Biologically speaking, human development begins after the joining of a sperm and an egg. Around 100 years ago, the German biologist Theodor Boveri brilliantly summarised the unique contributions of each gamete, stating: “The ripe egg possesses all of the elements necessary for development save an active division-center. The sperm, on the other hand, possesses such a center, but lacks the protoplasmic substratum in which to operate. In this respect the egg and the sperm are complementary structures; their union in syngamy thus restores to each the missing element necessary to further development. Accepting this it follows that the nuclei of the embryo are derived equally from the two parents; the central bodies [centrosomes] are purely of paternal origin; and to this it might be added that the general cytoplasm of the embryo seems to be almost wholly of maternal origin” (1). Since the human oocyte lacks centrioles, it seems that the embryo centrioles are exclusively paternally inherited.

Figure 1. According to the current dogma, mature sperm cells display a single centriole. The spermatid neck contains a proximal centriole (PC) and a distal centriole (DC). The ejaculated spermatozoon shows a proximal centriole and an empty space, the vault, which marks the location of the degenerated distal centriole. Modified from (2)

The current prevailing dogma claims that, during spermatogenesis, the sperm centrosome is remodelled through a process called centrosome reduction, leaving the mature sperm cell with a single centriole left. Throughout this process, the centrioles of immature spermatozoa and their surrounding pericentriolar material (PCM) are modified, resulting in a vault in place of the distal centriole, along with residual microtubules and proteins (Fig. 1). To date, no functions have been associated with those remnants. Accordingly, mature sperm have a single functional centriole that is provided to the oocyte, therefore the zygote inherits only one centriole. The recently-formed embryo needs two centrosomes to give rise to four centrioles, two for each daughter cell. Since new centrioles form by duplication of pre-existing ones, where does the zygote obtain its second centriole?

A research group at University of Toledo (Ohio, USA) might have found the answer. In a recent study published in Nature Communications (2), they aim to overturn the old dogma by proposing mature sperm actually carries two centrioles. The authors have demonstrated that the sperm centrosome contains, in addition to the known centriole, a surrounding matrix of pericentriolar material and an atypical centriole undiscovered to date.

Using cutting-edge microscopy techniques, it was found that the distal centriole microtubules do not degenerate during spermatogenesis as previously thought. Instead, these are remodelled during spermiogenesis into an atypical centriole. In mature sperm, the distal centriole is found attached to the base of the axoneme, but its microtubules splay outwards. Those splayed microtubules surround previously undescribed rods of centriole luminal proteins, forming a novel atypical structure (Fig. 2).

Human sperm cells have been widely studied since 1677, when Antonie van Leeuwenhoek was captivated by his animalcules (3), becoming the first person to see living sperm cells. Thus, it is surprising that this elusive structure has not been discovered until today. Likely, the second centriole was previously overlooked because it is completely different from the known centriole, in terms of protein composition and structure. It may also have been disrupted by the classical chemical fixation methods used for transmission electron microscopy. Unlike previous studies, Fishman et al (2018) used super-resolution microscopy, electron microscopy with high-pressure freezing and correlative light and electron microscopy (2), which allowed them to see proteins at the highest resolution.

Figure 2. Model of the distal centriole in the ejaculated human spermatozoon, based on electron microscopy, confocal microscopy, and 3D-Structured Illumination Microscopy (3D-SIM). Dc: distal centriole; mt: mitochondria, Sc: striated columns; Ax: axoneme; V: vault. Modified from (2).

Despite the structural differences of this newly discovered centriole, results show that it may function similarly and along with the known proximal centriole. Researchers simulated a fertilisation environment without creating embryos, using a cell-free in vitro system that exposed demembranated sperm to egg extracts from Xenopus laevis. This system demonstrated that the human distal centriole is capable of recruiting PCM protein and γ-tubulin, suggesting its competency. To further investigate the action of this structure, researchers used bovine sperm as a model. Bovine sperm has compositional similarities with human sperm, as well as an increased size that allows for the use of certain microscopy techniques that cannot be used on human material. An additional feature that makes it a suitable model is that sperm cells from the bovine species were also thought to contain only the proximal centrosome. However, following the bovine sperm distal centriole into the zygote, the authors found that a new daughter centriole was formed and localised to the spindle pole during mitosis, all while maintaining its attachment to the axoneme.

Abnormalities in the formation and function of the distal centriole may be involved in currently-known idiopathic forms of male infertility. As a consequence, a better understanding of this newfound structure may help not only to learn more about early human embryonic development, but also to develop new therapies for related infertility issues. In fact, Dr. Avidor-Reiss and his team are currently planning to take this research to the next level, working with urology colleagues to understand the clinical implications of this atypical centriole.

REFERENCES

  1. Wilson EB. The Cell in Development and Heredity. 3d ed. New York: Macmillan; 1925.
  2. Fishman EL, Jo K, Nguyen QPH, Kong D, Royfman R, Cekic AR, et al. Author Correction: A novel atypical sperm centriole is functional during human fertilization. Nat Commun. 2018;9(1):2800.
  3. Van Leeuwenhoek A, Dobell C. Antonie Van Leeuwenhoek and His “Little Animals”. A collection of the writings of the father of protozoology and bacteriology. New York, Dover Publications Inc.; 1960.