“Life is a box of chocolates; you never know what you’re gonna eat” is a famous line in the movie Forrest Gump. This principle also applies in human genetics, based on the findings of Harvard Medical School as published by Science Daily.
Human genetic diversity
Meiosis is a process where one cell divides twice to produce four cells that contain half the original amount of genetic formation. These cells are the sex cells: eggs in females and sperm in males. During meiosis, DNA mixes and matches in unpredictable and infinite combinations.
While meiosis is essential for reproduction, the authors explained that it is also error-prone. The rates of chromosomes crossover differ among gametes and between the sexes. When DNA crossovers go wrong, it could lead to birth defects, miscarriages, and infertility.
Authors Avery Davis Bell and colleagues said that faulty DNA crossover formation could leave cells with too few or too many chromosomes. The presence of an abnormal number of chromosomes in a cell is called aneuploidy. Instead of the usual 46 chromosomes, aneuploidy may have 46 or 47 chromosomes. This can also lead to conditions, such as Down syndrome. According to the World Health Organization, the estimated incidence of Down syndrome is between 1 in 1,000 to 1 in 1,100 live births worldwide.
The key to improving human reproduction
The team believes that learning how DNA crossovers are regulated is the key to better understanding human reproduction as well as improving reproductive health. Two determine the diverse meiotic outcomes and how they covary in gametes, chromosomes, and humans, the group developed the Sperm-seq.
Sperm-seq is a way of simultaneously analyzing the genomes of thousands of individual sperm. In their study, they analyzed genomes of 31, 228 human gametes from 20 sperm donors. From it, they identify 813,122 crossovers and 787 aneuploid chromosomes.
Crossover and aneuploidy data per donor
Sperm donors had aneuploidy rates that range from 0.01 to 0.05 aneuploidies per gamete.
Bell, who is from Harvard and Broad Institute of MIT’s Program in Medical and Population Genetics, said that they wanted to get a baseline for the male factor in reproductive health and human infertility or how often aneuploidy happens in sperm.
They needed to analyze the 31,228 human gametes to generate robust statistics and no technology exists yet that could easily do the analysis. For their study, Bell used tiny droplets from a large number of individual cells and then further developed it to study sperm cells. This is why they dubbed their approach Sperm-seq.
Importance of study to fertility clinics and sperm banks
The authors said that expanding the knowledge about how people have different aneuploidy rates will assist fertility clinics and sperm banks as it can improve the fertility of prospective parents and maximize sperm viability.
The Harvard researchers suspect that the variations are driven by which chromosomes get compacted during the meiosis. They also found that the spacing, location, and several crossovers vary together across people and sperm cells. In cells with plenty of crossovers, the crossovers tend to be located proportionately in the central regions of the chromosomes than at the ends and they are closer together. Bell told Science Daily that seeing the same patterns in cells and people is interesting because it suggests the underlying regulation.
It was also discovered that aneuploidy occurs at different stages of meiosis and different frequencies. Although infertility can result from either partner, most treatments nowadays focus on the egg side. This is because eggs are known to have higher aneuploidy rates than sperm since little can be measured about sperm beyond motility and counts.
Nevertheless, the contribution of sperm genetics to miscarriages and infertility has been relatively understudied, Bell said.
According to statistics provided by the US Department of Health and Human Services (HHS), about 12 to 13 of 100 couples in the US have trouble becoming pregnant. About 6.1 million or ten in 100 women in the US ages 15 to 44 have difficulty becoming pregnant or staying pregnant.
Infertility is defined as not being able to become pregnant after having regular intercourse (sex) without birth control after one year or after six months if a woman is already 35 years or older. Meanwhile, the Fertility Center of San Antonio shared that causes of male infertility are typically related to either obstruction or production of sperm. The majority or 34% are unexplained, 10% are hypogonadism, 9% are urogenital infection, 8% are undescended testicles, 6% are sexual factors, 5% are immune system factors, and 3% is a systemic disease.
Men suffering from some form of infertility may struggle with self-esteem issues as they are unable to conceive. Such distress can impact the man’s professional and personal relationships, leading to sexual dysfunction, anxiety, and depression.
Children born per woman
Scientific online publication Our World in Data mentioned that there has been a global decline in the fertility rate since 1950. The fertility rate has declined to 2.5 children per woman and the low fertility rates have become the norm in most parts of the world. A huge majority (80%) of the world’s population now live in nations with a fertility rate that is below 3 children per woman. Women in a few countries, home to about 10% of the world’s population, still have more than 5 children.
In 2019, countries with high fertility rates based on the number of kids born per woman included Niger (7.07 children per woman), Mozambique (5.05), Angola (5.48), Democratic Republic of Congo (5.82), Somalia (5.98), Mali (5.79), Nigeria (5.32), and Uganda (5.32), among others.
A second study highlighted by Science Daily looked at meiosis in developing worm egg cells. The findings were from the lab of Harvard Medical School professor of genetics Monica Colaiácovo. They found that DNA crossovers occur more often in some locations along the chromosomes than in others. "It's terrific to see how findings in male and female meiosis and different species can complement and inform each other," the professor said.
Colaiácovo explained that their study is the first direct demonstration in multicellular animal (metazoan) that shows how the position of crossovers need to be tightly regulated to avoid aneuploidy and ensure the normal chromosome segregation.
It is important to know these basic biological mechanisms and how they function so scientists can better understand what happens when they go wrong and how to lessen the incidence of these errors to prevent birth defects and miscarriage.