Tetraspanins, More than Markers of Extracellular Vesicles in Reproduction

Abstract

The participation of extracellular vesicles in many cellular processes, including reproduction, is unquestionable. Although currently, the tetraspanin proteins found in extracellular vesicles are mostly applied as markers, increasing evidence points to their role in extracellular vesicle biogenesis, cargo selection, cell targeting, and cell uptake under both physiological and pathological conditions. In this review, we bring other insight into the involvement of tetraspanin proteins in extracellular vesicle physiology in mammalian reproduction. We provide knowledge regarding the involvement of extracellular vesicle tetraspanins in these processes in somatic cells. Furthermore, we discuss the future direction towards an understanding of their functions in the tissues and fluids of the mammalian reproductive system in gamete maturation, fertilization, and embryo development; their involvement in mutual cell contact and communication in their complexity.

Nicotine self-administration with menthol and audiovisual cue facilitates differential packaging of CYP2A6 and cytokines/chemokines in rat plasma extracellular vesicles

“…Tetraspanins are involved in the molecular organization of the cellular plasma membrane and a number of cellular functions including cell motility and migration 31 – 33 . The members of the tetraspanin family such as CD9 and CD63 are important for the formation and cargo recruitment of EVs.…”

Human Placenta Exosomes: Biogenesis, Isolation, Composition, and Prospects for Use in Diagnostics

“…Exosomes contain various proteins, RNA, and lipids, which can play a crucial role in implementing the biological functions of these nanovesicles [ 110 , 111 ]. Human placenta exosomes obtained from the blood of pregnant women may be used as biomarkers of early pregnancy pathological course in patients without symptoms [ 19 , 24 , 98 , 99 , 100 , 101 , 108 ].…”

Seminal Plasma: Relevant for Fertility?

“…The EVs also contain a very particular load of ncRNA (particularly miRNAs, [ 140 , 159 , 160 ], a matter we shall discuss later. Epididymosomes are tethered to receptors on the sperm plasma membrane via proteins as tetraspanins [ 161 ] or cell-surface glycoproteins involved in cell-to-cell interaction, such as CD44 [ 40 ]. These proteins are up to now mostly used as markers [ 39 , 40 ] despite their roles in the biogenesis, cargo selection and cell targeting of the EVs, or in cell contact and uptake [ 161 ].…”

“…Epididymosomes are tethered to receptors on the sperm plasma membrane via proteins as tetraspanins [ 161 ] or cell-surface glycoproteins involved in cell-to-cell interaction, such as CD44 [ 40 ]. These proteins are up to now mostly used as markers [ 39 , 40 ] despite their roles in the biogenesis, cargo selection and cell targeting of the EVs, or in cell contact and uptake [ 161 ]. Considering the latter, CD44, suggested as an eventual marker for epididymosomes [ 40 ], is the main receptor for hyaluronan, the most conspicuous glycosaminoglycan present in the oviductal sperm reservoir and the expanded cumulus cells [ 105 ], and recognized as interplay between the spermatozoa and its surroundings in crucial events such as colonization of the tubal sperm reservoir or capacitation, as well as sperm location of the oocyte [ 105 ].…”