From the father to the offspring, the transmission of genetic information requires careful packaging of the DNA in the sperm. However, the way how this DNA is packaged is still unknown. In a recent study, scientists used new techniques to reveal the three-dimensional organization of DNA in mature male germ cells, revealing a critical period of development that helps explain how fathers pass genetic information to offspring.
Research findings on natural structures and molecular biology by reproductive biologists at the Cincinnati Children’s Hospital Medical Center show that the 3D structure of the DNA is assembled prior to packaging the DNA into the sperm. When germ cells actually become fertile sperm, the genetic material is closely packed. The genetic material of male germ cells has a precise three-dimensional organization in the cell’s genetic control center, the nucleus. Researchers report that this 3D organization is necessary for men to help them create the next generation.
“We propose that male sperm is not just a carrier of DNA. Our data suggest that the three-dimensional organization in the nucleus helps establish a molecular basis that can reproduce a complete fertilized egg that can become the next generation,” the authors claimed. The findings open up the possibility of new research to study how the three-dimensional structure of genetic material affects fertility and premature or stillbirth.
Utilizing mature male mouse germ cells to conduct research on meiosis which is part of the rules of nature, in which male and female mammals each contribute half of their genetic material to produce the next generation of genetically integrated but diverse members. Humans have a total of 46 chromosomes, and the mother and father each contribute 23 chromosomes.
Researchers are able to display 3D tissue and interactions of chromosomes, as well as genes in the meiotic male germ cell nucleus with a technique called Hi-C. The authors suggest that the preparation of 3D tissue in meiosis is critical for allowing germ cells to regain the ability to produce all of the body’s cells after fertilization of female eggs.
“In meiosis, gene expression is very high and diverse,” said Kris Alavattam, a member of the Namekawa lab, the first author of the study. “Many of these genes are essential for the development of germ cells, and many genes are not expressed elsewhere in germ cells, and not at all other times.”
During this time, the genetic material in germ cells is organized in spatially related compartments called genomic compartments. In meiotic male germ cells, the researchers noted that the genomic compartment is weaker than the rest of the body. This weakness helps promote their global reprogramming of so-called 3D chromatin tissue. This chromatin organization – the packaging of DNA and DNA binding proteins – promotes essential gene expression and germ cell development. After meiosis, the chromatin genome encapsulates DNA in a highly organized manner as a cell for preparation for reproduction. In order to gain a deeper understanding of how people can make a contribution to reproductive health issues, scientists now expect to use their laboratory modeling systems to understand how damage to 3D chromatin tissue affects fertility.
Kris G. Alavattam, So Maezawa, Akihiko Sakashita, Haia Khoury, Artem Barski, Noam Kaplan, Satoshi H. Namekawa. Attenuated chromatin compartmentalization in meiosis and its maturation in sperm development. Nature Structural & Molecular Biology, 2019; DOI: 10.1038/s41594-019-0189-y