The global birthrate has been steadily declining for decades, with many couples in the U.S. choosing to have children later in life. Data from the U.S. Census Bureau and the National Center for Health Statistics shows a sharp decrease in fertility rates among women aged 20 to 24, which dropped by 43% between 1990 and 2013. However, the number of births among women aged 35–39 increased by 67%, and for women aged 40–44, this rise was nearly 139%.
Women who have children later in life depend on the resilience of their eggs and sperm. One critical factor in this resilience is the piRNA pathway, which helps protect germ cell genomes well into adulthood. The Piwi pathway, activated at puberty, and the expression of transposon RNAs (mobile DNA sequences) play a crucial role in maintaining this protection.
A breakthrough discovery from researchers at Boston University’s Chobanian & Avedisian School of Medicine has revealed an important new function for a protein called Traffic Jam. In fruit flies, Traffic Jam activates a non-coding piRNA gene named Flamenco, which plays a significant role in female fertility. This discovery resolves a 30-year-old mystery about how Flamenco protects the ovaries from retroviral transposons, genetic parasites that can harm the reproductive system. The findings could eventually lead to treatments for infertility in humans.
The research, published in Cell Reports, is the result of a collaboration between Boston University and researchers in France and the UK.
The Role of Traffic Jam in Protecting Germ Cells
The study, led by Dr. Nelson Lau, associate professor of biochemistry at Boston University, suggests that Traffic Jam is vital for activating Flamenco piRNAs. These piRNAs bind to Piwi proteins, safeguarding the germline genome and ensuring the production of fertile eggs. However, the researchers also discovered a surprising twist: retroviral transposons can hijack the Traffic Jam pathway, turning it to their advantage in an ongoing “battle” for genetic survival.
Dr. Lau explains, “Understanding the Traffic Jam’s function in fruit flies can help us investigate infertility in humans. If humans with infertility lack functional sperm, it might be linked to defects in Piwi genes or transcription factors.”
Uncovering Genetic Mechanisms in Fruit Flies
The research team used a series of advanced techniques to explore the gene activity in fruit flies. In 2017, they used luciferase-reporter assays to measure the biological responses and gene activity related to Flamenco. They confirmed the importance of Flamenco’s DNA sequences by creating new fruit fly mutants using CRISPR genome editing. Further proteomics experiments revealed that Traffic Jam binds to Flamenco DNA sequences, leading to the production of protective piRNAs.
These findings are part of ongoing studies that explore the complex relationship between genetics and fertility. Researchers hope that by studying the role of piRNAs in both fruit flies and humans, they can find new ways to address infertility issues in people.
The Human Connection
Dr. Lau points out the striking similarities between humans and fruit flies in terms of reproductive biology. Both species rely on piRNAs to protect their germ cells from transposons. In humans, a gene similar to Traffic Jam, called MAF-B, could play a role in regulating piRNA genes and helping produce functional sperm. Future studies will test whether MAF-B has the same function in humans as Traffic Jam does in fruit flies.
This new discovery not only deepens our understanding of fertility in fruit flies but may one day offer insights into human infertility treatments.
Related topics:
