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Non-genomic regulation and disruption of spermatozoal in vitro hyperactivation by oviductal hormones

Abstract

During capacitation, motility of mammalian spermatozoon is changed from a state of “activation” to “hyperactivation.” Recently, it has been suggested that some hormones present in the oviduct are involved in the regulation of this hyperactivation in vitro. Progesterone, melatonin, and serotonin enhance hyperactivation through specific membrane receptors, and 17β-estradiol suppresses this enhancement by progesterone and melatonin via a membrane estrogen receptor. Moreover, γ-aminobutyric acid suppresses progesterone-enhanced hyperactivation through the γ-aminobutyric acid receptor. These hormones dose-dependently affect hyperactivation. Although the complete signaling pathway is not clear, progesterone activates phospholipase C and protein kinases and enhances tyrosine phosphorylation. Moreover, tyrosine phosphorylation is suppressed by 17β-estradiol. This regulation of spermatozoal hyperactivation by steroids is also disrupted by diethylstilbestrol. The in vitro experiments reviewed here suggest that mammalian spermatozoa are able to respond to effects of oviductal hormones. We therefore assume that the enhancement of spermatozoal hyperactivation is also regulated by oviductal hormones in vivo.

Introduction

In the oviduct, mammalian spermatozoa fertilize the oocyte. Before fertilization, however, spermatozoa must be capacitated [14]. Capacitation is a qualitative change in the spermatozoa that is needed for fertilization of the oocyte. Capacitated spermatozoa exhibit two reactions associated with capacitation. One is an acrosome reaction that occurs at the head of a spermatozoon. This reaction is a specialized exocytosis that is required for penetration of the zona pellucida (ZP) and for binding to the oocyte [1, 2, 4, 5]. The other is hyperactivation that occurs at the flagellum. Hyperactivation induces a specialized flagellar movement that creates the driving force for swimming in the oviduct and for penetrating the ZP [14]. Moreover, it has been shown that the ability of spermatozoon to be hyperactivated correlates with the success of in vitro fertilization [6].

By use of a specific culture medium, capacitation is also made to occur in vitro. During in vitro capacitation, spermatozoa show motility change, such as from “activation” to “hyperactivation.” Just after swim up in a specific culture medium, spermatozoa are activated (movies 1, 3, and 5). In many animals, activated spermatozoa show a small bend amplitude in flagellar movement and swim linearly. After incubation for some hours (for example, 3–4 h in hamster and mouse spermatozoa and 4–5 h in rat spermatozoa), most spermatozoa show hyperactivated motility (movies 2, 4, and 6). However, the movement pattern of hyperactivated spermatozoon basically depends on animals [1]. In hamster and mouse (movies 2 and 4), hyperactivated spermatozoa show a large amplitude and a large asymmetric beating pattern in flagellar movement. Sometimes, their spermatozoa writhe and swim in the form of eight characters. In rat spermatozoa (movie 6), many hyperactivated spermatozoa show the large amplitude of head, the arched movement of middle peace of flagellum, and the decrease of progressive movement although identification of their movement pattern is difficult.

During spermatozoal capacitation, hyperactivation occurs spontaneously and time-dependently [13, 79]. The first stimulation for capacitation/hyperactivation is the removal of cholesterol from a spermatozoal plasma membrane by albumin [1013]. The next step is Ca2+ influx and cAMP production stimulated by HCO3 . Stimulation by Ca2+ and HCO3 activates certain protein kinases and phosphorylates proteins [1419]. Additionally, the suppression of protein phosphatases induces hyperactivation and protein phosphorylation [20]. Tyrosine phosphorylation is well known as a capacitation-associated intracellular signal [14, 15, 19]. The most popular tyrosine phosphorylation molecule is an 80-kDa protein, which was identified as an A-kinase anchoring protein (AKAP) [21]. These stimulations and signal transductions are associated with regulation of capacitation, and induce the acrosome reaction and hyperactivation.

After the 1980s, it has been reported that several molecules that are found from the oviductal and follicular fluids affect spermatozoal acrosome reaction and hyperactivation [1113, 2239]. Progesterone and serotonin are well-known classical effectors of the acrosome reaction [22, 40]. Recently, it has been suggested that progesterone, melatonin, and serotonin act as inducers or enhancers of the acrosome reaction and hyperactivation [1113, 2931, 33], and that 17β-estradiol acts as a suppressor for these processes [32, 34]. Moreover, it has been reported that γ-aminobutyric acid (GABA) acts as an inducer of the acrosome reaction and hyperactivation in humans, rams, and rats [3538], although it acts as a suppressor of hyperactivation in hamsters [39]. In the present article, we review effects of the above molecules on hyperactivation.

Non-genomic regulation of hyperactivation by progesterone

Progesterone was found to be an inducer of the acrosome reaction in human follicular fluid [22]. Additionally, in hamsters, 20 ng/ml of progesterone increased ZP penetration and enhanced hyperactivation [11, 25]. In hamsters, moreover, the concentration of progesterone was 4.2–7.4 μg/ml in the follicular fluid, and was 44.04–175.06 ng/ml in the oviductal fluid [41]. Therefore, it seems that the progesterone present in the follicular fluid induces the acrosome reaction and that the progesterone present in the oviductal fluid increases ZP penetration and enhances hyperactivation. Although progesterone regulates cell functions through genomic signals in somatic cells, it regulates the acrosome reaction, ZP penetration, and hyperactivation through non-genomic regulation in mammalian spermatozoa [23, 24, 30, 42]. In human spermatozoa, progesterone stimulates an influx of Ca2+ associated with CatSper activation, tyrosine phosphorylation, chloride efflux, and cAMP increase, and subsequently induces the acrosome reaction and hyperactivation [24, 30, 4245]. In hamster spermatozoa, progesterone enhances hyperactivation together with tyrosine phosphorylation [11]. Although the traditional genomic progesterone receptor (PR) does not exist in spermatozoa, a novel non-genomic PR exists at the plasma membrane of spermatozoa [23, 24, 27, 28, 42]. Moreover, it has been suggested that progesterone binds to the acrosome region where PR are localized in human and hamster spermatozoa [11, 46]. Downstream of the spermatozoal PR, phospholipase C (PLC) [47] and/or protein kinase A (PKA) [48] are involved in the progesterone-induced acrosome reaction in mouse and human spermatozoa. In hamster spermatozoa, PLC, PKA, and protein kinase C (PKC) are involved in the progesterone-enhanced hyperactivation downstream of the PR [11, 49].

It is well known that tyrosine phosphorylation sites, including AKAP, are associated with the regulation of spermatozoal capacitation/hyperactivation [1, 2, 14, 15, 19]. In several cases [11, 20], tyrosine phosphorylation is enhanced when spermatozoal hyperactivation is induced by molecules present in the oviduct. Although it is not clear which kinases cause tyrosine phosphorylation of spermatozoal proteins, it has been reported that tyrosine phosphorylation is regulated through Ca2+ signals associated with an inositol 1,4,5-tris–phosphate (IP3) receptor-gated Ca2+ store located at the base of the flagellum and calmodulin-dependent protein kinase [7, 9, 16, 17, 50]. Moreover, it has also been reported that tyrosine phosphorylation is regulated through cAMP-PKA signals [1, 14, 15, 19]. Because PLC, IP3 receptor, PKA, and PKC are involved in enhancement of hyperactivation in hamster spermatozoa [11, 49], it seems that progesterone enhances spermatozoal hyperactivation through binding to PR and activation of PLC. This binding results in the production of IP3 and diacylglycerol, release of intracellular Ca2+ from an IP3 receptor-gated Ca2+ store, activation of PKC, activation of adenylate cyclase, production of cAMP, activation of PKA, and enhancement of tyrosine phosphorylation (Fig. 1).

Fig. 1
figure1

Hypothesized mechanism for the regulation of hyperactivation enhancement by progesterone and estradiol. AC adenylate cyclase, ATP adenosine triphosphate, CAMK calmodulin-dependent protein kinase, cAMP cyclic adenosine monophosphate, DAG diacylglycerol, E estradiol, ER estrogen receptor, IP 3 inositol 1,4,5-tris–phosphate, IP 3 R inositol 1,4,5-tris–phosphate receptor, P progesterone, PC phosphatidylcholine, PI phosphatidylinositol, PKA protein kinase A, PKC protein kinase C, PLC phospholipase C, PR progesterone receptor, PTK protein tyrosine kinase

Suppression of progesterone-enhanced hyperactivation by 17β-estradiol

In human spermatozoa, it has been reported that 17β-estradiol suppresses the progesterone-induced acrosome reaction through non-genomic regulation associated with membrane estrogen receptor (ER) [24, 2931]. Although the detailed suppressive mechanism of 17β-estradiol is not clear, differences in Ca2+ influx due to progesterone and 17β-estradiol are considered important [29, 31]. The progesterone spike follows that of Ca2+ in spermatozoa, whereas 17β-estradiol gradually increases the intracellular Ca2+ concentration in spermatozoa [29, 31].

In hamster spermatozoa [32, 51], 17β-estradiol has been shown to suppress progesterone-enhanced hyperactivation through ER-inhibiting tyrosine phosphorylation (Fig. 1). Because the ER is present in the plasma membrane at the head of hamster spermatozoa [32], it seems that 17β-estradiol suppresses progesterone-enhanced hyperactivation through non-genomic regulation (Fig. 1). Suppression of progesterone-enhanced hyperactivation by 17β-estradiol occurs in a dose-dependent manner [32, 51]. The effect of 20 ng/ml of progesterone is suppressed by >20 pg/ml of 17β-estradiol. It seems that spermatozoal hyperactivation is regulated by the balance of progesterone and 17β-estradiol concentrations. Because the concentrations of progesterone and 17β-estradiol vary during the female estrous cycle [4], it seems that mammalian spermatozoa (at least hamster spermatozoa) are hyperactivated in response to progesterone and 17β-estradiol changes in the oviduct [8, 32, 51].

Disruption of the effects of steroids on hyperactivation by diethylstilbestrol (DES)

Diethylstilbestrol (DES) is an endocrine-disrupting chemical that affects some reproductive systems [52, 53]. Although it had not previously been known whether DES affects gametic function, a recent study [51] has suggested that DES affects the non-genomic regulation of hyperactivation by progesterone and 17β-estradiol. The effect of DES alone on progesterone-enhanced hyperactivation is very weak [51]. However, when spermatozoa are exposed to DES together with 17β-estradiol, DES suppresses progesterone-enhanced hyperactivation by accelerating the effect of 17β-estradiol [51]. Specifically, 20 pg/ml of 17β-estradiol with 20 pg/ml of DES was found to significantly suppress enhancement of hyperactivation by 20 ng/ml of progesterone, while 20 pg/ml of 17β-estradiol alone did not significantly suppress enhancement by 20 ng/ml of progesterone [51]. It seems that the effects of DES described above disrupt hyperactivation of hamster spermatozoa through non-genomic regulation associated with progesterone and 17β-estradiol.

Interaction between steroids and other molecules

Melatonin is an enhancer of spermatozoal hyperactivation [12, 33]. In hamsters, it has been shown that melatonin enhances spermatozoal hyperactivation via melatonin receptor type 1 [12]. In rams and humans, it has been shown that melatonin increases some spermatozoal functions (e.g., motility, capacitation, fertility rate, antioxidant enzyme activity) through decreasing nitric oxide (NO) [33, 5457]. Although low concentrations of NO induce capacitation through a mitogen-activated protein kinase cascade [5863], high concentrations of NO suppress spermatozoal functions [59, 61]. Generally, melatonin indirectly suppresses the reproductive system (e.g., steroidogenesis and spermatogenesis) through the central nervous system in seasonal breeding animals [4, 62, 63]. In contrast, melatonin directly affects spermatozoal functions of seasonal breeding animals and human [12, 33, 5457]. Moreover, a very recent study [34] has shown that 17β-estradiol suppresses melatonin-enhanced hyperactivation in hamster spermatozoa. The effect of melatonin and 17β-estradiol interaction on hyperactivation of hamster spermatozoa is direct, although the mechanisms behind this interaction are not at all clear.

Serotonin is also an enhancer of hyperactivation of hamster spermatozoa [13]. Low concentrations of serotonin enhance spermatozoal hyperactivation through the 5-HT2 receptor, whereas high concentrations of serotonin enhance hyperactivation through the 5-HT4 receptor. Serotonin also induces the acrosome reaction through the 5-HT2 and 5-HT4 receptors in hamster spermatozoa [40]. Generally, 5-HT2 receptor and 5-HT4 receptors activate PLC-Ca2+ signaling and adenylate cyclase-cAMP signaling, respectively [64, 65]. Although serotonin signals are similar to progesterone signals, it is not clear whether estradiol suppresses serotonin-enhanced hyperactivation as it does in the case of progesterone.

GABA induces the acrosome reaction and hyperactivation through GABA receptors in human, ram, and rat spermatozoa [3538]. In several cases, the GABAA receptor has been shown to be involved in inducing the acrosome reaction and hyperactivation [37, 38]. Although the GABAB receptor also exists in rat spermatozoa and is localized in the sperm head [6668], it is unclear whether the GABAB receptor is involved in spermatozoal functions. Interestingly, several studies have reported that progesterone induces the acrosome reaction and hyperactivation through the GABAA receptor in human, ram, and rat spermatozoa [3538], although many studies have reported that progesterone induces and enhances the acrosome reaction and hyperactivation through PR instead [11, 2224, 2628, 46, 48]. In contrast, in hamster spermatozoa, GABA suppresses progesterone-enhanced hyperactivation through the GABAA receptor [39]. Because the concentration of GABA in the oviduct is more than 2.5-fold that in the brain [69] and the concentration of GABA changes in the female genital tract through the estrous cycle [70], it is likely that GABA is involved in the regulation of capacitation in a similar manner to 17β-estradiol, including regulation of the acrosome reaction and hyperactivation. However, the detailed mechanisms behind GABA actions in spermatozoal capacitation are not yet clarified. Additionally, effects of GABA and GABAA receptor on spermatozoal functions confuse.

Conclusions

Rodent spermatozoa begin to be capacitated after moving into the oviduct. Other many mammalian (including human) spermatozoa present in the oviduct are capacitated. Capacitation-related events (acrosome reaction and hyperactivation), which occurred in a specialized culture medium in vitro, are regulated by molecules present in the oviduct, including progesterone, 17β-estradiol, melatonin, serotonin, and GABA. These molecules induce the acrosome reaction and hyperactivation of mammalian spermatozoa in a dose-dependent manner.

In vitro effects of these molecules on the acrosome reaction and hyperactivation should be confirmed as in vivo effects by in vivo experiments, although observations of effects of the molecules on spermatozoal acrosome reaction and hyperactivation in vivo are very difficult. At least, previous in vitro experiments suggested that mammalian spermatozoa were able to respond to effects of the molecules. Therefore, we consider that mammalian spermatozoa have abilities to respond to influences of the molecules in vivo. Because the concentrations of the molecules present in the oviduct vary during the estrous cycle [4], it seems that mammalian spermatozoa are acrosome-reacted and hyperactivated in response to the changing environment of the oviduct such as the changing concentration of the oviductal molecules [8, 11, 24, 25, 2932, 51]. Moreover, it seems that regulation of hyperactivation by molecules present in the oviduct, especially progesterone and 17β-estradiol, is unstable because this regulation is easily disrupted by DES accelerating the effect of 17β-estradiol [11, 25, 32, 51].

After beginning to swim, mammalian spermatozoa spontaneously are capacitated in the oviduct in order to be hyperactivated and finally acrosome-reacted. Based on the in vitro experiments reviewed here, we consider that the enhancement of spermatozoal hyperactivation is regulated through ligand-dependent mechanisms associated with oviductal molecules during capacitation. Moreover, we assume that its regulatory mechanisms are associated with changes in the oviduct environment because changes of concentration of oviductal molecules are involved in estrous cycle.

References

  1. 1.

    Yanagimachi R (1994) Mammalian fertilization. In: Knobil E, Neill JD (eds) The physiology of reproduction, vol 1, 2nd edn. Raven Press, New York

    Google Scholar 

  2. 2.

    Fujinoki M (2009) Non-genomic regulation of mammalian sperm hyperactivation. Reprod Med Biol 8:47–52

    CAS  Article  Google Scholar 

  3. 3.

    Mohri H, Inaba K, Ishijima S, Baba SA (2012) Tubulin-dynein system in flagellar and ciliary movement. Proc Jpn Acad Ser B 88:397–415

    CAS  Article  Google Scholar 

  4. 4.

    Schillo KK (2009) Reproductive physiology of mammals: from farm to field and beyond. Delmar, New York

    Google Scholar 

  5. 5.

    Yudin AI, Gottlieb W, Meizel S (1988) Ultrastructural studies of the early events of the human sperm acrosome reaction as initiated by human follicular fluid. Gamete Res 20:11–24

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Alasmari W, Barratt CLR, Publicover SJ, Whalley KM, Foster E, Kay V, da Silve SM, Oxenham SK (2013) The clinical significance of calcium-signaling pathways mediating human sperm hyperactivation. Hum Reprod 28:866–876

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Suarez SS, Ho HC (2003) Hyperactivated motility in sperm. Reprod Domest Anim 38:119–124

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Coy P, García-Vázquez FA, Visconti PE, Avilés M (2012) Roles of the oviduct in mammalian fertilization. Reproduction 144:649–660

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Ho HC, Suarez SS (2001) Hyperactivation of mammalian spermatozoa: function and regulation. Reproduction 122:519–526

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Langlais J, Roberts KD (1985) A molecular membrane model of sperm capacitation and the acrosome reaction of mammalian spermatozoa. Gamete Res 13:183–224

    Article  Google Scholar 

  11. 11.

    Noguchi T, Fujinoki M, Kitazawa M, Inaba N (2008) Regulation of hyperactivation of hamster spermatozoa by progesterone. Reprod Med Biol 7:63–74

    CAS  Article  Google Scholar 

  12. 12.

    Fujinoki M (2008) Melatonin-enhanced hyperactivation of hamster sperm. Reproduction 136:533–541

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Fujinoki M (2011) Serotonin-enhanced hyperactivation of hamster sperm. Reproduction 142:255–266

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Visconti PE, Kopf GS (1998) Regulation of protein phosphorylation during sperm capacitation. Biol Reprod 59:1–6

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Visconti PE, Galantino-Homer H, Ning X, Fornes MW, Moore GD, Bailey JL, Kopf GS (1998) The molecular basis of capacitation. J Androl 19:242–248

    CAS  PubMed  Google Scholar 

  16. 16.

    Ho HC, Suarez SS (2001) An inositol 1,4,5-trisphoshate receptor-gated intracellular Ca2+ store is involved in regulating sperm hyperactivated motility. Biol Reprod 65:1606–1616

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Ho HC, Granish KA, Suarez SS (2002) Hyperactivated motility of bull sperm is triggered at the axoneme by Ca2+ and not cAMP. Dev Biol 250:208–217

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Okamura N, Tajima Y, Soejima A, Masuda H, Sugita Y (1985) Sodium bicarbonate in seminal plasma stimulates the motility of mammalian spermatozoa through the direct activation of adenylate cyclase. J Biol Chem 260:9699–9705

    CAS  PubMed  Google Scholar 

  19. 19.

    Fujinoki M, Suzuki T, Takayama T, Shibahara H, Ohtake H (2006) Profiling of proteins phosphorylated or dephosphorylated during hyperactivation on hamster spermatozoa. Reprod Med Biol 5:123–135

    CAS  Google Scholar 

  20. 20.

    Suzuki T, Fujinoki M, Shibahara H, Suzuki M (2010) Regulation of hyperactivation by PPP2 in hamster spermatozoa. Reproduction 139:847–856

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Carrera A, Gerton GL, Moss SB (1994) The major fibrous sheath polypeptide of mouse sperm: structural and functional similarities to the A-kinase anchoring proteins. Dev Biol 165:272–284

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Osman RA, Andria ML, Jones AD, Meizel S (1989) Steroid induced exocytosis: the human sperm acrosome reaction. Biochem Biophys Res Commun 160:828–833

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Baldi E, Luconi M, Bonaccorsi L, Forti G (1998) Nongenomic effects of progesterone on spermatozoa: mechanisms of signal transduction and clinical implications. Front Biosci 3:1051–1059

    Google Scholar 

  24. 24.

    Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi E (2004) Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids 69:553–559

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Libersky EA, Boatman DE (1995) Effects of progesterone on in vitro sperm capacitation and egg penetration in the golden hamster. Biol Reprod 53:483–487

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Llanos MN, Anabalon MC (1996) Studies related to progesterone-induced hamster sperm acrosome reaction. Mol Reprod Dev 45:313–319

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Sabeur K, Edwards DP, Meizel S (1996) Human sperm plasma membrane progesterone receptor(s) and the acrosome reaction. Biol Reprod 54:993–1001

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Jang S, Yi LSH (2005) Identification of a 71-kDa protein as a putative non-genomic membrane progesterone receptor in boar spermatozoa. J Endocrinol 184:417–425

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Baldi E, Luconi M, Muratori M, Forti G (2000) A novel functional estrogen receptor on human sperm membrane interferes with progesterone effects. Mol Cell Endocrinol 161:31–35

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Baldi E, Luconi M, Muratori M, Marchiani S, Tamburrino L, Forti G (2009) Nongenomic activation of spermatozoa by steroid hormones: facts and fictions. Mol Cell Endocrinol 308:39–46

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Luconi M, Muratori M, Forti G, Baldi E (1999) Identification and characterization of a novel functional estrogen receptor on human sperm membrane that interferes with progesterone effects. J Clin Endocrinol Metabol 84:1670–1678

    CAS  Article  Google Scholar 

  32. 32.

    Fujinoki M (2010) Suppression of progesterone enhanced hyperactivation in hamster spermatozoa by estrogen. Reproduction 140:453–464

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    du Plessis SS, Hagenaar K, Lampiao F (2010) The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROS. Andrologia 42:112–116

    Article  PubMed  Google Scholar 

  34. 34.

    Fujinoki M, Takei GL (2015) Estrogen suppresses melatonin-enhanced hyperactivation of hamster spermatozoa. J Reprd Dev 61:287–295

    Article  Google Scholar 

  35. 35.

    Calogero AE, Hall J, Fishel S, Green S, Hunter A, D’Agata R (1996) Effects of γ-aminobutyric acid on human sperm motility and hyperactivation. Mol Hum Reprod 2:733–738

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    de las Heras MA, Valcarcel A, Perez LJ (1997) In vitro capacitating effect of gamma-aminobutyric acid in ram spermatozoa. Biol Reprod 56:964–968

    Article  PubMed  Google Scholar 

  37. 37.

    Ritta MN, Calamera JC, Bas DE (1998) Occurrence of GABA and GABA receptors in human spermatozoa. Mol Hum Reprod 4:769–773

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Jin J-Y, Chen W-Y, Zhou CX, Chen Z-H, Yuan Y-Y, Ni Y, Chan HC, Shi Q-X (2009) Activation of GABAA receptor/Cl channel and capacitation in rat spermatozoa: HCO3 and Cl are essential. Syst Biol Reprod Med 55:97–108

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Kon H, Takei GL, Fujinoki M, Shinoda M (2014) Suppression of progesterone-enhanced hyperactivation in hamster spermatozoa by γ-aminobutyric acid. J Reprod Dev 60:202–209

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Meizel S, Turner KO (1983) Serotonin or its agonist 5-methoxytryptamine can stimulate hamster sperm acrosome reactions in a more direct manner than catecholamines. J Exp Zool 226:171–174

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Libersky EA, Boatman DE (1995) Progesterone concentration in serum, follicular fluid, and oviductal fluid of the golden hamster during the periovulatory period. Biol Reprod 53:477–482

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Lösel R, Wehling M (2003) Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol 4:46–56

    Article  PubMed  Google Scholar 

  43. 43.

    Harper CV, Barratt CLR, Publicover SJ (2004) Stimulation of human spermatozoa with progesterone gradients to stimulate approach to the oocyte. J Biol Chem 279:46315–46325

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Lishko PV, Botchkina IL, Kirichok Y (2011) Progesterone activates the principal Ca2+ channel of human sperm. Nature 471:387–391

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Strünker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R, Kaupp UB (2011) The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm. Nature 471:382–386

    Article  PubMed  Google Scholar 

  46. 46.

    Gadkar S, Shah CA, Sachdeva G, Samant U, Puri CP (2002) Progesterone receptor as an indicator of sperm function. Biol Reprod 67:1327–1336

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Fukami K, Yoshida M, Inoue T, Kurokawa M, Fissore RA, Yoshida N, Mikoshiba K, Takenawa T (2003) Phospholipase Cδ4 is required for Ca2+ mobilization essential for acrosome reaction in sperm. J Cell Biol 161:79–88

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Harrison DA, Carr DW, Meizel S (2000) Involvement of protein kinase A and A kinase anchoring protein in the progesterone-initiated human sperm acrosome reaction. Biol Reprod 62:811–820

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Fujinoki M (2013) Progesterone-enhanced sperm hyperactivation through IP3-PKC and PKA signals. Reprod Med Biol 12:27–33

    CAS  Article  Google Scholar 

  50. 50.

    Ignotz GG, Suarez SS (2005) Calcium/calmodulin and calmodulin kinase II stimulate hyperactivation in demembranated bovine sperm. Biol Reprod 73:519–526

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Fujinoki M (2014) Regulation and disruption of hamster sperm hyperactivation by progesterone, 17β-estradiol and diethylstilbestrol. Reprod Med Biol 13:143–152

    CAS  Article  Google Scholar 

  52. 52.

    Iguchi T, Watanabe H, Katsu Y, Mizutani T, Miyagawa S, Suzuki A, Kohno S, Sone K, Kato H (2002) Developmental toxicity of estrogenic chemicals on rodents and other species. Congenit Anom 42:94–105

    CAS  Article  Google Scholar 

  53. 53.

    Iguchi T, Watanabe H, Ohta Y, Blumberg B (2008) Developmental effects: oestrogen-induced vaginal changes and organotin-induced adipogenesis. Intern J Androl 31:263–268

    CAS  Article  Google Scholar 

  54. 54.

    Casao A, Mendoza N, Pérez-Pé R, Grasa P, Abecia J-A, Forcada F, Cebrián-Pérez JA, Muino-Blanco T (2010) Melatonin prevents capacitation and apoptotic-like changes of ram spermatozoa and increases fertility rate. J Pineal Res 48:39–46

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Espino J, Bejarano I, Ortiz A, Lozano GM, García JF, Pariente JA, Rodríguez AB (2010) Melatonin as a potential tool against oxidative damage and apoptosis in ejaculated human spermatozoa. Fertil Steril 94:1915–1917

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Ortiz A, Espino J, Bejarano I, Lozano GM, Mollor F, García JF, Pariente JA, Rodríguez AB (2011) High endogenous melatonin concentrations enhance sperm quality and short-term in vitro exposure to melatonin improves aspects of sperm motility. J Pineal Res 50:132–139

    CAS  PubMed  Google Scholar 

  57. 57.

    Succu S, Berlinguer F, Pasciu V, Satta V, Leoni GG, Naitana S (2011) Melatonin protects ram spermatozoa from cryopreservation injuries in a dose-dependent manner. J Pineal Res 50:310–318

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    O’Flaherty C, de Lamirande E, Gagnon C (2006) Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free Rad Biol Med 41:528–540

    Article  PubMed  Google Scholar 

  59. 59.

    Agarwal A, Makker K, Sharma R (2008) Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immun 59:2–11

    CAS  Article  Google Scholar 

  60. 60.

    de Lamirande E, O’Flaherty C (2008) Sperm activation: role of reactive oxygen species and kinases. Biochim Biophys Acta 1784:106–115

    Article  PubMed  Google Scholar 

  61. 61.

    Iwasaki A, Gagnon C (1992) Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril 57:409–416

    CAS  PubMed  Google Scholar 

  62. 62.

    Bronson FH, Heideman PD (1994) Seasonal regulation of reproduction in mammals. In: Knobil E, Neill JD (eds) The physiology of reproduction, vol 2, 2nd edn. Raven Press, New York

    Google Scholar 

  63. 63.

    Turek FW, Van Cauter E (1994) Rhythms in reproduction. In: Knobil E, Neill JD (eds) The physiology of reproduction, vol 2, 2nd edn. Raven Press, New York

    Google Scholar 

  64. 64.

    Noda M, Higashida H, Aoki S, Wada K (2004) Multiple signal transduction pathways mediated by 5-HT receptors. Mol Neurobiol 29:31–39

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Ganong WF (2005) Reviews of medical physiology, 22nd edn. McGraw-Hill, New York

    Google Scholar 

  66. 66.

    Hu JH, He XB, Wu Q, Yan YC, Koide SS (2002) Biphasic effect of GABA on rat sperm acrosome reaction: involvement of GABAA and GABAB receptors. Arch Androl 48:369–378

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    He X, Zhang Y, Yan Y, Li Y, Koide SS (2003) Identification of GABABR2 in rat testis and sperm. J Reprod Dev 49:397–402

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Kanbara K, Okamoto K, Nomura S, Kaneko T, Shigemoto R, Azuma H, Katsuoka Y, Watanabe M (2005) Cellular localization of GABA and GABAB receptor subunit proteins during spermatogenesis in rat testis. J Androl 26:485–493

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    del Rio RM (1981) Gamma-aminobutyric acid system in rat oviduct. J Biol Chem 256:9816–9819

    Google Scholar 

  70. 70.

    Louzan P, Gallardo MGP, Tramezzani JH (1986) Gamma-aminobutyric acid in the genital tract of the rat during the oestrous cycle. J Reprod Fertil 77:499–524

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Masakatsu Fujinoki.

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The authors declare that they have no conflict of interest that could be perceived as prejudicing the impartiality of the presented research.

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This research did not receive any grants from any funding agencies in the public, commercial, or not-for-profit sectors.

Statement on human rights and the welfare of animals

The experiment was approved by the Animal Care and Use Committee of the Dokkyo Medical University (Experimental permission number: 0107), and carried out according to the Guidelines for Animal Experimentation in the university.

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Fujinoki, M., Takei, G.L. & Kon, H. Non-genomic regulation and disruption of spermatozoal in vitro hyperactivation by oviductal hormones. J Physiol Sci 66, 207–212 (2016). https://doi.org/10.1007/s12576-015-0419-y

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Keywords

  • Amine
  • Amino acid
  • Hyperactivation
  • Non-genomic regulation
  • Spermatozoa
  • Steroid