Sperm and egg cells are formed during a process called meiosis. During meiosis, chromosomes from each parent pair-up and swap pieces of DNA in a process called crossover. Crossover is a natural part of meiosis, but mistakes during this process can cause aneuploidy, which can result in infertility, miscarriage or certain genetic conditions such as Down's syndrome.
To better understand how crossover between chromosomes is regulated, researchers at the Blavatnik Institute at Harvard Medical School published two studies – one in Nature, focusing on crossover in human sperm cells, the other in Current Biology, focusing on crossover in worm egg cells.
'The genome of each individual sperm tells a detailed story about human inheritance - what went well, what went wrong, what went differently than in other sperm,' said, leader of the sperm cell study, Professor Steven McCarroll. 'Collectively, tens of thousands of such stories teach us a lot about the meiotic processes and their vulnerabilities.'
The study analysed crossovers and aneuploidy at the same time on all chromosomes in a total of 31,228 sperm cells from 20 donors using a new genome-wide sequencing tool, Sperm-seq, which allowed the team to detect every crossover in every sperm cell, a total of 813,000. The analysis showed that the number of aneuploid sperm ranged from one to five percent from person to person, with an average of 2.5 percent of sperms presenting with aneuploidy. They also found individual sperm with many other kinds of genetic abnormalities.
'We wanted to get a baseline for 'the male factor' in human infertility and reproductive health, namely, how often aneuploidy occurs in sperm,' said lead author of the Nature paper, Dr Avery Davis Bell, 'Expanding knowledge about how people have different sperm aneuploidy rates could further assist sperm banks and fertility clinics as they try to maximise sperm viability and improve prospective parents'.
The researchers discovered that the crossovers varied across sperm cells and people in terms of number, location and spacing on the chromosomes. In addition, sperm cells with many crossovers, appeared to be closer together and more often in the centre of chromosomes. Aneuploidy also occurred at different rates and different stages of meiosis from chromosome to chromosome and from person to person. Based on their results, the researchers suggest that a single biological process helps regulate the number, location and spacing of crossovers.
The second study helps explain why crossovers occur more often in some locations along chromosomes than in others. The researchers found that mistakes in crossovers occurred more often in the middle, or at the far ends of chromosomes, suggesting that egg cells limit crossovers in those areas and allow them where aneuploidy is less likely to result.
'It's terrific to see how findings in male and female meiosis and in different species can complement and inform each other,' said Professor Monica Colaiácovo lead author of the Current Biology paper.
Both studies are an important step towards discovering the regulation of crossovers and why and how their rates differ between reproductive cells and people. In turn this has implications in understanding human reproduction and improving reproductive health.