spermatogenic Musings

First wave chapter images.001a.jpg

What is the first wave of spermatogenesis?

August 6, 2018

The postnatal process of mammalian male gametogenesis that begins with the differentiation of the first subset of spermatogonia and culminates with the formation of the first spermatozoa is called the first wave of spermatogenesis. As depicted above (P=postnatal day) for mice, it is during this first wave that fundamental cell populations are formed, the seminiferous epithelium matures, and macromolecular structures such as the blood-testis barrier are built that are required for lifelong fertility.

In general, shorter-lived mammals such as rodents initiate and then complete the first wave of spermatogenesis sooner than longer-lived mammals. The life of a rodent outside of the laboratory is perilous and often rather short due to constant threats of predation from birds, snakes, fish, and other mammals; a shortened time to sperm production ensures that rodents are fertile earlier in their lifespan. This maximizes the chances for productive mating encounters that result in pregnancy, which ensures passage of a male rodent’s genes on to the next generation.

However, is this first wave unique to rodents? I don’t think so, and will make the case in the next post that, although it occurs at widely variable times during development, a first wave must occur in all male mammals.

Tex14 KO with bridges.jpg

assessing spermatogonial hierarchies

July 23, 2018

Don't believe the image above, it is meant to mislead you. But please keep reading!

The premeiotic and mitotically dividing cells of the postnatal testis (spermatogonia) contain an active stem cell population. These stem cells divide to both maintain their numbers (via self-renewal) as well as produce large numbers of committed progenitors. At the end of mitosis, most spermatogonia do not physically separate, but remain interconnected via intercellular bridges to form growing chains, or clones. 

One of the long-held tenets of mammalian spermatogonial development, both in the developing and adult testis, is that singly isolated spermatogonia (As) as well as those in pairs (Apr) have the highest stem cell potential, and this decreases with clone growth (into Aal spermatogonia). This model inversely correlating "stemness" with clone length was first proposed in 1971 in independent reports from Claire Huckins and E.F. Oakberg. The misleading image depicting these configurations is shown above, with bridges traced in yellow.

This ~50-year old hierarchical model has been challenged recently; it has been posited that long clones can fragment into smaller ones. By fragmenting, committed progenitor spermatogonia can 'reverse course' by de-differentiating to regain stem cell potential. However, before we can measure fragmentation of a clone, we must first unequivocally prove that it was a clone. Fortunately, determining whether adjacent spermatogonia are connected in a clone is rather straightforward, and can be accomplished by staining for intercellular bridge components, one of which is the essential germ cell-expressed gene product TEX14. This staining will reveal, beyond an assumption, whether spermatogonia residing close to one another are present (or not) in a clonal configuration.

Why is the above image misleading? Because this PLZF-stained seminiferous tubule whole mount is from a Tex14 KO mouse (generated in Marty Matzuk's laboratory). These mice are infertile and completely lack intercellular bridges; therefore, all spermatogonia are singly-isolated (As) and the appearance of connectedness into clones is simply an illusion.