KEY molecule that controls the trafficking of cholesterol inside cells affects their ability to produce steroid hormones that support pregnancy and trigger puberty, according to the results of a study from Washington University School of Medicine, St. Louis, Missouri, USA. The study team say that their findings provide significant clues concerning the causes of infertility and drivers of early puberty, especially in girls.
The researchers suggested that a surplus of the key molecule likely impairs proper steroid hormone production, leading to infertility, while too little may result in premature sperm maturation. The key molecule they determined is U17 snoRNA, a small strand of RNA from a class known as small nucleolar RNA, or snoRNA. “This is one of several hundred snoRNAs,” noted Prof Daniel S. Ory, Professor of Medicine, Cell Biology and Physiology, Cardiovascular Division, Washington University School of Medicine. “Clearly, some of them have functions beyond the traditional understanding of snoRNAs, and perhaps they should be studied more systematically.”
In this study, the team revealed that at birth, mice have high levels of U17 snoRNA in their ovaries and testes, which gradually decrease as they mature. When the mice reach sexual maturity – at 8 weeks – U17 snoRNA levels are very low and this boosts production of steroid hormones.
Prof Ory explained: “The ovaries need to make steroids to support pregnancy when the mice reach sexual maturation. So we think this small RNA is at least one of the regulators of the processes that govern when a mouse becomes fertile.”
The team then investigated hamster ovary cells, paying special attention to cholesterol and mitochondria. They found that in cells lacking U17 snoRNA, cholesterol was directed into the cell’s mitochondria; however, in cells with an abundance of U17 snoRNA, the cholesterol did not reach the mitochondria, and without their raw ingredients the cells did not produce steroids. When the team adjusted U17 snoRNA levels in normal, immature mice, cholesterol was able to travel to the mitochondria, triggering steroid production in the mouse ovaries.
The researchers intend to further examine U17 snoRNA to discover how it works with proteins, and hope that the results will also justify further research into how hormone-like chemicals in our environment might affect puberty and fertility, according to Prof Ory: “There are environmental cues that might be involved. We need to work with our colleagues in fertility research as we think about future directions for this work.”