Abstract
SummaryA low-calcium microenvironment is essential for spermatozoa to mature in the epididymis; however, it remains unclear how dysregulation of epididymal luminal calcium is associated with male infertility. Using a warfarin-induced vitamin K2 deficiency rat model, we found that vitamin-K-dependent γ-glutamyl carboxylase (GGCX) and matrix Gla protein (MGP) were essential in extracellular calcium signaling of the intercellular communication required for epididymal sperm maturation. We found that GGCX and MGP co-localized in the vesicular structures of epididymal cells and spermatozoa. Calcium-regulated MGP binds to proteins in a biphasic manner; sub-millimolar calcium enhances, whereas excessive calcium inhibits, the binding. Bioinformatic analysis of the calcium-dependent MGP-bound proteome revealed that vesicle-mediated transport and membrane trafficking underlie the intercellular communication networks. We also identified an SNP mutation, rs699664, in the GGCX gene of infertile men with asthenozoospermia. Overall, we revealed that the GGCX-MGP system is integrated with the intercellular calcium signaling to promote sperm maturation.
Highlights
Proper intercellular communication is essential for multicellular organisms to function and survive normally, and aberrant exchange of information may result in pathological conditions and diseases
Our study suggests that mutations of g-glutamyl carboxylase (GGCX) or dysfunction of the GGCX-matrix Gla protein (MGP) system in calcium-regulated epididymal sperm maturation is the pathological cause in some infertile men
Dynamic Cellular Localization of GGCX and MGP in the Rat Epididymis As a first step to determine the expression level of the vitamin K (VK)-cycle-associated proteins in the epididymis, realtime PCR method was used, and results showed that the mRNAs of GGCX, MGP, and VKOR complex subunit 1 (VKORC1) were all expressed in the wild-type (WT) rat epididymis, whereas VKORC1L1 was detected at a negligible level (Figure 1A)
Summary
Proper intercellular communication is essential for multicellular organisms to function and survive normally, and aberrant exchange of information may result in pathological conditions and diseases. Spermatozoa have to exchange numerous cellular components by interacting with the epithelial cells that nurture and protect them while they transit through and mature in the epididymis (Dacheux and Dacheux, 2014; Hermo and R.B, 2002; Robaire and Hinton, 2015). The cell-cell cross talk among spermatozoa and the various types of epididymal cell takes place in the luminal microenvironment, in which a unique composition of epididymal fluid is formed and regulated for special needs of these cells, such as metabolic demands (Cornwall, 2009; Robaire and Hinton, 2015; Turner, 2002; Zhou et al, 2018). The physiological roles of the constituents of the epididymal luminal microenvironment, the medium for the communication between spermatozoa and epididymal cells, remain largely unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
