Category: Biomedical

Biomedicine, especially reproductive medicine, embryology

Androgenic Anxiety and COVID-19

sperm quality
Normal (left) and abnormal forms of sperm

Early this morning, January 1, 2021, three minutes after midnight, the last human being to be born on earth was killed …

Thus begins Children of Men, a dystopian novel by P.D. James (1992). A sudden and unexplained loss of human fertility tipped the world toward apocalypse. Whereas the book held testes to be responsible, the movie version directed by Alfonso Cuaron switched the cause to gynecology, sparing those precious nuts from blame!

It’s possible for a scientist to suspend disbelief in science fiction, but he/ she always prefers to have facts. I had a professional interest in fertility, both female and male. When I first read about a dip in sperm counts, I dismissed it as a statistical quirk or fiction, but no longer. A study combining 185 studies amounting to 42,000 men found average sperm counts have dropped almost 60% in 40 years to 2011 in Western cultures. The trend continues. The paper didn’t report sperm quality (depicted above), a pity because ours is much poorer than in any other species.

The cause is unknown although experts offer similar suggestions to James—lifestyle and/ or pollution. The average count has fallen below 50 million per milliliter, the range of subfertility. While worrying for people who plan to start a family, I wonder what else it portends. Not a plunging population, but possibly raising other alarms if sperm are honest biomarkers.

During development, sperm are shorn of the apparatus that protects and repairs other cells. Short-lived, they only live a couple of days under the best conditions. They could be harmed by toxins in testicular fluids or further along from glandular secretions that contribute to semen. Bad enough if only these specialized cells are harmed, but what if the damage is already done to their stem cell parents? If they are vulnerable to a hidden threat perhaps other cells are affected, and in women as well as men. Could discovery of the affliction of sperm lead to a better understanding of today’s prevalence of some chronic diseases and impacted immune systems?

One in four men who develop mumps have orchitis as fluid builds up to create pressure inside the rigid capsule of testes. Hence, they lose fertility. That the MMR vaccine has greatly reduced the risk of the disease makes the population-wide decline in sperm counts more striking.

But what role for other airborne RNA viruses, especially from the onslaught in recent SARS epidemics and now a pandemic? Cells in testes and ovaries express the ACE-2 receptor, the spike protein that binds the SARS-COVID-19 virus so it can step into cells. A recent study at Columbia University, New York, reported only one covid patient with a low sperm count and virions in his semen, so the risk of infertility or sexual transmission of covid seems slight. Science is still pending a final decision but already concluded the vaccine does no harm to fertility, quashing anxieties in the media.

The human population won’t crash even if every living person became infertile overnight. Vast numbers of semen samples are stored in freezers around the world and frozen cells are good for decades if not centuries. Besides, a few sperm can be found in almost every clinically sterile testis, all that is needed for fatherhood by injecting eggs using the ICSI technique launched the same year as James published her book.

The Sound of Noise & Silence

Among many things we will remember after the coronavirus pandemic, the world was quieter than normal. When I compared a busy avenue-street intersection in Manhattan before and during the lockdown, I found a 6 decibel (dB) difference, four-fold in amplitude. (The vast range of sound detected by the human ear needs the logarithmic scale.) A lower density of traffic on the ground, underground and overhead was mostly responsible, with contributions from building work, human voices, and so on. In suburbia, it is weed whackers, chainsaws, and trucks that make most of the racket, and sometimes neighbors too! You can check out a noise map for your region and community here.

Human ear and listeningI can’t think of any virtues for noise, though we don’t agree on the main offenders. Objections are sometimes muted by vested interests. Noise is in the ear of the beholder. Sounds that some heads perceive as musical turn others in disdain or even pain. I remember marveling at the virtuosity of nightingales singing through the night in Languedoc. The volume can reach 95 dB, above the threshold of harm for human hearing.

… That thou, light-winged Dryad of the trees

In some melodious plot

Of beechen green, and shadows numberless,

Singest of summer in full-throated ease …

John Keats: Ode to a Nightingale

Music is mostly regarded as the antithesis of noise, but commonly causes hearing loss. Rock music at concerts and through headphones, for instance, but players of classical music are also at risk, especially French horn players, and when did you see them wearing ear protection? A trombone and trumpet can even register around 110 dB.

The world gets ever noisier, affecting mental well-being and wildlife. The background soundscape can swamp bird song and amphibian calls needed for wooing mates and defending territories, and sound from shipping and industry is conducted faster and farther through water, harming marine life. Even national parks can be noisy. I registered 65 dB at a car park in Yellowstone and had to hike far from human activity to find a nadir of 30 dB, equivalent to a soft whisper from signing leaves and boughs in still air.

We may seek quiet places for peace, but, please, not too quiet. Plunging below 30 dB is strange and uncomfortable, though few people experience it. When I sat in an anechoic chamber in a lab the ringing in my ears was unpleasant, like so much static (tinnitus). Exploring a labyrinthine cave was probably as silent as outer space, but I never noticed discomfort one day deep underground because I was lost and focused on finding a way out! Just as our brains can blot out noise, they can filter out silence too.

While noise irritates, silence is fascinating, even when it makes us feel uncomfortable. When John Cage’s enigmatic 4’33” composition was performed in 1952, the audience heard the soloist close the piano keyboard for the 3 movements. That’s all, except it wasn’t strict silence—someone coughed and there was a ripple as another suppressed a giggle. Some people interviewed afterwards said they felt insulted or cheated, whereas others said it made them watch and listen more intently than usual. I never heard this composition live, although I often listen in solitude or helped by watching dogs teach alertness to everything around, even when they seem to be dozing. May a quieter planet continue to reign after the pandemic.

 

About Giant Eggs & Double Yolks

This week’s gift from a neighbor’s chicken coop included one extra-large egg. After hard-boiling and cracking open we found a double yolk, which some say is a good omen on our wedding anniversary. The following conversation over a meal would be unlikely in most homes, but perfectly natural in ours.

“Have you ever seen a giant human egg?” I asked my wife, Lucinda Veeck. I have only had a few hundred eggs under my microscope, but Lucinda has examined tens of thousands over a long career in her IVF lab.

Chicken egg with double yolkShe said it happened once. It was obviously immature because there were two nuclei in a cell enclosed by a membranous ‘box’ (the ‘zona pellucida’). A normal egg contains one nucleus and it vanishes shortly before ripening at ovulation by ejecting a surplus set of chromosomes in a cytoplasmic bleb. This elimination is so a fertilizing sperm can add a matched set to restore the pair.

Now here’s the thing. Her giant egg was not a microscopic version of the cooked egg. If a hen bird ovulates two yolky eggs simultaneously, which happens occasionally, they are quickly bathed in albumen, then enclosed in a common membrane and a shell during their journey down the oviduct, a process that takes about 24 hours to laying. As the nuclei are in separate yolks, the outcome is a normal genetic makeup with two chicks hatching from the same egg, although the cramped space affects their viability . The closest parallel is when non-identical human twins are conceived after a double ovulation.

But the nuclei in Lucinda’s giant shared the same cell, so their DNA would be inherited together. Had it been mature for fertilization the embryo would likely have three sets of chromosomes (two female and one male), called digynic triploidy, and fail to develop.

We explored explanations for its origin. If you have seen densely packed eggs in biopsies of young human ovaries you might wonder how they manage to grow independently instead of being swayed by neighbors, like people jostled in a football crowd. Sometimes they lose autonomy. I have seen two or more eggs combined inside follicles of every species examined, up to 14 in dog ovaries, although some looked unhealthy from the competition.

When boxed inside their own membrane eggs can’t fuse to make giant eggs. They have unique genetic makeups, just like eggs from separate follicles that go forward to make non-identical twins. But what happens when they coexist in a ‘box’ and don’t fuse to form a single cell?

Lucinda saw an example five days after an IVF procedure. It was a double embryo at the blastocyst stage with about 64 cells each. If separated for implanting in the womb, it seemed likely they could make non-identical twins, but if they had originated from a fertilized egg that had split instead of from two separate eggs they would make identical twins. It’s possible that they could unite (or reunite) to make a singleton pregnancy, and, if originating from two fertilized eggs, the baby would inherit mixed genetic lineages, a known condition called chimerism.

In the interests of being (somewhat) intelligible, I avoided more abstruse explanations and outcomes. With so many ways that development can go awry, it is a marvel that we turn out well, or mostly, and I am thankful for my genesis otherwise you wouldn’t be reading this post. I usually avoid writing technical stuff, but correspondence is welcome from readers who like to crack eggs.

Next Post: The Sound of Noise & Silence

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