ArticlePloS one2013
Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 185 citations in OpenAlex.
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- Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment.Veterinary medicine and science · 2026Article
- Extracellular Vesicles in Implantation: Cross-Talk Between the Embryo and Endometrium.Advances in anatomy, embryology, and cell biology · 2026Review
- Extracellular vesicles in bovine reproduction: their journey from gametogenesis to pregnancy.Frontiers in cell and developmental biology · 2026Review
- Characterization of extracellular vesicles at parturition in dairy cows with late-gestation heat stress.JDS communications · 2026Article
- Small extracellular vesicles from follicular fluid as transport carriers ofAnimal reproduction · 2026Article
- [The role of extracellular vesicles in early embryo development and their application in assisted reproductive technologies].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Extracellular vesicles from different regions of the female reproductive tract promote spermatozoa motility and support capacitation.Scientific reports · 2025Article
- Integrating Near-Infrared Spectroscopy and Proteomics for Semen Quality Biosensing.Biosensors · 2025Article
- Menstrual blood serum extracellular vesicles reveal novel molecular biomarkers and potential endotypes of unexplained infertility.Scientific reports · 2025Article
- Review
- The Expression Pattern and Functional Analysis of Extracellular Vesicle Long Non-Coding RNAs from Uterine Fluid During Implantation in Pig.Animals : an open access journal from MDPI · 2025Article
- Oviduct epithelium interactions: roles in sperm selection and embryo quality.Animal reproduction · 2025Article
- The bovine oviductal environment and composition are negatively affected by elevated body energy reserves.PloS one · 2025Article
- Extracellular vesicles in female reproduction: from basic research to application.Animal reproduction · 2025Review
- Extracellular vesicles: key mediators inFrontiers in veterinary science · 2025Review
- The extracellular vesicle tetraspanin CD63 journey from the testis through the epididymis to mature bull sperm.Scientific reports · 2024Article
- Proteomic analysis and in vivo visualization of extracellular vesicles from mouse oviducts during pre-implantation embryo development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Exploring the potential of in vitro extracellular vesicle generation in reproductive biology.Journal of extracellular biology · 2024Review
- Immersed in a reservoir of potential: amniotic fluid-derived extracellular vesicles.Journal of translational medicine · 2024Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
PMCA4, a membrane protein, is the major Ca(2+) efflux pump in murine sperm where its deletion leads to a severe loss of hyperactivated motility and to male infertility. We have previously shown that the PMCA4b splice variant interacts with CASK (Ca(2+/)CaM-dependent serine kinase) in regulating sperm Ca(2+). More recently we detected that PMCA4a isoform, in addition to its presence in testis, is secreted in the epididymal luminal fluid and transferred to sperm. Here we show that Pmca4 mRNA is expressed in both the 4a and 4b variants in the vagina, uterus, and oviduct. Immunofluorescence reveals that PMCA4a is similarly expressed and is elevated during estrus, appearing in the glandular and luminal epithelia. Western analysis detected PMCA4a in all tissues and in the luminal fluids (LF) of the vagina (VLF), uterus (ULF), and the oviduct (OLF) collected during estrus. It was ~9- and 4-fold higher in OLF than in VLF and ULF, and only marginally present in LF collected at metestrus/diestrus. Fractionation of the LF collected at estrus, via ultracentrifugation, revealed that 100% of the PMCA4a resides in the vesicular fraction of the ULF and OLF. Transmission electron microscopy (TEM) revealed that OLF vesicles have an exosomal orientation (with the cytoplasmic-side inward), a size range of 25-100 nm, with the characteristic CD9 biomarker. Thus, we dubbed these vesicles "oviductosomes", to which PMCA4a was immunolocalized. Incubation of caudal sperm in the combined LF or exosomes resulted in up to a ~3-fold increase of sperm PMCA4a, as detected by flow cytometry, indicating in vitro uptake. Our results are consistent with the increased requirement of Ca(2+) efflux in the oviduct. They show for the first time the presence of oviductal exosomes and highlight their role, along with uterosomes and vaginal exosomes, in post-testicular sperm acquisition of PMCA4a which is essential for hyperactivated motility and fertility.
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