Lamin A/C proteins in the spermatid acroplaxome are essential in mouse spermiogenesis

Abstract

Spermiogenesis is a complex process of terminal differentiation that is necessary to produce mature sperm. Using protein expression profiles of mouse and human testes generated from our previous studies, we chose to examine the actions of lamin A/C in the current investigation. Lamin A and lamin C are isoforms of the A-type lamins that are encoded by the LMNA gene. Our results showed that lamin A/C was expressed in the mouse testis throughout the different stages of spermatogenesis and in mature sperm. Lamin A/C was also expressed in mouse haploid germ cells and was found to be localized to the acroplaxome in spermiogenesis, from round spermatids until mature spermatozoa. The decreased expression of lamin A/C following injections of siRNA against Lmna caused a significant increase in caudal sperm head abnormalities when compared with negative controls. These abnormalities were characterized by increased fragmentation of the acrosome and abnormal vesicles, which failed to fuse to the developing acrosome. This fragmentation also caused significant alterations in nuclear elongation and acrosome formation. Furthermore, we found that lamin A/C interacted with the microtubule plus-end-tracking protein CLIP170. These results suggest that lamin A/C is critical for proper structural and functional development of the sperm acrosome and head shape.

Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

“…With this work, it was possible to add to and confirm previous reports for lamin A/C distribution in mouse testis (Figure 5; Table 1) [28,29]. In fact, lamin A/C is most prominently expressed in the NE of pachytene spermatocytes and the acrosome of elongated mature spermatids.…”

“…For instance, the presence and distribution of A-type lamins (lamins A and C) in mouse testis has been investigated, but the results are inconsistent. Overall, lamin A/C has been described in Sertoli and Leydig cells [27], pachytene spermatocytes [28] and in the perinuclear region of elongated spermatids [28,29]. Nonetheless, Shen and colleagues have shown that the decreased expression of lamin A/C caused a significant increase in sperm head abnormalities [29].…”

“…Overall, lamin A/C has been described in Sertoli and Leydig cells [27], pachytene spermatocytes [28] and in the perinuclear region of elongated spermatids [28,29]. Nonetheless, Shen and colleagues have shown that the decreased expression of lamin A/C caused a significant increase in sperm head abnormalities [29]. In addition, a rodent meiosis-specific A-type lamin, the isoform C2, was found to regulate chromosome dynamics and to promote efficient homologous recombination in mouse [30,31].…”

Formation and function of the manchette and flagellum during spermatogenesis

“…The basic platform of the manchette consists of microtubules and actin filaments. Actin and the associated motor protein myosin play an important role in, e.g., vesicle transport and shaping the spermatid head due to their functional roles in the acroplaxome and manchette (Sun et al 2011, Shen et al 2014. Disassembly of the manchette occurs around steps 13-14 prior to the sperm tail mid-piece formation.…”

Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility

“…In the earlier stages of spermiogenesis, two NE proteins have been implicated in the attachment of the acrosomal vesicle to the anterior NE margin of spermatids, namely lamin A/C (Shen et al ., ) and DPY19L2 (Table ; Fig. ) (Pierre et al ., ).…”