What can we learn about fertilization from cystic fibrosis?

Florman, Harvey M.; Jungnickel, Melissa K.; Sutton, Keith A.

doi:10.1073/pnas.0703626104

Cited by 11 publications

(9 citation statements)

References 17 publications

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“…These included cytoskeleton and G-protein coupled receptor activities, transmembrane transport, ion channels, and mitochondrial ribosomal proteins-functions involved in sperm chemotaxis, capacitation, sperm-egg interactions, and the acrosome reaction [62], [63], [64]. For example, ion channels play an important role in fertilization by facilitating interactions of the sperm with its environment and the egg during capacitation, sperm-egg recognition, and the acrosome reaction [65], [66]. Trans-membrane transport of glycoproteins on the surface of sperm tails, on the other hand, is required for primary binding of the sperm to the zona pellucida during capacitation and sperm-cumulus interaction [67].…”

Section: Discussionmentioning

confidence: 99%

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding and Regulatory RNAs as Revealed by Microarray Analysis and RNA-seq

et al. 2013

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Mature mammalian sperm contain a complex population of RNAs some of which might regulate spermatogenesis while others probably play a role in fertilization and early development. Due to this limited knowledge, the biological functions of sperm RNAs remain enigmatic. Here we report the first characterization of the global transcriptome of the sperm of fertile stallions. The findings improved understanding of the biological significance of sperm RNAs which in turn will allow the discovery of sperm-based biomarkers for stallion fertility. The stallion sperm transcriptome was interrogated by analyzing sperm and testes RNA on a 21,000-element equine whole-genome oligoarray and by RNA-seq. Microarray analysis revealed 6,761 transcripts in the sperm, of which 165 were sperm-enriched, and 155 were differentially expressed between the sperm and testes. Next, 70 million raw reads were generated by RNA-seq of which 50% could be aligned with the horse reference genome. A total of 19,257 sequence tags were mapped to all horse chromosomes and the mitochondrial genome. The highest density of mapped transcripts was in gene-rich ECA11, 12 and 13, and the lowest in gene-poor ECA9 and X; 7 gene transcripts originated from ECAY. Structural annotation aligned sperm transcripts with 4,504 known horse and/or human genes, rRNAs and 82 miRNAs, whereas 13,354 sequence tags remained anonymous. The data were aligned with selected equine gene models to identify additional exons and splice variants. Gene Ontology annotations showed that sperm transcripts were associated with molecular processes (chemoattractant-activated signal transduction, ion transport) and cellular components (membranes and vesicles) related to known sperm functions at fertilization, while some messenger and micro RNAs might be critical for early development. The findings suggest that the rich repertoire of coding and non-coding RNAs in stallion sperm is not a random remnant from spermatogenesis in testes but a selectively retained and functionally coherent collection of RNAs.

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Section: Discussionmentioning

confidence: 99%

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding and Regulatory RNAs as Revealed by Microarray Analysis and RNA-seq

et al. 2013

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“…These results raise the possibility that CFTR may play a role during capacitation (Wang et al. , 2003) and it was proposed that CFTR could thereby change its conformation from a closed to an open state thus regulating HCO 3 − entry (Florman et al. , 2007).…”

Section: Discussionmentioning

confidence: 99%

Early activation of sperm by HCO3− is regulated hormonally in the murine uterus

Mannowetz

Wandernoth

Hornung

et al. 2010

International Journal of Andrology

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Sperm deposited in the female genital tract receive signals for capacitation. Past work indicates that HCO(3) (-) is the initiating signal that the female reproductive tract contains the HCO(3) (-) -permeant anion channel cystic fibrosis transmembrane conductance regulator (CFTR) and that mutations in CFTR cause subfertility in both sexes. In this study, we examined whether CFTR controls uterine HCO(3) (-) content and sperm responses to it. Both CFTR protein and mRNA were absent in prepubertal murine uterus, but appeared in pubertal and adult tissues. Thus, CFTR is upregulated during development. Uterine CFTR mRNA additionally increased upon induced oestrus, most abundantly in uterus body and distal horns. Uterine fluid of oestrous females contained two-, and nearly fourfold more HCO(3) (-) than that of dioestrous and prepubertal animals, correlating with increased CFTR expression. For sperm incubated in and recovered from prepubertal uteri, flagellar beat frequency was no different from that before incubation. However, for sperm recovered from dioestrous and oestrous uteri, beat frequency was two- and fourfold higher, respectively. Thus, uterine HCO(3) (-) content may have physiological consequences for sperm motility. The male reproductive tract showed no regional distributions or developmental dependence of CFTR expression. Although the sperm flagellum showed CFTR immunoreactivity, CFTR blockers GlyH-101 or CFTR(inh) -172 did neither diminish HCO(3) (-) -evoked increases in sperm motility nor protein tyrosine phosphorylation. Our results indicate that in the uterus, both CFTR expression and the supply of HCO(3) (-) are upregulated hormonally. We propose that these changes coordinate ovulation with increases in sperm motility and promote other components of capacitation by pathways that do not require CFTR in sperm.

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“…CCK receptors regulate protein phosphorylation (Florman et al 2007). There is good evidence that the cystic fibrosis transmembrane conductance regulator (CFTR), initially described as a Cl K channel, may be involved in the transport of sperm HCO 3 K (Xu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Cholecystokinin receptors regulate sperm protein tyrosine phosphorylation via uptake of HCO3−

Zhou

Shi

et al. 2015

Reproduction

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Cholecystokinin (CCK), a peptide hormone and a neurotransmitter, was detected in mature sperm two decades ago. However, the exact role of CCK and the types of CCK receptors (now termed CCK1 and CCK2) in sperm have not been identified. Here, we find that CCK1 and CCK2 receptors are immunolocalized to the acrosomal region of mature sperm. The antagonist of CCK1 or CCK2 receptor strongly activated the soluble adenylyl cyclase/cAMP/protein kinase A signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation in dose-and time-dependent manners. But these actions of stimulation were abolished when sperm were incubated in the medium in the absence of HCO 3 K . Further investigation demonstrated that the inhibitor of CCK1 or CCK2 receptor could accelerate the uptake of HCO 3 K and significantly elevate the intracellular pH of sperm. Interestingly, the synthetic octapeptide of CCK (CCK8) showed the same action and mechanism as antagonists of CCK receptors. Moreover, CCK8 and the antagonist of CCK1 or CCK2 receptor were also able to accelerate human sperm capacitation-associated protein tyrosine phosphorylation by stimulating the influx of HCO 3 K . Thus, the present results suggest that CCK and its receptors may regulate sperm capacitation-associated protein tyrosine phosphorylation by modulating the uptake of HCO 3 K .Reproduction (2015) 150 257-268

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What can we learn about fertilization from cystic fibrosis?

Cited by 11 publications

References 17 publications

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding and Regulatory RNAs as Revealed by Microarray Analysis and RNA-seq

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding and Regulatory RNAs as Revealed by Microarray Analysis and RNA-seq

Early activation of sperm by HCO3− is regulated hormonally in the murine uterus

Cholecystokinin receptors regulate sperm protein tyrosine phosphorylation via uptake of HCO3−

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