Evidence Suggesting Involvement of a Unique Human Sperm Steroid Receptor/Cl- Channel Complex in the Progesterone-Initiated Acrosome Reaction

Aurell, Christina; Meizel, Wistrom Stanley

doi:10.1006/dbio.1993.1274

Cited by 148 publications

(11 citation statements)

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“…GABA and its receptor-mediated signal transduction system is thought to contribute to sperm capacitation. In human sperm, the GABA A receptor was detected in the equatorial region [33], while in this study the GABA A receptor was detected in the acrosomal region of mouse sperm. The expression patterns of the dopamine type 2 receptor (DRD2) reportedly also differ between human and mouse sperm [34], suggesting that interspecies differences in sperm morphology may be responsible for the different receptor expression patterns.…”

Section: Discussionmentioning

confidence: 59%

Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration

et al. 2019

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In mammals, ejaculated sperm acquire their fertilizing ability during migration through the female reproductive tract, which secretes several factors that contribute to sperm capacitation. Gamma-aminobutyric acid (GABA) is a well-known neurotransmitter in the central nervous system, but additionally enhances the sperm acrosome reaction in the rat and cow. However, the detailed effects of GABA concentration on sperm function remain unclear. In this study, we detected the presence of the GABA type A receptor (GABA A) in mouse epididymal sperm by western blot analysis and in the sperm acrosome by immunocytochemistry. We also investigated the effects of GABA on sperm fertilizing ability. We found that GABA facilitated the tyrosine phosphorylation of sperm proteins, which is an index of sperm capacitation. GABA also promoted the acrosome reaction, which was suppressed by a selective GABA A receptor antagonist. We then found that the effective GABA concentration for the acrosome reaction corresponds to sperm concentration, but we did not detect any marked effect of GABA on sperm motility using a computer-assisted sperm analysis system. Using immunohistochemistry, we also detected GABA expression in the epithelia of the mouse uterus and oviduct. Furthermore, we found that the mRNA levels of glutamate decarboxylase ( Gad ), which generates GABA from L-glutamate, were higher in the oviduct than in the uterus, and that Gad mRNA levels were higher at estrus than at the diestrus stage. These results indicate that the GABA concentration can act as a modulator of the acrosome reaction and sperm capacitation in the female reproductive tract.

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Section: Discussionmentioning

confidence: 59%

Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration

et al. 2019

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“…In sperm, the effects of P 4 can be influenced by GABAA receptor antagonist, bicuculline [26][27][28]. Bicuculline also blocked P 4 's anti-mitotic and anti-apoptotic action in GCs (Fig.…”

Section: Resultsmentioning

confidence: 88%

Progesterone Mediates its Anti-Mitogenic and Anti-Apoptotic Actions in Rat Granulosa Cells Through a Progesterone-Binding Protein With Gamma Aminobutyric AcidA Receptor-Like Features1

Peluso

Pappalardo

1998

Biology of Reproduction

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Progesterone (P4) inhibits small granulosa cell (GC) mitosis and large GC apoptosis. These actions are steroid specific and dose dependent and are inhibited by the progesterone receptor (PR) antagonist, RU-486. However, these cells do not express the nuclear PR but rather an ill-defined P4-binding protein (P4BP). This binding protein could function as a receptor and mediate P4's actions in GCs. Therefore, a series of studies was designed to characterize this P4BP. First, an antibody directed against the ligand-binding site of the nuclear PR was used in a Western blot analysis. This analysis revealed the presence of a 60-kDa P4BP within ovarian and GC lysates as well as within an ovarian membrane preparation. This protein was not observed in lysates of cells derived from the ovarian surface epithelium. In addition, this P4BP was immunoprecipitated by an antibody to the alpha1 chain of the gamma aminobutyric acidA (GABA(A)) receptor, suggesting that the P4BP could be the ovarian GABA(A) receptor. Since activation of the rat ovarian GABA(A) receptor increases intracellular cAMP levels, GCs were cultured with control medium supplemented with either 8-bromo-cAMP (8-br-cAMP), P4, or muscimol (a GABA agonist). Increases in cAMP were detected by monitoring the cAMP-dependent phosphorylation of cAMP response element-binding protein (CREB). Phosphorylated CREB was not observed in control or P4-treated cultures, but it was detected in the majority of both small and large GCs exposed to either 8-br-cAMP or muscimol. Since activation of the GABA(A) receptor with muscimol increases phosphorylated CREB but P4 does not, this study indicates that P4 does not activate the ovarian GABA(A) receptor. However, both bicuculline, a GABA(A) receptor antagonist, and the antibody to PR inhibited P4's ability to prevent both insulin-dependent mitosis and apoptosis. Collectively, these studies suggest that P4 mediates its anti-mitotic and anti-apoptotic effects through this 60-kDa P4BP, which has GABA(A) receptor-like properties and is localized within the surface membrane of GCs.

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“…Some nongenomic progesterone receptors have been reported to be present in mammalian sperm membrane, including CatSper (see the references in [ 22 , 23 , 49 ]). Early observations indicated the involvement of a unique human sperm steroid receptor/Cl − channel complex in the progesterone-initiated AR [ 50 ]. In other studies, it was proposed that a gamma-aminobutyric acid-like receptor participates in this process in mouse spermatozoa [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

A Specific Transitory Increase in Intracellular Calcium Induced by Progesterone Promotes Acrosomal Exocytosis in Mouse Sperm1

Romarowski

Sánchez-Cárdenas

Ramírez-Gómez

et al. 2016

Biology of Reproduction

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During capacitation, sperm acquire the ability to undergo the acrosome reaction (AR), an essential step in fertilization. Progesterone produced by cumulus cells has been associated with various physiological processes in sperm, including stimulation of AR. An increase in intracellular Ca2+ ([Ca2+]i) is necessary for AR to occur. In this study, we investigated the spatiotemporal correlation between the changes in [Ca2+]i and AR in single mouse spermatozoa in response to progesterone. We found that progesterone stimulates an [Ca2+]i increase in five different patterns: gradual increase, oscillatory, late transitory, immediate transitory, and sustained. We also observed that the [Ca2+]i increase promoted by progesterone starts at either the flagellum or the head. We validated the use of FM4-64 as an indicator for the occurrence of the AR by simultaneously detecting its fluorescence increase and the loss of EGFP in transgenic EGFPAcr sperm. For the first time, we have simultaneously visualized the rise in [Ca2+]i and the process of exocytosis in response to progesterone and found that only a specific transitory increase in [Ca2+]i originating in the sperm head promotes the initiation of AR.

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Evidence Suggesting Involvement of a Unique Human Sperm Steroid Receptor/Cl- Channel Complex in the Progesterone-Initiated Acrosome Reaction

Cited by 148 publications

References 0 publications

Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration

Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration

Progesterone Mediates its Anti-Mitogenic and Anti-Apoptotic Actions in Rat Granulosa Cells Through a Progesterone-Binding Protein With Gamma Aminobutyric AcidA Receptor-Like Features1

A Specific Transitory Increase in Intracellular Calcium Induced by Progesterone Promotes Acrosomal Exocytosis in Mouse Sperm1

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