Essential Roles of Efferent Duct Multicilia in Male Fertility.

Mohammed Hoque,Danny Chen,Feng-Qian Li,Eunice N Kim,Ken-Ichi Takemaru

doi:10.3390/cells11030341

Abstract

Cilia are microtubule-based hair-like organelles on the cell surface. Cilia have been implicated in various biological processes ranging from mechanosensation to fluid movement. Ciliary dysfunction leads to a plethora of human diseases, known as ciliopathies. Although non-motile primary cilia are ubiquitous, motile multicilia are found in restricted locations of the body, such as the respiratory tract, the oviduct, the efferent duct, and the brain ventricles. Multicilia beat in a whip-like motion to generate fluid flow over the apical surface of an epithelium. The concerted ciliary motion provides the driving force critical for clearing airway mucus and debris, transporting ova from the ovary to the uterus, maintaining sperm in suspension, and circulating cerebrospinal fluid in the brain. In the male reproductive tract, multiciliated cells (MCCs) were first described in the mid-1800s, but their importance in male fertility remained elusive until recently. MCCs exist in the efferent ducts, which are small, highly convoluted tubules that connect the testis to the epididymis and play an essential role in male fertility. In this review, we will introduce multiciliogenesis, discuss mouse models of male infertility with defective multicilia, and summarize our current knowledge on the biological function of multicilia in the male reproductive tract.

Highlights

Cilia are microtubule-based, tiny hair-like organelles that extend from the apical surface of many different cell types [1,2,3]
The ciliary axoneme, which is composed of microtubule bundles with associated proteins, is surrounded by a specialized ciliary membrane that is continuous with the plasma membrane but has distinct properties with unique lipid and receptor compositions [6,7]
Primary cilia are present on many different cell types in the human body and play key roles in mechanosensation, photoreception, and various intracellular signaling pathways, including hedgehog (Hh), platelet-derived growth factor (PDGF), and G-protein-coupled receptor (GPCR) pathways [1,2]

Summary

Introduction

Cilia are microtubule-based, tiny hair-like organelles that extend from the apical surface of many different cell types [1,2,3]. Primary cilia are present on many different cell types in the human body and play key roles in mechanosensation, photoreception, and various intracellular signaling pathways, including hedgehog (Hh), platelet-derived growth factor (PDGF), and G-protein-coupled receptor (GPCR) pathways [1,2]. Downstream of Notch inhibition, the MCC differentiation gene regulatory network is controlled by the coiled-coil Geminin family proteins Geminin (GMNN), Geminin coiledcoil domain-containing protein 1 (GEMC1), and MCIDAS ( known as multicilin or IDAS) [38,39,40,41,42,43,44,45,46]. In airway MCCs, the 15‐kDa coiled‐coil protein Chibby (Cby1) plays an important role in ciliary vesicle formation and basal body docking (Figure 2) [13,63]. Developed cilia are highly dynamic and constantly undergo turnover with continuous transport of proteins and lipids in and out of cilia [72,73]

Male Reproductive Tract and Passage of Spermatozoa through Efferent Ducts

Roles of Multiciliated Cells in Efferent Ducts

Findings

Mouse Models with Defective Multicilia in Efferent Ducts