using light and scanning electron microscopy. Tesis de Doctorado en Ciencias de la Agricultura, Area Fisiología y Nutrición Animal. Santiago de Chile, Facultad de Agronomía e Ingeniería Forestal, Pontificia Universidad Católica de Chile, 2012.

Croxatto, H. B.; Ortiz, M. E. & Morales, P. Transporte ovular, migración espermática, fecundación, desarrollo preimplantacional y nidación. In: Pérez, A. & Donoso, E. (Eds.). Obstetricia. Santiago de Chile, Mediterráneo, 2011. pp.89-107.

Daunter, B.; Chantler, E. N. & Elstein, M. The scanning electronmicroscopy of human cervical mucus in the non-pregnant and pregnant states. Br. J. Obstet. Gynaecol., 83(9):738-43, 1976.

Demott, R. P. & Suarez, S. S. Hyperactivated sperm progress in the mouse oviduct. Biol. Reprod., 46(5):779-85, 1992.

Eggert-Kruse, W.; Reimann-Andersen, J.; Rohr, G.; Pohl, S.; Tilgen, W. & Runnebaum, B. Clinical relevance of sperm morphology assessment using strict criteria and relationship with spermmucus interaction in vivo and in vitro. Fertil. Steril., 63(3):612-24, 1995.

Ellington, J. E.; Ignotz, G. G.; Ball, B. A.; MeyersWallen, V. N. & Currie, W. B. De novo protein synthesis by bovine uterine tube (oviduct) epithelial cells changes during co-culture with bull spermatozoa. Biol. Reprod., 48(4):851-6,1993.

Erdö, S. L.; Villányi, P. & László, A. Gestational changes of GABA levels and GABA binding in the human uterus. Life Sci., 44(26):2009-14, 1989.

Familiari, G.; Relucenti, M.; Heyn, R.; Micara, G. & Correr, S. Three-dimensional structure of the zona pellucida at ovulation. Microsc. Res. Tech., 69(6):415-26, 2006.

Fazeli, A.; Affara, N. A.; Hubank, M. & Holt, W. V. Sperm-induced modification of the oviductal gene expression profile after natural insemination in mice. Biol. Reprod., 71(1):60-5, 2004.

Fetterolf, P. M.; Jurisicova, A.; Tyson, J. E. & Casper, R. F. Conditioned medium from human cumulus oophorus cells stimulates human sperm velocity. Biol. Reprod., 51(2):184-92, 1994.

Fléchon, J. E. & Hunter, R. H. Distribution of spermatozoa in the utero-tubal junction and isthmus of pigs, and their relationship with the luminal epithelium after mating: a scanning electron microscope study. Tissue Cell, 13(1):127-39, 1981.

Fredricsson, B. & Björk, G. Morphology of postcoital spermatozoa in the cervical secretion and its clinical significance. Fertil. Steril., 28(8):841-5, 1977.

Fusi, F. M.; Viganò, P.; Daverio, R.; Busacca, M. & Vignali, M. Effects of the coculture with human endometrial cells on the function of spermatozoa from subfertile men. Fertil. Steril., 61(1):160- 7, 1994.

Gaddum-Rosse, P. Mammalian gamete interactions: what can be gained from observations on living eggs? Am. J. Anat., 174(3):347-56, 1985.

Georgiou, A. S.; Snijders, A. P.; Sostaric, E.; Aflatoonian, R.; Vazquez, J. L., Vazquez, J. M.; Roca, J.; Martinez, E. A.; Wright, P. C. & Fazeli, A. Modulation of the oviductal environment by gametes. J. Proteome Res., 6(12):4656-66,2007.

Gerken, T. A. Biophysical approaches to salivary mucin structure, conformation and dynamics. Crit. Rev. Oral Biol. Med., 4(3-4):261-70, 1993.

Gipson, I. K.; Ho, S. B.; Spurr-Michaud, S. J.; Tisdale, A. S.; Zhan, Q.; Torlakovic, E.; Pudney, J.; Anderson, D. J.; Toribara, N. W. & Hill, J. A. 3rd. Mucin genes expressed by human female reproductive tract epithelia. Biol. Reprod., 56(4):999-1011, 1997.

Gipson, I. K.; Spurr-Michaud, S.; Moccia, R.; Zhan, Q.; Toribara, N.; Ho, S.B.; Gargiulo, A R. & Hill, J. A. 3rd. MUC4 and MUC5B transcripts are the prevalent mucin messenger ribonucleic acids of the human endocervix. Biol. Reprod., 60(1):58-64, 1999.

Gladkevich, A.; Korf, J.; Hakobyan, V. P. & Melkonyan, K. V. The peripheral GABAergic system as a target in endocrine disorders. Auton. Neurosci., 124(1-2):1-8, 2006.

Griendling, K. K.; Lassègue, B. & Alexander, R. W., Angiotensin receptors and their therapeutic implications. Annu. Rev. Pharmacol. Toxicol., 36:281-306, 1996.

Gupta, S. K. & Bhandari, B. Acrosome reaction: relevance of zona pellucida glycoproteins. Asian J. Androl., 13(1):97-105, 2011.

Gur, Y.; Breitbart, H.; Lax, Y.; Rubinstein, S. & Zamir, N. Angiotensin II induces acrosomal exocytosis in bovine spermatozoa. Am. J. Physiol., 275(1 Pt. 1):E87-93, 1998.

Gurevich, M.; Harel-Markowitz, E.; Marcus, S.; Shore, L. S. & Shemesh, M. Prostaglandin production by the oocyte cumulus complex around the time of fertilization and the effect of prostaglandin E on the development of the early bovine embryo. Reprod. Fertil. Dev., 5(3):281-3, 1993.

Hafez, E. S. Sperm Transport in the Human and Mammalian Cervix. In: Jordan, J. & Singer, A. (Eds.). The Cervix. London, The Whitefriars, 1976. pp.164-75.

Hanson, F. W. & Overstreet, J. W. The interaction of human spermatozoa with cervical mucus in vivo. Am. J. Obstet. Gynecol., 140(2):173-8, 1981.

Harper, M. J. K. Gamete and Zygote Transport. In: Knobil, E. & Neill, J. D. (Eds.). The Physiology of Reproduction. New York, Raven Press, 1994. pp.123-87.

Helm, G.; Owman, C.; Rosengren, E. & Sjöberg, N. O. Regional and cyclic variations in catecholamine concentration of the human fallopian tube. Biol. Reprod., 26(4):553-8, 1982.

Hunter, R. H. F. Physiology of the Graafian Follicle and Ovulation. Cambridge, Cambridge University Press, 2003.

Hunter, R. H. F. The Fallopian Tubes: Their Role in Fertility and Infertility. Berlin, Springer-Verlag, 1988.

Jaiswal, B. S.; Eisenbach, M. & Tur-Kaspa, I. Detection of partial and complete acrosome reaction in human spermatozoa: which inducers and probes to use? Mol. Hum. Reprod., 5(3):214-9, 1999.

Jansen, R. P. Cyclic changes in the human fallopian tube isthmus and their functional importance. Am. J. Obstet. Gynecol., 136(3):292-308, 1980.

Jiménez-Movilla, M.; Avilés, M.; Gómez-Torres, M. J.; Fernández-Colom, P. J.; Castells, M. T.; de Juan, J. & Romeu, A.; Ballesta, J. Carbohydrate analysis of the zona pellucida and cortical granules of human oocytes by means of ultrastructural cytochemistry. Hum. Reprod., 19(8):1842-55, 2004.

Katz, D. F.; Slade, D. A. & Nakajima, S. T. Analysis of pre-ovulatory changes in cervical mucus hydration and sperm penetrability. Adv. Contracept., 13(2-3):143-51, 1997.

Kohn, F. M.; Müller, C.; Drescher, D.; Neukamm, C.; el Mulla, K. F.; Henkel, R.; Hägele, W.; Hinsch, E.; Habenicht, U. F. & Schill, W. B., Effect of angiotensin converting enzyme (ACE) and angiotensins on human sperm functions. Andrologia, 30(4-5):207-15, 1998.

Kufe, D. W. Mucins in cancer: function, prognosis and therapy. Nat. Rev. Cancer, 9(12):874-85, 2009.

Lachance, C.; Bailey, J. L. & Leclerc, P. Expression of Hsp60 and Grp78 in the human endometrium and oviduct, and their effect on sperm functions. Hum. Reprod., 22(10):2606-14, 2007.

Laflamme, J.; Akoum, A. & Leclerc, P. Induction of human sperm capacitation and protein tyrosine phosphorylation by endometrial cells and interleukin-6. Mol. Hum. Reprod., 11(2):141- 50, 2005.

Lai, Y. M.; Chang, F. H.; Lee, C. L.; Lee, J. D.; Huang, H. Y.; Wang, M. L.; Chan, P. J.; Chang, M. Y. & Soong, Y. K. Coculture of human spermatozoa with reproductive tract cell monolayers can enhance sperm functions better than coculture with Vero cell monolayers. J. Assist. Reprod. Genet., 13(5):417-22, 1996.

Le Naour, F.; Rubinstein, E.; Jasmin, C.; Prenant, M. & Boucheix, C. Severely reduced female fertility in CD9-deficient mice. Science, 287(5451):319-21, 2000.

Leader, A.; Minuk, G.Y. & Mortimer, D. Seminal plasma gamma-aminobutyric acid (GABA) levels in normospermic men. Clin. Invest. Med., 15(4):346-8, 1992.

Lin, Y.; Mahan, K.; Lathrop, W. F.; Myles, D. G. & Primakoff, P. A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg. J. Cell Biol., 125(5):1157- 63, 1994.

Lopes, S.; Sun, J. G.; Jurisicova, A.; Meriano, J. & Casper, R. F. Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertil. Steril., 69(3):528-32, 1998.

Lucas, H.; Bercegeay, S.; Le Pendu, J.; Jean, M.; Mirallie, S. & Barriere, P. A fucose-containing epitope potentially involved in gamete interaction on the human zona pellucida. Hum. Reprod., 9(8):1532-8, 1994.

Luconi, M.; Francavilla, F.; Porazzi, I.; Macerola, B.; Forti, G. & Baldi, E. Human spermatozoa as a model for studyingmembrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids, 69(8- 9):553-9, 2004.

Mahi-Brown, C. A. & Yanagimachi, R. Parameters influencing ovum pickup by oviductal fimbria in the golden hamster. Gamete Res., 8(1):1-10, 1983.

Mattioli, M. Transduction mechanisms for gonadotrophin-induced oocyte maturation in mammals. Zygote, 2(4):347-9, 1994.

Miranda, P. V.; Gonzalez-Echeverría, F.; MarínBriggilers, C. I.; Brandelli, A.; Blaquier, J. A. & Tezo, J. G. Glycosidic residues involved in human sperm-zona pellucida binding in vitro. Mol. Hum. Reprod., 3(5):399-404, 1997.

Morales, P. Gonadotropin-releasing hormone increases ability of the spermatozoa to bind to the human zona pellucida. Biol. Reprod., 59(2):426-30, 1998.

Morales, P.; Roco, M. & Vigil, P. Human cervical mucus: relationship between biochemical characteristics and ability to allow migration of spermatozoa. Hum. Reprod., 8(1):78-83, 1993.

Mori, K.; Daitoh, T.; Irahara, M.; Kamada, M. & Aono, T. Significance of D-mannose as a sperm receptor site on the zona pellucida in human fertilization. Am. J. Obstet. Gynecol., 161(1):207-11, 1989.

Motta, P. & Van Blerkom, J. A scanning electron microscopic study of rabbit spermatozoa in the female reproductive tract following coitus. Cell Tissue Res., 163(1):29-44, 1975.

Murray, S. C. & Smith, T. T. Sperm interaction with fallopian tube apical membrane enhances sperm motility and delays capacitation. Fertil. Steril.,68(2):351-7, 1997.

Naz, R. K. & Kaplan, P. Increased levels of interleukin6 in seminal plasma of infertile men. J. Androl., 15(3):220-7, 1994a.

Naz, R. K. & Kaplan, P. Interleukin-6 enhances the fertilizing capacity of human sperm by increasing capacitation and acrosome reaction. J. Androl., 15(3):228-33, 1994b.

Nishimura, H.; Cho, C.; Branciforte, D. R.; Myles, D. G. & Primakoff, P. Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin beta. Dev. Biol., 233(1):204-13, 2001.

Oehninger, S.; Patankar, M.; Seppala, M. & Clark, G. F. Involvement of selectin-like carbohydrate binding specificity in human gamete interaction. Andrologia, 30(4-5):269-74, 1998.

Ong, J. & Kerr, D. I. GABA-receptors in peripheral tissues. Life Sci., 46(21):1489-501, 1990.

Pollard, J. W.; Plante, C.; King, W. A.; Hansen, P. J.; Betteridge, K. J. & Suarez, S. S. Fertilizing capacity of bovine sperm may be maintained by binding of oviductal epithelial cells. Biol. Reprod., 44(1):102- 7, 1991.

Potter, L. R.; Yoder, A. R.; Flora, D. R.; Antos, L. K. & Dickey, D. M. Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb. Exp. Pharmacol., (191):341- 66, 2009.

Qiu, J.; Hales, B. F. & Robaire, B. Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure. Biol. Reprod., 53(6):1465-73, 1995a.

Qiu, J.; Hales, B. F. & Robaire, B. Effects of chronic low-dose cyclophosphamide exposure on the nuclei of rat spermatozoa. Biol. Reprod., 52(1):33- 40, 1995b.

Ralt, D.; Goldenberg, M., Fetterolf, P.; Thompson, D.; Dor, J.; Mashiach, S.; Garbers, D. L. & Eisenbach, M. Sperm attraction to a follicular factor(s) correlates with human egg fertilizability. Proc. Natl. Acad. Sci. U. S. A., 88(7):2840-4, 1991.

Rotem, R.; Zamir, N.; Keynan, N.; Barkan, D.; Breitbart, H. & Naor, Z. Atrial natriuretic peptide induces acrosomal exocytosis of human spermatozoa. Am. J. Physiol., 274(2 Pt. 1):E218-23, 1998.

Rubinstein, E.; Ziyyat, A.; Prenant, M.; Wrobel, E.; Wolf, J. P.; Levy, S.; Le Naour, F. & Boucheix, C. Reduced fertility of female mice lacking CD81.Dev. Biol., 290(2):351-8, 2006.

Sabeur, K.; Vo, A. T. & Ball, B. A. Effects of angiotensin II on the acrosome reaction in equine spermatozoa. J. Reprod. Fertil., 120(1):135-42, 2000.

Sakkas, D.; Urner, F.; Bianchi, P. G.; Bizzaro, D.; Wagner, I.; Jaquenoud, N.; Manicardi, G. & Campana, A. Sperm chromatin anomalies can influence decondensation after intracytoplasmic sperm injection. Hum. Reprod., 11(4):837-43, 1996.

Sheehan, J. K. & Carlstedt, I. Electron microscopy of cervical-mucus glycoproteins and fragments therefrom. The use of colloidal gold to make visible 'naked' protein regions. Biochem. J., 265(1):169-77, 1990.

Shi, Q. X.; Yuan, Y. Y. & Roldan, E. R. gammaAminobutyric acid (GABA) induces the acrosome reaction in human spermatozoa. Mol. Hum. Reprod., 3(8):677-83, 1997.

Shivaji, S. & Jagannadham, M. V. Steroid-induced perturbations of membranes and its relevance to sperm acrosome reaction. Biochim. Biophys. Acta, 1108(1):99-109, 1992.

Suarez, S.; Redfern, K.; Raynor, P.; Martin, F. & Phillips, D. M. Attachment of boar sperm to mucosal explants of oviduct in vitro: possible role in formation of a sperm reservoir. Biol. Reprod., 44(6):998-1004, 1991.

Suarez, S. S. Regulation of sperm storage and movement in the mammalian oviduct. Int. J. Dev. Biol., 52(5-6):455-62, 2008.

Tabibzadeh, S.; Kong, Q. F.; Babaknia, A. & May, L. T. Progressive rise in the expression of interleukin6 in human endometrium during menstrual cycle is initiated during the implantation window. Hum. Reprod., 10(10):2793-9, 1995.

Tamba, S.; Yodoi, R.; Segi-Nishida, E.; Ichikawa, A.; Narumiya, S. & Sugimoto, Y. Timely interaction between prostaglandin and chemokine signaling is a prerequisite for successful fertilization. Proc. Natl. Acad. Sci. U. S. A., 105(38):14539-44, 2008.

Teissier, M. P.; Chable, H.; Paulhac, S. & Aubard, Y. Comparison of follicle steroidogenesis from normal and polycystic ovaries in women undergoing IVF: relationship between steroid concentrations, follicle size, oocyte quality and fecundability. Hum. Reprod., 15(12):2471-7, 2000.

Tesarik, J.; Mendoza Oltras, C. & Testart, J. Effect of the human cumulus oophorus on movement characteristics of human capacitated spermatozoa. J. Reprod. Fertil., 88(2):665-75, 1990.

Turner, K. O. & Meizel, S. Progesterone-mediated efflux of cytosolic chloride during the human sperm acrosome reaction. Biochem. Biophys. Res. Commun., 213(3):774-80, 1995.

Urra, J. A.; Villaroel-Espíndola, F.; Covarrubias, A. A.; Rodríguez-Gil, J. E.; Ramírez-Reveco, A. & Concha, I. I. Presence and function of dopamine transporter (DAT) in stallion sperm: dopamine modulates sperm motility and acrosomal integrity. PloS One, 9(11):e112834, 2014.

Vandermolen, D. T. & Gu, Y. Human endometrial interleukin-6 (IL-6): in vivo messenger ribonucleic acid expression, in vitro protein production, and stimulation thereof by IL-1 beta. Fertil. Steril., 66(5):741-7, 1996.

Viggiano, J. M.; Herrero, M. B.; Cebral, E.; Boquet, M. G. & de Gimeno, M. F. Prostaglandin synthesis by cumulus-oocyte complexes: effects on in vitro fertilization in mice. Prostaglandins Leukot. Essent. Fatty Acids, 53(4):261-5, 1995.

Vigil, P. Gamete membrane fusion in hamster spermatozoa with reacted equatorial segment. Gamete Res., 23(2):203-13, 1989.

Vigil, P.; Barrientos, V. M.; Vargas, G. G.; Machuca, D. A. & Cortés, M. E. Assessment of the effect of testosterone on the acrosome reaction of human spermatozoa. Andrologia, 44 Suppl. 1:627-33, 2012a.

Vigil, P. & Bustos-Obregon, E. Alkylating agents and mouse spermatogenesis: effects of a single dose of cyclophosphamide. Andrologia, 17(3):276-82, 1985.

Vigil, P.; Cortés, M. E.; Zúñiga, A.; Riquelme, J. & Ceric, F. Scanning electron and light microscopy study of the cervical mucus in women with polycystic ovary syndrome. J. Electron. Microsc. (Tokyo), 58(1):21-7, 2009.

Vigil, P.; Perez, A.; Neira, J. & Morales, P. Post-partum cervical mucus: biological and rheological properties. Hum. Reprod., 6(4):475-9, 1991.

Vigil, P.; Riquelme, R. & Morales, P. Sperm binding to the human zona pellucida after migration through human cervical mucus. Int. J. Androl., 18 Suppl. 1:7-11, 1995.

Vigil, P.; Rubio, V.; Prado, S.; Socías, T.; Salgado, A. M. & Morales, P. Migration of human sperm through the Fallopian tube in vitro. In: Rodríguez-Armas, O.; Baumgartner, W. & Burgos-Briceño, L. (Eds.). Fertility and sterility progress in research and practice: The proceedings of the XIV World Congress on Fertility and Sterility. Caracas, Parthenon Publication Group, 1994. Pp.19-30.

Vigil, P.; Salgado, A. M. & Cortés, M. E. Ultrastructural interaction between spermatozoon and human oviductal cells in vitro. J. Electron. Microsc. (Tokyo), 61(2):123-6, 2012b.

Vigil, P.; Toro, A. & Godoy, A. Physiological action of oestradiol on the acrosome reaction in human spermatozoa. Andrologia, 40(3):146-51, 2008.

Vigil P.; Cortés M. E.; Carrera B.; Hauyón R.; Aravena, C. El moco cervical en la fisiología reproductiva. In: Guzmán, E.; Croxatto, H. & Lalonde, A. (Eds.). Selección en Temas de Ginecoobstetricia. Tomo III. Santiago de Chile, Ediciones Publiimpacto, 2014. pp.325-34.

Vigil, P. La fertilidad de la pareja humana. 4a ed. Santiago de Chile, Ediciones Universidad Catolica, 2013. pp.76-7.

Wassarman, P. M. The mammalian ovum. In: Knobil, E. & Neill, J. (Eds.). The physiology of reproduction. New York, Raven Press, 1988. pp.69-102.

Wassarman, P. M.; Jovine, L. & Litscher, E. S. A profile of fertilization in mammals. Nat. Cell. Biol., 3(2):E59-64, 2001.

Wassarman, P. M. & Litscher, E. S. Mammalian fertilization: the egg's multifunctional zona pellucida. Int. J. Dev. Biol., 52(5-6):665-76,2008.

Way, A. L.; Barbato, G. F. & Killian, G. J. Identification of norepinephrine in bovine oviductal fluid by high performance liquid chromatography. Life Sci., 70(5):567-76, 2001.

Way, A. L. & Killian, G. J. Capacitation and induction of the acrosome reaction in bull spermatozoa with norepinephrine. J. Androl., 23(3):352-7, 2002.

Westphal, L. M.; el Dansasouri, I.; Shimizu, S.; Tadir, Y. & Berns, M. W. Exposure of human spermatozoa to the cumulus oophorus results in increased relative force as measured by a 760 nm laser optical trap. Hum. Reprod., 8(7):1083-6, 1993.

von Wolff, M.; Thaler, C. J.; Zepf, C.; Becker, V.;Beier, H. M. & Strowitzki, T. Endometrial expression and secretion of interleukin-6 throughout the menstrual cycle. Gynecol. Endocrinol., 16(2):121-9, 2002.

Yanagimachi, R. Fertility of mammalian spermatozoa: its development and relativity. Zygote, 2(4):371- 2, 1994.

Yeung, W. S.; Lee, K. F.; Koistinen, R.; Koistinen, H.;Seppälä, M. & Chiu, P. C. Effects of glycodelins on functional competence of spermatozoa. J. Reprod. Immunol., 83(1-2):26-30, 2009.

Ying, S.; Ling, N.; Böhlen, P. & Guillemin, R. Gonadocrinins: peptides in ovarian follicular fluid stimulating the secretion of pituitary gonadotropins. Endocrinology, 108(4):1206-15,1981.

Yudin, A. I.; Cherr, G. N. & Katz, D. F. Structure of the cumulus matrix and zona pellucida in the golden hamster: a new view of sperm interaction with oocyte-associated extracellular matrices. Cell Tissue Res., 251(3):555-64, 1988.

Zhang, M.; Hong, H.; Zhou, B.; Jin, S.; Wang, C.; Fu, M.; Wang, S. & Xia, G. The expression of atrial natriuretic peptide in the oviduct and its functions in pig spermatozoa. J. Endocrinol., 189(3):493- 507, 2006.

Zumoffen, C. M.; Caille, A. M.; Munuce, M. J.; Cabada, M. O. & Ghersevich, S. A. Proteins from human oviductal tissue-conditioned medium modulate sperm capacitation. Hum. Reprod., 25(6):1504- 12, 2010.