Transport of germ cells across the seminiferous epithelium during spermatogenesis—the involvement of both actin- and microtubule-based cytoskeletons

Abstract

The transport of germ cells from the base of the seminiferous epithelium toward the luminal edge of the tubule lumen in the adluminal compartment during the epithelial cycle is an essential cellular event to support spermatogenesis. Thus, fully developed elongated spermatids (i.e., spermatozoa) can be released at spermiation in late stage VIII in rodents versus late stage II in humans. Earlier studies to examine the molecular mechanism(s) that support germ cell transport, most notably the transport of preleptotene spermatocytes across the blood-testis barrier (BTB), and the transport of elongating spermatids across the adluminal compartment during spermiogenesis, is focused on the adhesion protein complexes at the cell-cell interface. It is generally accepted that cell junctions at the Sertoli cell-cell interface at the BTB, including the actin-based tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific adherens junction) and gap junction (GJ), as well as the intermediate filament-based desmosome undergo constant remodeling to accommodate the transport of preleptotene spermatocytes across the barrier. On the other hand, similar junction dynamics (i.e., disassembly, reassembly and stabilization/maintenance) take place at the Sertoli-spermatid interface. Emerging evidence has shown that junction dynamics at the Sertoli cell-cell vs. Sertoli-germ cell interface are supported by the 2 intriguingly coordinated cytoskeletons, namely the F-actin-and microtubule (MT)-based cytoskeletons. Herein, we provide a brief summary and critically evaluate the recent findings. We also provide an updated hypothetical concept regarding germ cell transport in the testis utilizing the MT-conferred tracks and the MT-specific motor proteins. Furthermore, this cellular event is also supported by the F-actin-based cytoskeleton.

Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons

“…Recent studies have shown that the actin- and microtubule (MT)-based cytoskeletons in the seminiferous epithelium are playing a crucial role to the homeostasis of the BTB in the mammalian testis, in particular the cytoskeletal elements at the basal ES [5–11]. Specifically, it was shown that besides serving as the attachment sites for the adhesion protein complexes at the BTB, these cytoskeletons also provide the track-like structures to support (1) intracellular trafficking of endocytic vesicles and other cargoes (e.g., phagosomes, endosomes) and (2) the paracellular transport of preleptotene spermatocytes connected in clones across the immunological barrier at stage VIII of the epithelial cycle in rodent testes [12–14]. This conclusion is supported based on studies by disrupting these track-like structures such as through a transient knockdown of nucleation protein formin 1 (Fig.…”

Intraflagellar transporter protein 140 (IFT140), a component of IFT‐A complex, is essential for male fertility and spermiogenesis in mice

“…Similar to the conditional Ift20 KO mice, significant amount of cytoplasmic residual bodies and sperm with redundant cytoplasm were discovered in the conditional Ift140 KO epididymides, but these were not seen in the conditional Ift25 and Ift27 mutant mice. As discussed previously, this phenomenon might be caused by a defect in Sertoli/germ cell recognition and failure of residual body formation and Sertoli cell phagocytosis of the excess germ cell cytoplasm (Wen et al 2016). Even though IFT20 and IFT140 are reported to be present in different IFT complexes in Chlamydomonas , with IFT20 in IFT-B complex, and IFT140 in IFT-A complex.…”

“…The two IFT proteins are not required for ciliogenesis in somatic cells (Eguether et al 2014; Yang et al 2015); however, both play essential roles in sperm formation and function (Liu et al 2017; Wen et al 2016; Zhang et al 2017). Residual bodies and redundant sperm cytoplasm were not present in the preparation of the two conditional knockout mice, suggesting that IFT140 has a different role compared to the two IFT molecules.…”

Physiological role of actin regulation in male fertility: Insight into actin capping proteins in spermatogenic cells

“…Spermatogenic cells change their shape dramatically during spermatogenesis, and a tremendous number of proteins and molecules are involved in each phase. Cytoskeletal elements are essential for morphological roles or the translocation of spermatogenic cells to move from the base of the seminiferous tubule toward the luminal edge during spermatogenesis . The eukaryotic cytoskeleton is composed of microtubules, intermediate filaments and actin filaments (microfilaments), and each of these elements is fundamental to eukaryotic cell biology and integral to a diversity of cellular functions .…”

“…Cytoskeletal elements are essential for morphological roles or the translocation of spermatogenic cells to move from the base of the seminiferous tubule toward the luminal edge during spermatogenesis. 2,3 The eukaryotic cytoskeleton is composed of microtubules, intermediate filaments and actin filaments (microfilaments), and each of these elements is fundamental to eukaryotic cell biology and integral to a diversity of cellular functions. 4 Actin filaments, one of the fundamental components of the cytoskeleton, have been revealed to be concentrated in specific regions of both spermatogenic cells and Sertoli cells and to serve as a structural scaffold and track for motor proteins.…”