A new study from researchers at the University of Colorado Boulder found evidence linking to what many scientists have known for decades: overpopulation can impair reproduction.
The study, published earlier this month in the journal Nature Communications, identified one key mechanism explaining why overpopulation can impair fertility in animals, including humans.
According to the study, researchers found that overcrowded animals secrete a chemical messenger that can damage eggs, impair embryos and cause genetic mutations in offspring for future generations.
Senior author Ding Xue, a professor of molecular, cellular and developmental biology at CU Boulder, had this to say about the finding.
“It has been well documented that population density has a direct and negative impact on human and animal fertility, but the underlying mechanisms have been elusive. Our study provides novel insights into how overpopulation can cause various developmental defects, including reduced fertility and increased mortality.”
Because worldwide birth rates have been declining since 1950 – the fertility rate has gone from five births per woman in 1950 to 2.3 births in 2021 – the World Health Organization (WHO) now says one in six people experience infertility, according to CU.
Infertility is defined as the inability to achieve a pregnancy after 12 months of trying.
“Overpopulation and crowding stress have emerged as major challenges in contemporary societies, especially in urban cities, where two-thirds of the world population live,” Xue said. “Our study may provide important molecular insights into the underlying health problems that can come with it.”
Commonalities between radiation and overcrowding
While studying a phenomenon known as radiation induced bystander effect (RIBE), Xue’s team stumbled upon the findings by happenstance, according to CU.
CU said RIBE occurs in cancer patients receiving radiation therapy, but when untreated, healthy cells outside a radiated site are also affected and damaged, leading to side effects like hair loss, fatigue and reproductive issues. Due in part to concerns about RIBE, pregnant women are advised to avoid radiation exposure.
According to CU, in a 2017 study published in Nature, Xue discovered what drives this bystander effect in the Caenorhabditis elegans or C. elegans worm.
Cells stressed by radiation release a protein called cysteine protease related 4 (CPR-4), which travels to other healthy cells around the body and damages their DNA.
Other species of animals, including humans and mice, have a similar chemical messenger called Cathepsin B cysteine protease, CU said.
In a follow-up study years later, Xue’s team noticed that even in the absence of radiation, if worms lived in extremely crowded conditions, they emitted the protein.
Xue said, when looking at the data at the molecular level, the crowded animals looked a lot like they had been exposed to radiation.
Mutations passed through generations
According to CU, for the new study the team compared worms living in various-sized colonies, looking for signs of more or less enzyme secretion based on the size of the colony.
They found the worms typically didn’t secrete CPR-4 in a smaller colony, but once their colony exceeded 3,000 individuals, they did.
The more overcrowded the worms were, the more of the enzyme the worms secreted, with the enzyme damaging their DNA, CU said. Experiments in mice showed similar results.
Xue’s team also found that on average, those living in crowded conditions had 87% more genetic mutations in germ cells (reproductive cells), and the animals had significantly fewer offspring.
Of note, the surviving offspring often had visible defects as well, CU said.
Furthermore, genome sequencing showed some of those genetic mutations were passed on through generations, suggesting overcrowding may drive genome evolution, CU said.
When the researchers silenced the protein in the worms, it prevented the adverse effects of crowding. This action suggested the enzyme played a critical role in reproductive problems, CU said.
More research is necessary to determine whether the findings have implications for humans and other animals, CU said.
Xue has already developed and patented a compound that can inhibit the Cathepsin B cysteine protease enzyme in animals and has a good safety profile.
Xue thinks such inhibitors could be used in agriculture to increase egg or fish production. The findings could also inform new approaches to helping humans struggling to have a family.
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