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Female Infertility Linked with High Blood Cholesterol in Compelling Houston Methodist Trial

April 26, 2024 - Eden McCleskey

In an intriguing discovery, researchers at Houston Methodist Hospital have discovered a potential connection between infertility and blood cholesterol levels, offering hope for the millions of women facing difficulties conceiving.

Using a bacterial protein known as serum opacity factor, the research team successfully reversed infertility in sterile preclinical models by reducing elevated circulating cholesterol levels.

"Our findings provide compelling evidence linking high cholesterol to female infertility," said Corina Rosales, PhD, a professor of molecular biology at Houston Methodist Hospital. "Serum opacity factor, with its unique ability to alter the structure of cholesterol-carrying high-density lipoproteins (HDL), emerged as a potent tool in our research."

The study, published in the Journal of Lipid Research, is among the first to demonstrate that improving cholesterol levels can positively impact female fertility rates. It highlights serum opacity factor's remarkable effectiveness — the bacterial protein lowered cholesterol levels by more than 40% in just three hours.

The research team's focus on HDL, often referred to as good cholesterol, stems from the lipoprotein's crucial role in lipid metabolism.

To investigate HDL dysfunction, the team worked with mice genetically modified to lack receptors for HDL, resulting in unnaturally high levels of HDL cholesterol and sterility. When administered a lipid-lowering drug, the mice temporarily regained fertility, prompting further exploration into serum opacity factor's potential.

"Serum opacity factor's selectivity for HDL presented an intriguing opportunity," noted Dr. Rosales.

By delivering the gene for serum opacity factor to mice lacking HDL receptors, the researchers observed significant reductions in HDL cholesterol levels and permanent restoration of fertility.

The mechanism behind this restoration involves a series of biochemical reactions triggered by serum opacity factor binding to HDL molecules. This process ultimately leads to the clearance of lipid-rich HDL molecules, reducing cholesterol levels and restoring fertility.

Encouraged by their preclinical results, the researchers plan to conduct clinical studies to assess lipid levels in women with idiopathic infertility. If high HDL levels are identified, serum opacity factor may offer a potential treatment avenue.

"Even a small impact on infertility could be life-changing for those struggling to conceive," remarked Dr. Rosales, underscoring the significance of their research.

To learn more about the science behind the study and its potential impact on fertility and cholesterol research, click here to read an article in our sister publication, Methodology, or here to read the write-up in Science Direct.

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