Tag Archives: testis

For all the damage they cause, viruses also help push evolution

“What we learn from our study is that, in general, viruses have major roles in driving evolution,” one researcher explained. “In the long-term, viruses have positive impacts to our genome and shape evolution.”

While the general principles of evolution are fairly straightforward, the details behind the process is immensely complex. What if someone told you, for instance, that viruses help fine-tune evolution; that these dreaded organisms that aren’t really organisms can help push the survival of a species? As weird as it sounds, that’s one takeaway from the two studies published by the Cincinnati Children’s Perinatal Institute and at Azabu University in Japan.

The scientists looked at lab mice and human sex cells, or to be more precise, at the germline cells — the cells that form the egg, sperm, and the fertilized egg that pass on their genetic material to the progeny (offspring).

Specifically, they looked at the set of all RNA of these sex cells, something called transcriptomes.

These transcriptomes contained either the male or the female half of chromosomes passed on as genetic materials when species mate. In other words, they define the unique character of sperm and egg as they pass on genetic information to the next generations.

The two published papers look at some of the processes behind these transcriptomes. Satoshi Namekawa, principal investigator on both papers, combined biological testing of mouse models and human germline cells with computational biology to see how genes are produced and reorganized following sexual reproduction. He found that a key element in this process is something called super-enhancers.

“One paper, Maezawa and Sakashita et al., explores super-enhancers, which are robust and evolutionally conserved gene regulatory elements in the genome. They fuel a tightly regulated burst of essential germline genes as sperm start to form,” Namekawa said.

Super-enhancers are regulated by two molecules that act as gene control switches. This is where the second study comes in, Namekawa explains.

“The second study, Sakashita et al., involves endogenous retroviruses that act as another type of enhancer – gene regulatory elements in the genome – to drive expression of newly evolved genes. This helps fine tune species-specific transcriptomes in mammals like humans, mice, and so on.

Endogenous retroviruses are normal components of the human genome and account for around 8% of our DNA — in fact, they account for over 5% of many mammals’ DNA. Also referred to as “jumping genes”, these retroviruses have traditionally been considered threats because they can disrupt some genes. However, over the past few decades, researchers have found that these viruses can actually act as regulatory elements for our genome.

This is exactly what Namekawa and colleagues have found. Endogenous retroviruses can help fine-tune transcriptomes, essentially helping a species’ evolution and diversity.

Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition, Nature Structural & Molecular BiologyDOI: 10.1038/s41594-020-0488-3 

Cross section of newborn mouse's testis (Ø = 20 µm), where we can see the seminiferous tubules (red) surrounded by macrophages (green). Confocal micrograph. © Noushine Mossadegh-Keller and Sébastien Mailfert / CIML

New insights into testicular macrophages, the guardians of male fertility

Two types of testicular macrophage — important cells of the immune system — have been described in great detail by French researchers at the Centre d’Immunologie de Marseille-Luminy. These specialized cells that recognize, engulf and destroy target cells are believed to act like a sort of guardians of fertility. As such, this effort will help us better understand what causes male infertility and might lead to innovative treatments.

Cross section of newborn mouse's testis (Ø = 20 µm), where we can see the seminiferous tubules (red) surrounded by macrophages (green). Confocal micrograph. © Noushine Mossadegh-Keller and Sébastien Mailfert / CIML

Cross section of newborn mouse’s testis (Ø = 20 µm), where we can see the seminiferous tubules (red) surrounded by macrophages (green). Confocal micrograph. © Noushine Mossadegh-Keller and Sébastien Mailfert / CIML

Our immune system is critical to our survival. This is why AIDS is such a terrible disease — it’s not the infection itself that kills you but everything else that would normally fly by since the immune system is now superseded. Its primary role is to 1) distinguish native cells and 2) identify, then seek and destroy potentially pathogen foreign cells.

Meet the sperm guard

Technically, though, spermatozoa are also foreign cells. It can take at least a dozen years before puberty sets in and sperm is finally produced by the male testis. Typically, the sperm should be identified as an intruder by certain immune system elements and destroyed. Obviously, this doesn’t happen otherwise there would be no more babies in the world, or you and me for that matter.

This is where the testicular macrophages come in. A macrophage is a large white blood cell which gobbles foreign pathogens like bacteria. Not only do they act as antimicrobial warriors, they also play critical roles in immune regulation and wound-healing. Macrophages exist in nearly all tissues and are produced when white blood cells called monocytes leave the blood and differentiate in a tissue-specific manner. Depending on where they’re made and where they function, macrophages come in different types and bear different names. For example, macrophages present in the brain are termed microglia and in the liver sinusoids they are called Kupffer cells.

In human male testicles, scientists have identified two types of macrophages, each originating in one of the two compartments of the testis. In the so-called interstitial space, where we can find the testosterone-producing Leydig cells, one type of interstitial macrophages is produced. These are made from embryonic cells and are present from the beginning of an individual’s life. The other kind of macrophage is peritubular, named so because we can find it on the surface of seminiferous tubules that house sperm cell precursors.

Studying mice, the French researchers led by Michael Sieweke found peritubular macrophages only appear two weeks after the mice were born, which coincides with the rodent’s puberty. After puberty sets in, the peritubular macrophages stay with them for the rest of their lives, as reported in the Journal of Experimental Medicine.

“We show that embryonic progenitors give rise to the interstitial macrophage population, whereas peritubular macrophages are exclusively seeded postnatally in the prepuberty period from bone marrow (BM)–derived progenitors. As the proliferative capacity of interstitial macrophages declines, BM progenitors also contribute to this population. Once established, both the peritubular and interstitial macrophage populations exhibit a long life span and a low turnover in the steady state,” the authors wrote.

Sieweke’s team now wants to focus on the relationship between macrophages, sperm, and testosterone production. This investigation might one day enable innovative treatments for certain kinds of male infertility.