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.

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

Elegy for a Significant Speck (frozen eggs and embryos)

Eggs in an icescape

Two American fertility clinics reported freezers failing last month, and had thawed to an undisclosed degree. This rare event shocked hundreds of patients who were storing embryos, eggs and ovarian tissue. Maybe it was the equipment that failed or a human error, but responsibility rests on the shoulders of clinics except for major fires or criminal intent out of their control. These freezers have electronic alarms. When Lucinda was managing Cornell’s IVF laboratory she could be called automatically on her cell phone if liquid nitrogen levels fell to critical levels. It never happened. She knew the danger because there can be no recovery for cells that thaw improperly.

A tank may contain over a thousand frozen eggs and embryos. To patients, they are prospective children waiting for the day when they will be called by their parents. Some women can repeat IVF treatment to replace their loss, but not everyone because fleeting years of female fertility soon rob them of the chance to be new mothers of their genetic children. I chose another hard case for my example, who came through a tunnel called cancer to renewed health, but she lost her next best hope from a plunge in temperature. Money from a lawsuit is no compensation to warm this kind of chilled heart.