The sperm centrioles

Abstract

Centrioles are eukaryotic subcellular structures that produce and regulate massive cytoskeleton superstructures. They form centrosomes and cilia, regulate new centriole formation, anchor cilia to the cell, and regulate cilia function. These basic centriolar functions are executed in sperm cells during their amplification from spermatogonial stem cells during their differentiation to spermatozoa, and finally, after fertilization, when the sperm fuses with the egg. However, sperm centrioles exhibit many unique characteristics not commonly observed in other cell types, including structural remodeling, centriole-flagellum transition zone migration, and cell membrane association during meiosis. Here, we discuss five roles of sperm centrioles: orchestrating early spermatogenic cell divisions, forming the spermatozoon flagella, linking the spermatozoon head and tail, controlling sperm tail beating, and organizing the cytoskeleton of the zygote post-fertilization. We present the historic discovery of the centriole as a sperm factor that initiates embryogenesis, and recent genetic studies in humans and other mammals evaluating the current evidence for the five functions of sperm centrioles. We also examine information connecting the various sperm centriole functions to distinct clinical phenotypes. The emerging picture is that centrioles are essential sperm components with remarkable functional diversity and specialization that will require extensive and in-depth future studies.

Keywords: Andrology; Centriole; Male infertility; Semen; Sperm.

Fig 1:. Centriole Remodeling During Early Spermatid Differentiation to Spermatozoa.

A) Early round spermatid encompassed by the cell membrane (CM), with a round nucleus (N), a pair of canonical centrioles (PC and DC), a flagellum made of the axoneme (Ax) cilia membrane (CiM), and the transition zone (TZ) which separates the centriole from the flagellum. The proximal centriole gives rise to a centriolar adjunct (AC). B) Spermatozoon with a flat elongated nucleus (N), a canonical centriole (PC), an atypical centriole (DC), a flagellum made of the axoneme (Ax) cilia membrane (CiM), and decreased amounts of the cell membrane (CM). The annulus/transition zone (An/TZ) separates the flagellum into two parts: a mid-piece and a principal-piece. An inset enlarges the neck with the two centrioles, the capitulum (Ca), and striated columns (SC). C) The Centriolar Complex of early spermatids contains a pair of canonical centrioles (PC and DC) and an axoneme (Ax), pictured from a side view. A cross-sectional view of the proximal centriole consisting of nine triplet microtubules; each triplet microtubule is made up of an A, B, and C tubule. The triplet microtubules are connected by A-C linkers, which attach the A tubule to an adjacent C tubule. The upper part of the PC and DC has a scaffolding structure that connects the microtubules of the centriole. The axoneme is comprised of nine doublet microtubules; each doublet is made of an A and B tubule. Outer and inner dynein arms connect the A tubule of one doublet to the B tubule of an adjacent doublet. The proximal centriole gives rise to a centriolar adjunct (AC). D) The Centriolar Complex of the spermatozoon contains the canonical centriole (PC) atypical centriole (DC), and an axoneme (Ax), pictured from a side view. A cross-section of the proximal centriole made of nine doublet microtubules; each doublet microtubule is made of an A and B tubule. The doublet microtubules are splayed out and have rods in the lumen. The upper part of the PC and DC has a scaffolding structure that connects the microtubules of the centriole. The axoneme is also made of nine doublet microtubules; each doublet is made up of an A and B microtubule. Outer and inner dynein arms connect the A tubule of one doublet to the B tubule of an adjacent doublet. Please note that the figures are not to scale and are intended to point out the approximate shape and location of highlighted features.

Fig 2:. The Five Functions of Sperm Centrioles.

A) Two pairs of centrioles mediate cell division (both mitosis and meiosis) during early spermatogenesis; each pair is comprised of a mother centriole (MoC) and a daughter centriole (DoC) surrounded by pericentriolar material (PCM). The two pairs of centrioles act as two centrosomes located at the spindle pole. Each centrosome nucleates the astral microtubules (A-M), which orients the spindle (Sp) relative to the axis of cell division. The chromosomes (Ch) are organized at the central plate during metaphase. B) Distal centriole (DC) forms the sperm tail during spermiogenesis. In the early spermatid, the distal centriole docks to the cell membrane (CM), nucleates the axoneme (Ax), and initiates the formation of the cilia membrane (CiM). The proximal centriole (PC) is attached to the distal centriole perpendicularly through its sidewall, and it contains an axoneme-like structure that is usually only found during the early spermatid stage called the centriolar adjunct (CA). In the spermatozoon, the annulus/transition zone (An/TZ) migrates to the tail. C) The centrioles play an essential role in linking the head and tail together in the spermatozoon. There are three known subtypes of breaks in this link: a subtype one break is a separation between the head containing the proximal centriole and tail that contains the distal centriole; a subtype two break is a separation between the head containing both the proximal and distal centrioles and the tail that contains most of the axoneme; a subtype three break is a separation between the head and the tail that contains both the proximal and distal centrioles (Nie et al., 2020). D) The centrioles perform a critical role in controlling the movement of the sperm tail. The sperm tail beating starts at the proximal and distal centriole found in the neck, and a wave is propagated down the flagellum. E) The centrioles have a role in organizing the zygote’s cytoskeleton - they form the astral microtubules (A-M) that mediate pronuclei migration and assist in cell cleavage.

Fig 3:. Canonical Centriole Formation, Structure, and Function.

A) Canonical centriole formation. New centriole formation starts with the formation of a Torus structure around the pre-existing mother centriole (MoC). Next, a single cartwheel like structure forms at one spot along the Torus perpendicular to the wall of the mother centriole. Then, the cartwheel develops into a procentriole by forming microtubules (green). The procentriole continues to grow into a daughter centriole (DoC) with an upper scaffold and detaches from the mother wall. The daughter centriole is connected to the mother by a linker complex. Finally, the daughter centriole develops appendages, after which the daughter centriole recruits additional proteins, which stabilize its structure and provide additional functionality (e.g., forming pericentriolar microtubules, astral microtubules, and a flagellum). Proteins involved in centriole formation and are implicated in sperm function are marked in bold at the step they mediate. Please note that the distal appendages are placed on the same level of the MT triplets, and they differ from sub-distal appendages; the number of sub-distal appendages can be from 0 to 14 (Uzbekov and Alieva, 2018). B) Centrosome structure. The centrosome consists of a pair of centrioles (a mother centriole (MoC) and an attached procentriole), centriolar satellites, and pericentriolar material (PCM). A cross-section at the upper part of the mother centriole depicts the presence of an upper scaffold. A cross-section at the procentriole depicts the presence of a cartwheel and A-C linker. C) Flagellum structure. The flagellum consists of a pair of centrioles and the axoneme (Ax). A cross-section shows the upper part of the mother centriole (MoC) and depicts the presence of an upper scaffold. A cross-section at the upper part of the daughter centriole (DoC) depicts the presence of an upper scaffold. A cross-section at the axoneme depicts a central pair running through the axoneme, and inner and outer dynein arms decorate the 9-doublet microtubules.