Role of Angiotensin-(1–7) via MAS receptor in human sperm motility and acrosome reaction

Rennin-angiotensin system (RAS) has been involved in sperm function, even so, little is known about the implication of one of the RAS axis formed by Ang-(1–7) (angiotensin-(1–7)) and MAS receptor. Hence, in the present work, we focused on elucidating the function of the MAS receptor in human spermatozoa. We analyzed the expression and localization of MAS receptor in human spermatozoa and we observed if its activation is able to modulate the sperm motility of normal motility and/or asthenozoospermic patients, as well as, the acrosome reaction of the spermatozoa. MAS receptor is present in human mature spermatozoa, not only at the mRNA level but also at protein level. MAS is localized at the acrosome region, as well as, in the tail of spermatozoa. The sperm incubation with MAS agonist Ang-(1–7) activates at dose-dependent manner the PI3K/AKT pathway (P < 0.01 vs control) and improves the motility of asthenozoospermic patients (P < 0.01 vs control), which is blocked by the specific antagonist (A779) (P < 0.01), but it do not modulate the acrosome reaction. These findings suggest that the ACE2/Ang-(1–7)/Mas axis may be a useful biochemical tool for the treatment of male infertility related to sperm mobility.

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PACAP-mediated sperm–cumulus cell interaction promotes fertilization

Reproduction ◽

10.1530/rep-10-0201 ◽

2011 ◽

Vol 141 (2) ◽

pp. 163-171 ◽

Cited By ~ 30

Author(s):

Ichiro Tanii ◽

Tadashi Aradate ◽

Kouhei Matsuda ◽

Akira Komiya ◽

Hideki Fuse

Keyword(s):

Sperm Motility ◽

Acrosome Reaction ◽

Cumulus Cell ◽

Cumulus Cells ◽

Cell Interaction ◽

Fertilization Rate ◽

Type I ◽

Dependent Manner ◽

Sperm Penetration

The developing acrosome in spermatids contains pituitary adenylate cyclase-activating polypeptide (PACAP). However, the role of the acrosomal PACAP remains unclear because it has not been detected in mature spermatids and sperm. We reinvestigated whether the sperm acrosome contains PACAP. An antiserum produced against PACAP reacted to the anterior acrosome in epididymal sperm fixed under mild conditions, suggesting that PACAP acts on oocytes and/or cumulus cells at the site of fertilization. Immunolabeling and RT-PCR demonstrated the presence of PACAP type I receptor, a PACAP-specific receptor, in postovulatory cumulus cells. To investigate the role of PACAP in fertilization, we pretreated cumulus–oocyte complexes with the polypeptide. At a low concentration of sperm, the fertilization rate was significantly enhanced by PACAP in a dose-dependent manner. Sperm penetration through the oocyte investment, cumulus layer, and zona pellucida was also enhanced by PACAP. The enhancement was probably due to an enhancement in sperm motility and the zona-induced acrosome reaction, which were stimulated by a cumulus cell-releasing factor. Indeed, PACAP treatment increased the secretion of progesterone from the cumulus–oocyte complexes. These results strongly suggest that in response to PACAP, cumulus cells release a soluble factor that probably stimulates sperm motility and the acrosome reaction, thereby promoting fertilization.

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Low physiological levels of prostaglandins E2 and F2α improve human sperm functions

Reproduction Fertility and Development ◽

10.1071/rd14035 ◽

2016 ◽

Vol 28 (4) ◽

pp. 434 ◽

Cited By ~ 4

Author(s):

Mariana Rios ◽

Daniela V. Carreño ◽

Carolina Oses ◽

Nelson Barrera ◽

Bredford Kerr ◽

...

Keyword(s):

Intracellular Calcium ◽

Sperm Motility ◽

Acrosome Reaction ◽

Seminal Fluid ◽

Human Sperm ◽

Human Spermatozoa ◽

Control Solution ◽

Prostaglandins E2 And F2α ◽

Motility Parameters ◽

Sperm Functions

Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2α concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1 μM PGE2, 1 μM PGF2α or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18 h with PGE2 or PGF2α resulted in a significant (P < 0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2α, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2α increases sperm functions and could improve conditions for assisted reproduction protocols.

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Stimulation of platelet-activating factor synthesis by progesterone and A23187 in human spermatozoa

Biochemical Journal ◽

10.1042/bj2920209 ◽

1993 ◽

Vol 292 (1) ◽

pp. 209-216 ◽

Cited By ~ 37

Author(s):

E Baldi ◽

C Falsetti ◽

C Krausz ◽

G Gervasi ◽

V Carloni ◽

...

Keyword(s):

Acrosome Reaction ◽

Platelet Activating Factor ◽

Human Sperm ◽

Human Spermatozoa ◽

Acetate Incorporation ◽

Acid Release ◽

Similar Kinetic ◽

Mammalian Spermatozoa ◽

Stimulation Of

The presence of platelet-activating factor (PAF) has been demonstrated recently in mammalian spermatozoa, together with evidence for a role of this phospholipid in enhancing sperm motility and fertilizing ability. To investigate whether PAF synthesis and release occurs in human spermatozoa following incubation with stimuli that induce acrosome reaction, spermatozoa were incubated with progesterone and A23187, two known inducers of the exocytotic event. PAF synthesis (remodelling pathway) was assessed by [3H]acetate incorporation into PAF. Treatment of spermatozoa with progesterone and A23187 resulted in an increase of [3H]acetate incorporation into PAF. Most of the newly synthesized [3H]PAF formed in response to acrosome reaction was found in the supernatant, suggesting a release of the phospholipid from spermatozoa. PAF-like material extracted from human spermatozoa was able to induce aggregation of rabbit platelets and showed identical retention time and the same ion m/e values as authentic PAF when analysed with g.c.-m.s. Lyso-PAF:acetyl-CoA acetyltransferase (EC 2.3.1.67) activity in human spermatozoa was also studied and showed similar kinetic parameters to those described for other cell systems. Stimulation of spermatozoa with progesterone and A23187 induced an increase of [3H]arachidonic acid release, suggesting an activation of phospholipase A. In conclusion, our results demonstrated increased production and release of PAF in human sperm following stimulation with progesterone and A23187 and suggest a role for this phospholipid in the activation of spermatozoa.

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Inhibition of sperm - egg binding and fertilisation in mice by a monoclonal antibody reactive to 57-kDa human sperm surface antigen

Reproduction Fertility and Development ◽

10.1071/rd06028 ◽

2006 ◽

Vol 18 (8) ◽

pp. 875 ◽

Cited By ~ 2

Author(s):

K. V. R. Reddy ◽

G. Vijayalaxmi ◽

K. S. Rajeev ◽

C. Aranha

Keyword(s):

Present Report ◽

Mammalian Species ◽

Human Sperm ◽

Equatorial Region ◽

Human Spermatozoa ◽

Dependent Manner ◽

Egg Recognition ◽

Sperm Antigens ◽

Dose Dependent

Monoclonal antibodies (mAbs) against spermatozoa are a popular approach to define sperm antigens involved in the process of fertilisation. The identification and characterisation of a 57-kDa fertility asssociated sperm antigen (FASA-57) from human spermatozoa was reported in an earlier paper by the authors. In the present report, studies to develop mAbs against partially purified FASA-57 are extended. From a panel of mAbs raised, one clone designated as 3H4B9 was selected and characterised because it recognised native FASA-57. Indirect immunofluorescence studies revealed that FASA-57 localised on the acrosome of non-acrosome-reacted human spermatozoa and on the equatorial region after the acrosome reaction. Spermatozoa from several other mammalian species were also found to express this antigen, suggesting its evolutionary conservation across the species. The antigen localised specifically in spermatogonial cells and luminal spermatozoa of the testis and epididymis. Western blot studies showed the presence of a FASA-57-like protein in the mouse brain also, indicating that testis and brain share antigenic similarities. Further, the role of FASA-57 in sperm–egg interaction was investigated using a mouse model. The mAb 3H4B9 inhibited sperm–egg binding and fusion in a dose-dependent manner with half-maximal inhibition at 2 µg mL–1. In conclusion, FASA-57 appears to play an important role in sperm–egg recognition, fusion and fertilisation. Therefore, FASA-57 could be used as a diagnostic marker in the evaluation of male infertility.

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The role of follicular fluid in inducing the acrosome reaction of human spermatozoa incubated in vitro

Human Reproduction ◽

10.1093/oxfordjournals.humrep.a136866 ◽

1989 ◽

Vol 4 (2) ◽

pp. 169-174 ◽

Cited By ~ 34

Author(s):

D. Mortimer ◽

A.R. Camenzind

Keyword(s):

Follicular Fluid ◽

Acrosome Reaction ◽

Human Spermatozoa

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Role of the Serine/Threonine Phosphatases During the Progesterone-Induced Acrosome Reaction and Increase in Intracellular Free Calcium Concentration in Human Sperm.

Biology of Reproduction ◽

10.1093/biolreprod/85.s1.494 ◽

2011 ◽

Vol 85 (Suppl_1) ◽

pp. 494-494

Author(s):

Patricio Morales ◽

Lina Baron ◽

Karla Fara ◽

Emilce S. Diaz ◽

Janetti Signorelli

Keyword(s):

Acrosome Reaction ◽

Calcium Concentration ◽

Human Sperm ◽

Intracellular Free Calcium ◽

Free Calcium ◽

Intracellular Free Calcium Concentration ◽

Free Calcium Concentration

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Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis

Molecules ◽

10.3390/molecules25184231 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4231

Author(s):

Xiatian Li ◽

Tao Luo ◽

Hua Li ◽

Nianlong Yan

Keyword(s):

Signaling Pathways ◽

Sperm Motility ◽

Acrosome Reaction ◽

Caspase 3 ◽

Human Sperm ◽

Erk Signaling ◽

Sperm Function ◽

Sphingomyelin Synthase ◽

Protein Levels ◽

Penetration Ability

Sphingomylin participates in sperm function in animals, and also regulates the Akt and ERK signaling pathways, both of which are associated with the asthenospermia. Sphingomyelin synthase 2 (SMS2) is involved in the biosynthesis of sphingomylin. To determine the relationship between SMS2 and human sperm function, we analyzed the distribution of SMS2 in human sperm and testes, and SMS2 expression in patients with asthenospermia and normozoospermia; human sperm were treated with anti-SMS2, and the sperm motility, penetration ability into methylcellulose, capacitation and acrosome reaction, and sperm [Ca2+]i imaging were evaluated, while the Akt and ERK pathway and cleaved caspase 3 were also analyzed. Results showed that SMS2 was localized in the testis and human sperm, and the protein levels of normozoospermia were higher than asthenospermia. Inhibition of SMS2 activity significantly decreased sperm motility and penetration ability into methylcellulose, but had no influence on capacitation and acrosome reaction, or on intracellular [Ca2+]i compared to IgG-treated control groups. Moreover, the phosphorylation level of Akt was decreased, whereas the phosphorylation of ERK and cleaved-caspase 3 levels were significantly increased. Taken together, SMS2 can affect sperm motility and penetration ability into methylcellulose, and participate in apoptosis associated with the Akt and ERK signaling pathways.

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Lysine glutarylation in human sperm is associated with progressive motility

Human Reproduction ◽

10.1093/humrep/dez068 ◽

2019 ◽

Vol 34 (7) ◽

pp. 1186-1194 ◽

Cited By ~ 3

Author(s):

Yi-min Cheng ◽

Xiao-nian Hu ◽

Zhen Peng ◽

Ting-ting Pan ◽

Fang Wang ◽

...

Keyword(s):

Sperm Motility ◽

Natural Science ◽

Hot Spot ◽

Human Sperm ◽

Mature Sperm ◽

Computer Assisted ◽

Structured Illumination Microscopy ◽

Progressive Motility ◽

Wide Range

AbstractSTUDY QUESTIONIs there a role for lysine glutarylation (Kglu), a newly identified protein post-translational modification (PTM), in human sperm?SUMMARY ANSWERKglu occurs in several proteins located in the tail of human sperm, and it was reduced in asthenozoospermic (A) men and positively correlated with progressive motility of human sperm, indicating its important role in maintaining sperm motility.WHAT IS KNOWN ALREADYSince mature sperm are almost transcriptionally silent, PTM is regarded as an important pathway in regulating sperm function. However, only phosphorylation has been extensively studied in mature sperm to date. Protein lysine modification (PLM), a hot spot of PTMs, was rarely studied except for a few reports on lysine methylation and acetylation. As a newly identified PLM, Kglu has not been well characterized, especially in mature sperm.STUDY DESIGN, SIZE, DURATIONSperm samples were obtained from normozoospermic (N) men and A men who visited the reproductive medical center between February 2016 and January 2018. In total, 61 N men and 59 A men were recruited to participate in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSKglu was examined by immunoblotting and immunofluorescence assays using a previously qualified pan-anti-glutaryllysine antibody that recognizes glutaryllysine in a wide range of sequence contexts (both in histones and non-histone substrates) but not the structurally similar malonyllysine and succinyllysine. The immunofluorescence assay was imaged using laser scanning confocal microscopy and super-resolution structured illumination microscopy. Sperm motility parameters were examined by computer-assisted sperm analysis.MAIN RESULTS AND THE ROLE OF CHANCEKglu occurs in several proteins (20–150 kDa) located in the tail of human sperm, especially in the middle piece and the latter part of the principal piece. Sperm Kglu was modulated by regulatory systems (enzymes and glutaryl-CoA) similar to those in HeLa cells. The mean level of sperm Kglu was significantly reduced in A men compared with N men (P < 0.001) and was positively correlated with progressive motility (P < 0.001). The sodium glutarate-induced elevation of Kglu levels in A men with lower Kglu levels in sperm significantly improved the progressive motility (P < 0.001). Furthermore, the reduced sperm Kglu levels in A men was accompanied by an increase in sperm glutaryl-CoA dehydrogenase (a regulatory enzyme of Kglu).LARGE SCALE DATAN/ALIMITATIONS, REASONS FOR CAUTIONAlthough the present study indicated the involvement of sperm Kglu in maintaining progressive motility of human sperm, the underlying mechanism needs to be investigated further.WIDER IMPLICATIONS OF THE FINDINGSThe findings of this study provide an insight into the novel role of Kglu in human sperm and suggest that abnormality of sperm PLMs may be one of the causes of asthenozoospermia.STUDY FUNDING/COMPETING INTEREST(S)National Natural Science Foundation of China (81 771 644 to T.L.; 31 671 204 to X.Z. and 81 871 207 to H.C.); National Basic Research Program of China (973 Program, 2015CB943003 to X.Z.); Natural Science Foundation of Jiangxi, China (20171ACB21006 and 20161BAB204167 to T.L.; 20165BCB18001 to X.Z.). The authors have no conflicts of interest to declare.

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