Sperm play a critical role within the creation of recent life, delivering essentially half of the genetic material required.

The success of this process relies on the generation of a developmentally competent sperm cell, which is commonly determined by shape. Indeed, during in vitro fertilization, the “best-looking” sperm is chosen to fertilize an egg.

Nevertheless, how this optimal shape translates to proper sperm function is difficult to evaluate due to many confounding aspects.

Researchers on the University of Michigan are actually delving into the molecular-level details of sperm formation, with a selected concentrate on how abnormalities on this process might result in male-factor infertility.

Unlike other cells within the body, sperm possess a singular characteristic-;their genetic material is full of proteins called protamines.

Protamines have been present in various living organisms resembling plants, fish, and mammals, spanning a whole bunch of tens of millions of years of evolution.

The importance of this protamine-based packaging system of sperm cells raises an intriguing query: why do sperm use protamines to package DNA as a substitute of histones, that are employed by all other cell types?

To uncover the importance of protamines in reproduction, Saher Sue Hammoud, Ph.D., Sy Redding, Ph.D., Lindsay Moritz, Ph.D., Samantha Schon, M.D., and their team conducted an in-depth study of the molecular sequence composition of protamines to grasp how variations within the protein effect function.

“We began taking a look at protamines because they’re in lots of animal species and are also rapidly evolving, so there’s a number of sequence variation,” said Hammoud, an associate professor of human genetics, obstetrics and gynecology and urology.

Most mammals have multiple sorts of protamines and these have to be maintained in well-defined ratio, and deviations on this ratio have been related to infertility.

Conventional wisdom has it that protamines are particularly efficient at tightly packaging DNA into dense structures called chromatin because they’re wealthy in arginine, a positively charged amino acid that strongly binds to the negatively charged DNA.

Nevertheless, recent studies have shown that protamines even have non-arginine amino acids which can be species specific and have unexpected post-translational modifications, that chemically change proteins after they’re made.

This study, published within the journal Nature Structural & Molecular Biology, explores previously unrecognized features of protamines.

“The molecules that interact and package DNA are known to have positively charged features. What’s really beautiful about this work is it reveals other logic embedded in these proteins that we never really considered, other amino acids which can be doing very necessary jobs as well,” said Redding, assistant professor of biochemistry and molecular biotechnology on the University of Massachusetts Chan Medical School.

Moreover, what was intriguing was the presence of post-translational modifications on protamines, despite the indisputable fact that sperm should not transcriptionally lively.

“The indisputable fact that protamines have all of those different modifications on them suggests that these modifications will need to have some function in chromatin packaging,” said Moritz, a postdoctoral fellow within the Hammoud Lab and co-first writer on the paper.

Using mice, they analyzed a modified lysine residue specific to a mouse protamine and present in mature mouse sperm. Substituting lysine with an alanine amino acid (which can’t be modified) resulted in abnormally shaped sperm, impaired embryonic development, and reduced fertility.

What’s more surprising was replacing the lysine with a positively charged arginine didn’t correct the defective sperm packaging, meaning the interactions transcend the charge of the molecule.

Male-factor infertility often lacks a transparent cause, which highlights the importance of studying these modifications.

Noted Schon, assistant professor within the U-M Department of Obstetrics and Gynecology and co-first writer on the paper, “I feel these modifications are interesting as one other avenue of research and identifying the reason for infertility, and the indisputable fact that it would play a task within the early embryo has huge significance as a possible diagnostic tool and post-fertilization for IVF.”

The team hopes to next examine the mechanisms of sperm cell packaging in greater detail within the hopes of recreating the method completely in vitro.