Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: Intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage‐gated channels, methylation/acetylation, and transcription factors

Abstract

As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic.

Sperm-borne microRNA-34c is required for the first cleavage division in mouse

“…The importance of sperm miR-34c on first cleavage shown here seems to contradict the observation that crosses between heterozygous males with female mice lacking maternal Dgcr8 produce a normal number of Dgrc8 −/− blastocysts with the appropriate number of blastomeres (11). The discrepancy might result from the fact that spermatogenic cells are connected by intercellular cytoplasmic bridges that allow transfer of regulatory molecules among spermatogenic cells (33). Thus, Dgrc8-deficient sperm from heterozygous males could carry miRNAs or their precursors produced during spermatogenesis.…”

Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development

“…The stabilization of miRNAs can be achieved through binding to circular RNAs or mRNAs (Aravin et al, 2007;Peng and Lin, 2013). Third, the cytoplasm of pachytene spermatocytes and developing spermatids are interconnected through intercellular bridges (IBs) (Haglund et al, 2011;Hermo et al, 2010). IBs allow for sharing of the cytoplasmic contents, including organelles and mRNAs (Ventela et al, 2003).…”

Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload

“…The function of this accumulated iron is unknown, but it can be speculated that it is used for the meiotic cell divisions that these cells undergo and for mitochondrio-genesis. The number of mitochondria increase progressively from the primary spermatocyte to the early acrosomal spermatid stage (8,15), a process requiring iron for mitochondrial iron sulfur cluster and heme synthesis. Therefore, it makes sense that the ferritin concentration decreases toward the SFT lumen (Fig.…”

“…During the final steps of spermatid maturation by elongating spermatids, many mitochondria are shed into residual bodies that are phagocytosed by SC. At this stage the number of mitochondria per spermatid is reduced from several thousands to less than 100 (15), which implies that large amounts of iron are transferred from elongating spermatids to the apical area of SC. The appearance of DMT1 in elongating spermatids correlates with the mitochondrial segregation between midpiece and residual bodies in these cells (21), but a role for DMT1 in that location is not clear.…”