Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2016

Open Access 01-12-2016 | Research

17β-estradiol modifies human spermatozoa mitochondrial function in vitro

Authors: Malgorzata Kotwicka, Izabela Skibinska, Magdalena Jendraszak, Piotr Jedrzejczak

Published in: Reproductive Biology and Endocrinology | Issue 1/2016

Login to get access

Abstract

Background

It is assumed that spermatozoa are target cells for estrogens however, the mechanism of their action is not fully understood. The aim of this study was to investigate the influence of 17β-estradiol (E2) on the human spermatozoa mitochondrial function.

Methods

The effects on spermatozoa of E2 at final concentrations of 10−10, 10−8 and 10−6 M were studied regarding the following phenomena: (1) kinetics of intracellular free calcium ions changes (using Fluo-3), (2) mitochondrial membrane potential ΔΨm (using JC-1 fluorochrome), (3) production of superoxide anion in mitochondria (using MitoSOX RED dye), (4) spermatozoa vitality (propidium iodide staining) and (5) phosphatidylserine membrane translocation (staining with annexin V marked with fluorescein).

Results

E2 initiated rapid (within a few seconds) dose dependent increase of intracellular free calcium ions concentration. E2 was changing the mitochondrial membrane potential: 10−8 M initiated significant increase of percentage of high ΔΨm spermatozoa while the 10−6 M induced significant decrease of high ΔΨm cells. In spermatozoa stimulated with E2 10−6 M a significant increase of mitochondrial superoxide anion level was observed. 2 h incubation of spermatozoa with E2 did not alter cells vitality nor stimulated phosphatidylserine membrane translocation, for all three doses.

Conclusions

17β-estradiol affected the human spermatozoa mitochondrial function. E2 in low concentration improved while in high concentration might deteriorate mitochondrial function.
Literature
1.
go back to reference Carreau S, Bouraima-Lelong H, Delalande C. Estrogens: new players in spermatogenesis. Reprod Biol Society for Biology of Reproduction. 2011;11:174–93. Carreau S, Bouraima-Lelong H, Delalande C. Estrogens: new players in spermatogenesis. Reprod Biol Society for Biology of Reproduction. 2011;11:174–93.
2.
go back to reference Vincenzo R, Bruno M, Cesare C, Chiara D, Lucia Z, Daniele S. Estrogens and male reproduction. South Dartmouth: Endotext. MDText.com, Inc; 2013. Vincenzo R, Bruno M, Cesare C, Chiara D, Lucia Z, Daniele S. Estrogens and male reproduction. South Dartmouth: Endotext. MDText.com, Inc; 2013.
4.
go back to reference Adeoya-Osiguwa S, Markoulaki S, Pocock V, Milligan SR, Fraser LR. 17beta-Estradiol and environmental estrogens significantly affect mammalian sperm function. Hum Reprod. 2003;18:100–7.CrossRefPubMed Adeoya-Osiguwa S, Markoulaki S, Pocock V, Milligan SR, Fraser LR. 17beta-Estradiol and environmental estrogens significantly affect mammalian sperm function. Hum Reprod. 2003;18:100–7.CrossRefPubMed
5.
go back to reference Ded L, Dostalova P, Dorosh A, Dvorakova-Hortova K, Peknicova J. Effect of estrogens on boar sperm capacitation in vitro. Reprod Biol Endocrinol. 2010;8:87.CrossRefPubMedPubMedCentral Ded L, Dostalova P, Dorosh A, Dvorakova-Hortova K, Peknicova J. Effect of estrogens on boar sperm capacitation in vitro. Reprod Biol Endocrinol. 2010;8:87.CrossRefPubMedPubMedCentral
6.
go back to reference Filannino A, Stout TA, Gadella BM, Sostaric E, Pizzi F, Colenbrander B, et al. Dose–response effects of estrogenic mycotoxins (zearalenone, alpha-and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm. Reprod Biol Endocrinol BioMed Central Ltd. 2011;9:134.CrossRef Filannino A, Stout TA, Gadella BM, Sostaric E, Pizzi F, Colenbrander B, et al. Dose–response effects of estrogenic mycotoxins (zearalenone, alpha-and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm. Reprod Biol Endocrinol BioMed Central Ltd. 2011;9:134.CrossRef
7.
go back to reference Guido C, Perrotta I, Panza S, Middea E, Avena P, Santoro M, et al. Human sperm physiology: Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) influence sperm metabolism and may be involved in the pathophysiology of varicocele-associated male infertility. J Cell Physiol. 2011;226:3403–12.CrossRefPubMed Guido C, Perrotta I, Panza S, Middea E, Avena P, Santoro M, et al. Human sperm physiology: Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) influence sperm metabolism and may be involved in the pathophysiology of varicocele-associated male infertility. J Cell Physiol. 2011;226:3403–12.CrossRefPubMed
8.
go back to reference Losel RM, Falkenstein E, Feuring M, Schultz A, Tillmann H-C, Rossol-Haseroth K, et al. Nongenomic steroid action: controversies, questions, and answers. Physiol Rev. 2003;83:965–1016.CrossRefPubMed Losel RM, Falkenstein E, Feuring M, Schultz A, Tillmann H-C, Rossol-Haseroth K, et al. Nongenomic steroid action: controversies, questions, and answers. Physiol Rev. 2003;83:965–1016.CrossRefPubMed
9.
go back to reference Wehling M, Lösel R. Non-genomic steroid hormone effects: Membrane or intracellular receptors? J Steroid Biochem Mol Biol. 2006;102:180–3.CrossRefPubMed Wehling M, Lösel R. Non-genomic steroid hormone effects: Membrane or intracellular receptors? J Steroid Biochem Mol Biol. 2006;102:180–3.CrossRefPubMed
11.
go back to reference Boonyaratanakornkit V. Scaffolding proteins mediating membrane-initiated extra-nuclear actions of estrogen receptor. Steroids Elsevier Inc. 2011;76:877–84. Boonyaratanakornkit V. Scaffolding proteins mediating membrane-initiated extra-nuclear actions of estrogen receptor. Steroids Elsevier Inc. 2011;76:877–84.
12.
go back to reference Levin ER. Minireview: Extranuclear steroid receptors: roles in modulation of cell functions. Mol Endocrinol. 2011;25:377–84.CrossRefPubMed Levin ER. Minireview: Extranuclear steroid receptors: roles in modulation of cell functions. Mol Endocrinol. 2011;25:377–84.CrossRefPubMed
13.
go back to reference Kim HP, Lee JY, Jeong JK, Bae SW, Lee HK, Jo I. Nongenomic stimulation of nitric oxide release by estrogen is mediated by estrogen receptor alpha localized in caveolae. Biochem Biophys Res Commun. 1999;263:257–62.CrossRefPubMed Kim HP, Lee JY, Jeong JK, Bae SW, Lee HK, Jo I. Nongenomic stimulation of nitric oxide release by estrogen is mediated by estrogen receptor alpha localized in caveolae. Biochem Biophys Res Commun. 1999;263:257–62.CrossRefPubMed
14.
go back to reference Rago V, Giordano F, Brunelli E, Zito D, Aquila S, Carpino A. Identification of G protein-coupled estrogen receptor in human and pig spermatozoa. J Anat. 2014;224:732–6.CrossRefPubMedPubMedCentral Rago V, Giordano F, Brunelli E, Zito D, Aquila S, Carpino A. Identification of G protein-coupled estrogen receptor in human and pig spermatozoa. J Anat. 2014;224:732–6.CrossRefPubMedPubMedCentral
15.
go back to reference Arkoun B, Gautier C, Delalande C, Barrier-Battut I, Guenon I, Goux D, et al. Stallion spermatozoa: Putative target of estrogens; presence of the estrogen receptors ESR1, ESR2 and identification of the estrogen-membrane receptor GPER. Gen Comp Endocrinol Elsevier Inc. 2014;200:35–43.CrossRef Arkoun B, Gautier C, Delalande C, Barrier-Battut I, Guenon I, Goux D, et al. Stallion spermatozoa: Putative target of estrogens; presence of the estrogen receptors ESR1, ESR2 and identification of the estrogen-membrane receptor GPER. Gen Comp Endocrinol Elsevier Inc. 2014;200:35–43.CrossRef
16.
go back to reference Aquila S, Sisci D, Gentile M, Middea E, Catalano S, Carpino A, et al. Estrogen receptor (ER)α and ERβ are both expressed in human ejaculated spermatozoa: Evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway. J Clin Endocrinol Metab. 2004;89:1443–51.CrossRefPubMed Aquila S, Sisci D, Gentile M, Middea E, Catalano S, Carpino A, et al. Estrogen receptor (ER)α and ERβ are both expressed in human ejaculated spermatozoa: Evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway. J Clin Endocrinol Metab. 2004;89:1443–51.CrossRefPubMed
17.
go back to reference Solakidi S, Psarra A-MG, Nikolaropoulos S, Sekeris CE. Estrogen receptors alpha and beta (ERalpha and ERbeta) and androgen receptor (AR) in human sperm: localization of ERbeta and AR in mitochondria of the midpiece. Hum Reprod. 2005;20:3481–7.CrossRefPubMed Solakidi S, Psarra A-MG, Nikolaropoulos S, Sekeris CE. Estrogen receptors alpha and beta (ERalpha and ERbeta) and androgen receptor (AR) in human sperm: localization of ERbeta and AR in mitochondria of the midpiece. Hum Reprod. 2005;20:3481–7.CrossRefPubMed
18.
go back to reference Gavrilova-Jordan LP, Price TM. Actions of steroids in mitochondria. Semin Reprod Med. 2007;25:154–64.CrossRefPubMed Gavrilova-Jordan LP, Price TM. Actions of steroids in mitochondria. Semin Reprod Med. 2007;25:154–64.CrossRefPubMed
19.
go back to reference Tavares RS, Martins FC, Oliveira PJ, Ramalho-Santos J, Peixoto FP. Parabens in male infertility-Is there a mitochondrial connection? Reprod Toxicol. 2009;27:1–7.CrossRefPubMed Tavares RS, Martins FC, Oliveira PJ, Ramalho-Santos J, Peixoto FP. Parabens in male infertility-Is there a mitochondrial connection? Reprod Toxicol. 2009;27:1–7.CrossRefPubMed
20.
go back to reference Rajender S, Rahul P, Mahdi AA. Mitochondria, spermatogenesis and male infertility. Mitochondrion. 2010;10:419–28.CrossRefPubMed Rajender S, Rahul P, Mahdi AA. Mitochondria, spermatogenesis and male infertility. Mitochondrion. 2010;10:419–28.CrossRefPubMed
22.
go back to reference Chen JQ, Eshete M, Alworth WL, Yager JD. Binding of MCF-7 cell mitochondrial proteins and recombinant human estrogen receptors alpha and beta to human mitochondrial DNA estrogen response elements. J Cell Biochem. 2004;93:358–73.CrossRefPubMed Chen JQ, Eshete M, Alworth WL, Yager JD. Binding of MCF-7 cell mitochondrial proteins and recombinant human estrogen receptors alpha and beta to human mitochondrial DNA estrogen response elements. J Cell Biochem. 2004;93:358–73.CrossRefPubMed
23.
go back to reference Psarra AMG, Sekeris CE. Nuclear receptors and other nuclear transcription factors in mitochondria: Regulatory molecules in a new environment. Biochim Biophys Acta-Mol Cell Res. 2008;1783:1–11.CrossRef Psarra AMG, Sekeris CE. Nuclear receptors and other nuclear transcription factors in mitochondria: Regulatory molecules in a new environment. Biochim Biophys Acta-Mol Cell Res. 2008;1783:1–11.CrossRef
24.
go back to reference Chen JQ, Delannoy M, Cooke C, Yager JD. Mitochondrial localization of ERalpha and ERbeta in human MCF7 cells. Am J Physiol Endocrinol Metab. 2004;286:E1011–22.CrossRefPubMed Chen JQ, Delannoy M, Cooke C, Yager JD. Mitochondrial localization of ERalpha and ERbeta in human MCF7 cells. Am J Physiol Endocrinol Metab. 2004;286:E1011–22.CrossRefPubMed
25.
go back to reference Breitbart H, Rubinstein S, Gruberger M. Calcium efflux mechanism in sperm mitochondria. Biochim. Biophys. Acta-Mol. Cell Res. 1996;1312:79–84. Breitbart H, Rubinstein S, Gruberger M. Calcium efflux mechanism in sperm mitochondria. Biochim. Biophys. Acta-Mol. Cell Res. 1996;1312:79–84.
26.
go back to reference Tatoyan A, Giulivi C. Purification and characterization of a nitric-oxide synthase from rat liver mitochondria. J Biol Chem. 1998;273:11044–8.CrossRefPubMed Tatoyan A, Giulivi C. Purification and characterization of a nitric-oxide synthase from rat liver mitochondria. J Biol Chem. 1998;273:11044–8.CrossRefPubMed
27.
go back to reference Koppers AJ, De Iuliis GN, Finnie JM, McLaughlin EA, Aitken RJ. Significance of Mitochondrial Reactive Oxygen Species in the Generation of Oxidative Stress in Spermatozoa. J Clin Endocrinol Metab. 2008;93:3199–207.CrossRefPubMed Koppers AJ, De Iuliis GN, Finnie JM, McLaughlin EA, Aitken RJ. Significance of Mitochondrial Reactive Oxygen Species in the Generation of Oxidative Stress in Spermatozoa. J Clin Endocrinol Metab. 2008;93:3199–207.CrossRefPubMed
28.
go back to reference Paoli D, Gallo M, Rizzo F, Baldi E, Francavilla S, Lenzi A, et al. Mitochondrial membrane potential profile and its correlation with increasing sperm motility. Fertil Steril. 2011;95:2315–9.CrossRefPubMed Paoli D, Gallo M, Rizzo F, Baldi E, Francavilla S, Lenzi A, et al. Mitochondrial membrane potential profile and its correlation with increasing sperm motility. Fertil Steril. 2011;95:2315–9.CrossRefPubMed
29.
go back to reference Marchetti P, Ballot C, Jouy N, Thomas P, Marchetti C. Influence of mitochondrial membrane potential of spermatozoa on in vitro fertilisation outcome. Andrologia. 2012;44:136–41.CrossRefPubMed Marchetti P, Ballot C, Jouy N, Thomas P, Marchetti C. Influence of mitochondrial membrane potential of spermatozoa on in vitro fertilisation outcome. Andrologia. 2012;44:136–41.CrossRefPubMed
30.
go back to reference Paventi G, Lessard C, Bailey JL, Passarella S. In boar sperm capacitation l-lactate and succinate, but not pyruvate and citrate, contribute to the mitochondrial membrane potential increase as monitored via safranine O fluorescence. Biochem Biophys Res Commun. 2015;462:257–62.CrossRefPubMed Paventi G, Lessard C, Bailey JL, Passarella S. In boar sperm capacitation l-lactate and succinate, but not pyruvate and citrate, contribute to the mitochondrial membrane potential increase as monitored via safranine O fluorescence. Biochem Biophys Res Commun. 2015;462:257–62.CrossRefPubMed
31.
go back to reference Horvat A, Nikezić G, Petrović S, Kanazir DT, Nikezie G, Petrovic S, et al. Binding of estradiol to synaptosomal mitochondria: physiological significance. Cell Mol Life Sci. 2001;58:636–44.CrossRefPubMed Horvat A, Nikezić G, Petrović S, Kanazir DT, Nikezie G, Petrovic S, et al. Binding of estradiol to synaptosomal mitochondria: physiological significance. Cell Mol Life Sci. 2001;58:636–44.CrossRefPubMed
32.
go back to reference Petrović S, Demajo M, Horvat A. Estradiol affects calcium transport across mitochondrial membrane in different brain regions. Ann N Y Acad Sci. 2005;1048:341–3.CrossRefPubMed Petrović S, Demajo M, Horvat A. Estradiol affects calcium transport across mitochondrial membrane in different brain regions. Ann N Y Acad Sci. 2005;1048:341–3.CrossRefPubMed
33.
go back to reference Bennetts LE, De Iuliis GN, Nixon B, Kime M, Zelski K, McVicar CM, et al. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities. Mutat Res-Fundam Mol Mech Mutagen. 2008;641:1–11.CrossRef Bennetts LE, De Iuliis GN, Nixon B, Kime M, Zelski K, McVicar CM, et al. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities. Mutat Res-Fundam Mol Mech Mutagen. 2008;641:1–11.CrossRef
34.
go back to reference Mishra DP, Shaha C. Estrogen-induced spermatogenic cell apoptosis occurs via the mitochondrial pathway: role of superoxide and nitric oxide. J Biol Chem. 2005;280:6181–96.CrossRefPubMed Mishra DP, Shaha C. Estrogen-induced spermatogenic cell apoptosis occurs via the mitochondrial pathway: role of superoxide and nitric oxide. J Biol Chem. 2005;280:6181–96.CrossRefPubMed
35.
go back to reference Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26:1628–40.CrossRefPubMed Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26:1628–40.CrossRefPubMed
36.
go back to reference Kim SH, Yu DH, Kim YJ. Apoptosis-like change, ROS, and DNA status in cryopreserved canine sperm recovered by glass wool filtration and Percoll gradient centrifugation techniques. Anim Reprod Sci. 2010;119:106–14.CrossRefPubMed Kim SH, Yu DH, Kim YJ. Apoptosis-like change, ROS, and DNA status in cryopreserved canine sperm recovered by glass wool filtration and Percoll gradient centrifugation techniques. Anim Reprod Sci. 2010;119:106–14.CrossRefPubMed
37.
go back to reference Aitken RJ, Gibb Z, Baker MA, Drevet J, Gharagozloo P. Causes and consequences of oxidative stress in spermatozoa. Reprod Fertil Dev. 2015;28:1–10.CrossRef Aitken RJ, Gibb Z, Baker MA, Drevet J, Gharagozloo P. Causes and consequences of oxidative stress in spermatozoa. Reprod Fertil Dev. 2015;28:1–10.CrossRef
38.
go back to reference Kotwicka M, Filipiak K, Jedrzejczak P, Warchol JB. Caspase-3 activation and phosphatidylserine membrane translocation in human spermatozoa: is there a relationship? Reprod Biomed Online. 2008;16:657–63.CrossRefPubMed Kotwicka M, Filipiak K, Jedrzejczak P, Warchol JB. Caspase-3 activation and phosphatidylserine membrane translocation in human spermatozoa: is there a relationship? Reprod Biomed Online. 2008;16:657–63.CrossRefPubMed
39.
go back to reference Kotwicka M, Jendraszak M, Skibinska I, Jedrzejczak P, Pawelczyk L. Decreased motility of human spermatozoa presenting phosphatidylserine membrane translocation-cells selection with the swim-up technique. Hum Cell. 2013;26:28–34.CrossRefPubMed Kotwicka M, Jendraszak M, Skibinska I, Jedrzejczak P, Pawelczyk L. Decreased motility of human spermatozoa presenting phosphatidylserine membrane translocation-cells selection with the swim-up technique. Hum Cell. 2013;26:28–34.CrossRefPubMed
40.
go back to reference Grunewald S, Baumann T, Paasch U, Glander HJ. Capacitation and acrosome reaction in nonapoptotic human spermatozoa. Ann N Y Acad Sci. 2006;1090:138–46.CrossRefPubMed Grunewald S, Baumann T, Paasch U, Glander HJ. Capacitation and acrosome reaction in nonapoptotic human spermatozoa. Ann N Y Acad Sci. 2006;1090:138–46.CrossRefPubMed
41.
go back to reference Grunewald S, Kriegel C, Baumann T, Glander HJ, Paasch U. Interactions between apoptotic signal transduction and capacitation in human spermatozoa. Hum Reprod. 2009;24:2071–8.CrossRefPubMed Grunewald S, Kriegel C, Baumann T, Glander HJ, Paasch U. Interactions between apoptotic signal transduction and capacitation in human spermatozoa. Hum Reprod. 2009;24:2071–8.CrossRefPubMed
42.
go back to reference Psarra AMG, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of steroid and thyroid hormones: Presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol Cell Endocrinol. 2006;246:21–33.CrossRefPubMed Psarra AMG, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of steroid and thyroid hormones: Presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol Cell Endocrinol. 2006;246:21–33.CrossRefPubMed
43.
go back to reference Lu A, Frink M, Choudhry M, Schwacha MG, Hubbard WJ, Rue LW, et al. Mitochondria play an important role in 17beta-estradiol attenuation of H (2) O (2)-induced rat endothelial cell apoptosis. Am J Physiol Endocrinol Metab. 2007;292:E585–93.CrossRefPubMed Lu A, Frink M, Choudhry M, Schwacha MG, Hubbard WJ, Rue LW, et al. Mitochondria play an important role in 17beta-estradiol attenuation of H (2) O (2)-induced rat endothelial cell apoptosis. Am J Physiol Endocrinol Metab. 2007;292:E585–93.CrossRefPubMed
44.
go back to reference Wang J, Green PS, Simpkins JW. Estradiol protects against ATP depletion, mitochondrial membrane potential decline and the generation of reactive oxygen species induced by 3-nitroproprionic acid in SK-N-SH human neuroblastoma cells. J Neurochem. 2001;77:804–11.CrossRefPubMed Wang J, Green PS, Simpkins JW. Estradiol protects against ATP depletion, mitochondrial membrane potential decline and the generation of reactive oxygen species induced by 3-nitroproprionic acid in SK-N-SH human neuroblastoma cells. J Neurochem. 2001;77:804–11.CrossRefPubMed
Metadata
Title
17β-estradiol modifies human spermatozoa mitochondrial function in vitro
Authors
Malgorzata Kotwicka
Izabela Skibinska
Magdalena Jendraszak
Piotr Jedrzejczak
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2016
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-016-0186-5

Other articles of this Issue 1/2016

Reproductive Biology and Endocrinology 1/2016 Go to the issue