Légaré, C; Akintayo, A; Blondin, P; Calvo, E; Sullivan, R
STUDY QUESTION: Can region-specific transcriptional profiling of the epididymis from fertile and sub-fertile bulls predict the etiology of fertility/sub-fertility in males?
SUMMARY ANSWER: The highly regulated gene expression along the bovine epididymis is affected by the fertility status of bulls used for artificial insemination.
WHAT IS KNOWN ALREADY: In mammals, sperm maturation and storage occur in the epididymis. Each epididymal segment has his own transcriptomic signature that modulates the intraluminal composition and consequently governs sequential modifications of the maturing male gamete.
STUDY DESIGN, SIZE, DURATION: Epididymides from six Holstein bulls with documented fertility were used. These bulls were divided into two groups: high fertility (n = 3), and medium-low fertility (n = 3) and their epididymal transcriptomic profiles were analyzed.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Bovine cDNA microarray probing and bioinformatic tools were used to identify genes that are differentially expressed in caput, corpus and cauda epididymidal tissues of bulls with the documented fertility index.
MAIN RESULTS AND THE ROLE OF CHANCE: Hierarchical clustering and principal component analysis revealed a clear separation between caput, corpus and cauda epididymides. Some transcripts characterize a particular anatomical segment, whereas others are expressed in two out of three epididymal segments. Gene ontology analysis allowed deduction of specific functions played by each epididymal segment. The transcriptional profiles between fertile versus sub-fertile conditions clustered most closely in the corpus and cauda segments, whereas the profiles in the caput segment were distinct between fertile and sub-fertile bulls. Of the differently expressed genes, 10 (AKAP4, SMCP, SPATA3, TCP11, ODF1, CTCFL, SPATA18, ADAM28, SORD and FAM161A) were found to exert functions related to reproductive systems and 5 genes (DEAD, CYST11, DEFB119, DEFB124 and MX1) were found to be associated with the defense response.
LARGE SCALE DATA: The GEO number for public access of bovine epididymis microarray data is GSE96602.
LIMITATIONS, REASONS FOR CAUTION: Further work is required to link these modulations of epididymal functions with sperm fertilizing ability in order to understand the etiology of certain cases of idiopathic infertility in livestock and men.
WIDER IMPLICATIONS OF THE FINDINGS: As fertility can be quantified in bulls used for artificial insemination, this species is a unique model to aid in the understanding of male fertility/sub-fertility in man. Our data provide a molecular characterization that will facilitate advances in understanding the involvement of epididymal physiology in sub/infertility etiology.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant to R.S. from the Natural Sciences and Engineering Research Council (NSERC) of Canada. C.L., A.A., E.C. and R.S. have no conflict of interest to declare. P.B. is R&D director at Alliance Boviteq Inc., a bovine artificial insemination company.
Differential gene expression; Epididymis; Infertility; Male fertility; Microarray analysis; Sperm maturation; Transcriptional network; DEAD box protein; messenger RNA; transcriptome; basic helix loop helix leucine zipper transcription factor; transcriptome; ADAM28 gene; AKAP4 gene; animal tissue; Article; bioinformatics; controlled study; CTCFL gene; CYST11 gene; DEAD gene; DEFB119 gene; DEFB124 gene; down regulation; epididymis; epididymis body; epididymis head; epididymis tail; FAM161A gene; gene; gene expression profiling; gene expression regulation; gene identification; gene ontology; Holstein cattle; male; male fertility; microarray analysis; MX1 gene; nonhuman; ODF1 gene; priority journal; SMCP gene; SORD gene; SPATA18 gene; SPATA3 gene; TCP11 gene; upregulation; animal; artificial insemination; bovine; cytology; DNA microarray; epididymis; fertility; fertilization; gene expression profiling; genetics; growth, development and aging; male infertility; metabolism; pathology; principal component analysis; spermatozoon; spermatozoon maturation; veterinary; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cattle; Epididymis; Fertility; Fertilization; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Infertility, Male; Insemination, Artificial; Male; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; Sperm Maturation; Spermatozoa; Transcriptome