The acrosome of eutherian mammals

Abstract

The acrosome is not just a bag of enzymes, most of which, if not all, are singly non-essential for sperm-oocyte interaction. The Golgi-derived acrosomal cap reveals some extraordinary development and structure particularities. The acrosome of eutherian spermatozoa basically consists of two parts, the anterior and equatorial segments; the present review is devoted to the former, the initial actor in fertilization. Its occasional fanciful morphological changes during epididymal maturation are analyzed, together with its heterogeneous contents: enzymes, zona binding proteins, structural proteins (matrix) and yet to be chemically characterized crystalloids. The plasma and acrosomal membranes present stabilized ordered domains, whereas glycoprotein-free areas appear during capacitation and before fusion. Exocytosis, induced by the cumulus oophorus and/or the zona pellucida, may generally start proximally and progress anteriorly, resulting in the detachment of a hybrid membrane shroud, whose entity is probably maintained by the bound matrix. Immediately released soluble enzymes must be active during the first interactions of the gametes, whereas other lysins, bound to the matrix or stored as proenzymes, are only progressively released. Zona binding is probably achieved via the shroud and/or the IAM (depending on species). Penetration along an incurved slit through the stratified zona is allowed by the rigid and denuded head tip and flagellar hyperactivity, and assisted by the local proteolytic activity of proteasomes bound to the IAM, the unique essential zona lysin system.

Knockout of family with sequence similarity 170 member A (Fam170a) causes male subfertility, while Fam170b is dispensable in mice†

“…To confirm this, the full-length mouse FAM170A sequence with a C-terminal FLAG (cFLAG) epitope tag ( Figure 2A ) was cloned under the CAG promoter in the pCAG1.1 vector and transfected into COS-7 cells. An anti-GOLGIN-97 antibody was used to label the trans-Golgi network in case FAM170A was an acrosome protein, as the acrosome is Golgi-derived organelle [ 47 ]. Using an anti-FLAG antibody to label the FAM170A-cFLAG construct and counterstaining with DAPI to label nuclei, FAM170A localized to the nucleus ( Figure 2B ).…”

The Acrosomal Matrix

“…Phospholipase A2, group III (PLA2G3), which is secreted in the proximal (caput) region of the mouse epididymis, is reported to have a role in epididymal maturation of sperm (Sato et al 2010); however, the Pla2g3 gene is also expressed in the testis, so it is difficult to attribute the subfertility of Pla2g3 −/− males to the lack of the Pla2g3 protein in the epididymis rather than the testis. The molecular mechanisms for these structural alterations are not fully understood but could be due, in part, to changes in protein disulfide cross-links, oligosaccharide modifications, and/or repackaging of the acrosomal components (Anakwe et al 1991; Setiadi et al 1997; Fléchon 2015). …”

“…Some reports refer to the acrosomal matrix as a particulate compartment of the acrosomal contents (Buffone et al 2008). Others make reference to a crystalloid nature observed by transmission electron microscopy (Fléchon 2015). Still others classify the acrosomal matrix as an amyloid (Guyonnet et al 2014).…”

FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice

“…round-headed sperm, is a rare condition characterized by defects in acrosome biogenesis during spermiogenesis ( Kullander and Rausing, 1975 ; Schirren Sen et al, 1971 ). The acrosome is a large, sperm-specific organelle filled with degradative enzymes and receptors that facilitate sperm–egg interactions ( Fléchon, 2016 ; Okabe, 2016 ). Although acrosome formation has been described at light- and electron-microscope levels for decades, the molecular mechanisms of acrosome formation are still being elucidated ( Khawar et al, 2019 ; Leblond and Clermont, 1952 ).…”