spermatogenic Musings


How does spermatogenesis work in seasonal-breeding mammals?

August 20, 2018

Most mammals exhibit seasonal breeding behavior. Breeding seasons vary by species and by latitude, but are precisely coordinated with the length of the gestation period so that offspring are born in the most favorable time of the year for their survival. During the breeding season, changes in photoperiod and/or food availability are correlated with activation of the hypothalamic axis and increased serum testosterone levels as well as cyclical growth of the seminiferous epithelium and appearance of the full complement of spermatogenic cells and the production of spermatozoa. Outside of this breeding season, sexual behavior is reduced or absent, testes are small(er), and the seminiferous epithelium regresses to contain Sertoli cells plus spermatogonia and or spermatocytes and perhaps spermatids.

The seasonal growth and regression of the seminiferous epithelium has been characterized at the histological level in multiple species (e.g. grizzly bear, mole, whitetail deer, armadillo, and even some marine mammals); however, the molecular mechanisms underlying these changes are unknown. It seems reasonable to suspect that the well-documented seasonal changes in testosterone levels coordinate and regulate the epithelial changes described above. However, in mice the loss of testosterone signaling (Sertoli cell androgen receptor KO, or SCARKO), causes a meiotic block, which is not mimicked in all of the seasonal breeders, especially those with an earlier block in spermatogenesis, at the spermatogonia stage. It would be a great contribution for a laboratory to closely study spermatogenesis in a seasonal-breeding mammal model using modern technologies (e.g RNA-seq, proteomics, use of signaling inhibitors, hormone manipulation, etc.) to gain a more complete understanding of seasonal breeding regulation in mammals, and insights gained would surely be applicable to non-seasonal breeders such as humans.


Is the ‘first wave of spermatogenesis’ a rodent-specific phenomenon?

August 15, 2018

Chart.jpg

Timing of spermatogenesis in non-seasonal breeding mammals

 

 

From Geyer CB (2017) Setting the stage: the first round of spermatogenesis. Oatley JM, Griswold MD (Eds.), The Biology of Mammalian Spermatogonia, NY, NY: Springer Nature, pp. 39-63.

The short answer to this question is no, of course not!  

At least one first round or wave of spermatogenesis occurs in all mammals. After the completion of the first wave, the testis is filled with the full complement of germ cells (spermatogonia, spermatocytes, spermatids, and spermatozoa), and progression of spermatogenesis is controlled so that production of the first sperm is temporally coordinated with the onset of sexual maturity (~7 weeks of age in mice, 12-13 years in humans). Multiple studies over the past 50-60 years have revealed that what does differ considerably between mammalian species is the timing of initiation of spermatogenesis and the interval following initiation until formation of the first testicular sperm (see summary table, above), which represent the finished product of the first and all subsequent rounds of spermatogenesis.

In seasonal-breeding mammals, a new first wave occurs at the beginning of each breeding season. It is unknown whether this first wave is initiated solely from spermatogonia, or from the latent spermatocytes or spermatids left over from the last breeding season in some species. In non-seasonal breeding mammals, the first wave often proceeds following the formation of type A spermatogonia in an uninterrupted fashion. This is particularly true in rodents, which have no temporal breaks in the first wave of spermatogenesis. This is in sharp contrast with humans, which have long temporal breaks between initiation and completion of the first wave. Human type A spermatogonia (termed Apale and Adark, respectively) form in the infant testis, but then become developmentally arrested (except for a small population of type B spermatogonia that often form around 5-6 years of age) until sexual maturity occurs with the onset of puberty at 12-13 years of age. At puberty, these type A and B spermatogonia presumably continue to develop in an uninterrupted fashion in response to the regulatory endocrine signals such as testosterone (T) and follicle stimulating hormone (FSH).

I argue that studying the first wave of spermatogenesis (which occurs in all mammals) using rodents as a model will uncover the key regulatory molecules and pathways that underlie male mammalian germ cell development in all species, including humans.


What is the 'first wave of spermatogenesis'?

August 6, 2018

  From      Geyer CB    (2017) Setting the stage: the first round of spermatogenesis. In Oatley JM and Griswold MD (Eds.),  The Biology of Mammalian Spermatogonia , New York, NY: Springer Nature, pp. 39-63.

From Geyer CB (2017) Setting the stage: the first round of spermatogenesis. In Oatley JM and Griswold MD (Eds.), The Biology of Mammalian Spermatogonia, New York, NY: Springer Nature, pp. 39-63.

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.


assessing spermatogonial hierarchies

July 23, 2018

Tex14 KO with bridges.jpg

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.