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Fhl5/Act, a CREM-binding transcriptional activator required for normal sperm maturation and morphology, is not essential for testicular gene expression.

ABSTRACT: BACKGROUND: The LIM domain protein Fhl5 was previously found to interact with CREM, a DNA binding transcriptional regulator necessary for spermiogenesis in mammals. Co-transfection experiments using heterologous promoter constructs indicated a role for Fhl5 in transcriptional up-regulation of CREM-dependent testicular genes. Male mice lacking Fhl5 were reported to be fertile but displayed partially abnormal sperm maturation and morphology. METHODS: To identify Fhl5 testicular target genes we carried out two whole-genome expression profiling experiments using high-density oligonucleotide microarrays and total testis samples from Fhl5 wild-type versus homozygous mutant mice first in different and then in isogenic strain backgrounds. RESULTS: Weak signal differences were detected in non-isogenic samples but no statistically significant expression changes were observed when isogenic Fhl5 mutant and wild-type samples were compared. CONCLUSION: The outcome of these experiments suggests that testicular expression profiling is extremely sensitive to the genetic background and that Fhl5 is not essential for testicular gene expression to a level detected by microarray-based measurements. This might be due to redundant function of the related and similarly expressed protein Fhl4.

SUBMITTER: Lardenois A

PROVIDER: S-EPMC2788571 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Fhl5/Act, a CREM-binding transcriptional activator required for normal sperm maturation and morphology, is not essential for testicular gene expression.

Lardenois Aurélie A Chalmel Frédéric F Demougin Philippe P Kotaja Noora N Sassone-Corsi Paolo P Primig Michael M

Reproductive biology and endocrinology : RB&E 20091124

<h4>Background</h4>The LIM domain protein Fhl5 was previously found to interact with CREM, a DNA binding transcriptional regulator necessary for spermiogenesis in mammals. Co-transfection experiments using heterologous promoter constructs indicated a role for Fhl5 in transcriptional up-regulation of CREM-dependent testicular genes. Male mice lacking Fhl5 were reported to be fertile but displayed partially abnormal sperm maturation and morphology.<h4>Methods</h4>To identify Fhl5 testicular target ...[more]

PMID: 19930692

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Project description:The functional maturation of spermatozoa that is necessary to achieve fertilization occurs as these cells transit through the epididymis, a highly specialized region of the male reproductive tract. A defining feature of this maturation process is that it occurs in the complete absence of nuclear gene transcription or de novo, protein translation in the spermatozoa. Rather, it is driven by sequential interactions between spermatozoa and the complex external milieu in which they are bathed within lumen of the epididymal tubule. A feature of this dynamic microenvironment are epididymosomes, small membrane encapsulated vesicles that are secreted from the epididymal soma. Herein, we report comparative proteomic profiling of epididymosomes isolated from different segments of the mouse epididymis using multiplexed tandem mass tag (TMT) based quantification coupled with high resolution LC-MS/MS. A total of 1640 epididymosome proteins were identified and quantified via this proteomic method. Notably, this analysis revealed pronounced segment-to-segment variation in the encapsulated epididymosome proteome. Thus, 146 proteins were identified as being differentially accumulated between caput and corpus epididymosomes, and a further 344 were differentially accumulated between corpus and cauda epididymosomes (i.e., fold change of ≤ -1.5 or ≥ 1.5; p, < 0.05). Application of gene ontology annotation revealed a substantial portion of the epididymosome proteins mapped to the cellular component of extracellular exosome and to the biological processes of transport, oxidation-reduction, and metabolism. Additional annotation of the subset of epididymosome proteins that have not previously been identified in exosomes revealed enrichment of categories associated with the acquisition of sperm function (e.g., fertilization and binding to the zona pellucida). In tandem with our demonstration that epididymosomes are able to convey protein cargo to the head of maturing spermatozoa, these data emphasize the fundamental importance of epididymosomes as key elements of the epididymal microenvironment responsible for coordinating post-testicular sperm maturation.

Project description:In mammals, sperm cells produced within the testis are structurally differentiated but remain immotile and are unable to fertilize the oocyte unless they undergo a series of maturation events during their transit in the male and female genital tracts. This post-testicular functional maturation is known to rely on the micro-environment of both male and female genital tracts, and is tightly controlled by the pH of their luminal milieus. In particular, within the epididymis, the establishment of a low bicarbonate (HCO3 -) concentration contributes to luminal acidification, which is necessary for sperm maturation and subsequent storage in a quiescent state. Following ejaculation, sperm is exposed to the basic pH of the female genital tract and bicarbonate (HCO3 -), calcium (Ca2+), and chloride (Cl-) influxes induce biochemical and electrophysiological changes to the sperm cells (cytoplasmic alkalinization, increased cAMP concentration, and protein phosphorylation cascades), which are indispensable for the acquisition of fertilization potential, a process called capacitation. Solute carrier 26 (SLC26) members are conserved membranous proteins that mediate the transport of various anions across the plasma membrane of epithelial cells and constitute important regulators of pH and HCO3 - concentration. Most SLC26 members were shown to physically interact and cooperate with the cystic fibrosis transmembrane conductance regulator channel (CFTR) in various epithelia, mainly by stimulating its Cl- channel activity. Among SLC26 members, the function of SLC26A3, A6, and A8 were particularly investigated in the male genital tract and the sperm cells. In this review, we will focus on SLC26s contributions to ionic- and pH-dependent processes during sperm post-testicular maturation. We will specify the current knowledge regarding their functions, based on data from the literature generated by means of in vitro and in vivo studies in knock-out mouse models together with genetic studies of infertile patients. We will also discuss the limits of those studies, the current research gaps and identify some key points for potential developments in this field.

Dataset Information

Fhl5/Act, a CREM-binding transcriptional activator required for normal sperm maturation and morphology, is not essential for testicular gene expression.

Publications

Fhl5/Act, a CREM-binding transcriptional activator required for normal sperm maturation and morphology, is not essential for testicular gene expression.

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