Could decreasing HDL cholesterol be a potential treatment method for female infertility?

There are two types of cholesterol: high density (HDL) and low density (LDL). LDL cholesterol is considered “bad cholesterol” because it can promote the formation of plaques and fatty deposits on the walls of arteries in the heart when present in excessive amounts. As for HDL, it eliminates the excess cholesterol found in the body. It is therefore the “good cholesterol”.

In particular, HDL transports excess cholesterol from different tissues to the liver to be broken down there in order to reduce the total cholesterol level. However, in the event of HDL dysfunction, lipid metabolism is impaired, which can then be harmful to the body.

Lowering HDL Cholesterol Could Reverse Infertility

Any HDL dysfunction could therefore be a risk factor for different diseases. For researchers at Houston Methodist Hospital (USA), there is a link between hypercholesterolemia, a metabolic disorder linked to an increase in cholesterol levels in the blood, and infertility.

During this research, the scientists notably succeeded in reversing the sterility of infertile mice by reducing circulating HDL cholesterol thanks to a bacterial protein. “We are working with a protein, called serum opacity factor, which has unique characteristics (…) In our experiments, serum opacity factor reduced cholesterol levels by more than 40% in three hours. This protein is therefore very powerful. said Corina Rosales, lead author of the study, MD and assistant professor of molecular biology at the Houston Methodist Research Institute. The results of this work have been published in the Journal of Lipid Research de l’American Society for Biochemistry and Molecular Biology.

“HDL metabolism therefore had to play a very important role in fertility”

First, the researchers observed infertile mice that showed abnormally high levels of HDL cholesterol in their bloodstream. “Cholesterol is the backbone of all steroid hormones, and an orchestra of hormones is needed to achieve a fertile animal (…). We know that the ovaries are studded with receptors for HDL, so HDL metabolism had to play a very important role in fertility for this reason” said the specialist.

During the research, the scientists fed the sterile mice a lipid-lowering drug. LDL as well as HDL cholesterol levels then decreased and the subjects were temporarily saved from infertility. Faced with these encouraging results, they decided to carry out tests on rodents with the serum opacity factor.

“Serum opacity factor is best known in the context of bacterial streptococcal infections, where it serves as a virulence factor. But it has also been found that this protein only responds to HDL, not LDL or other other lipoproteins”, explained Corina Rosale. The researchers therefore speculated that perhaps administering a serum opacity factor to these mice could help restore their fertility.

A clinical study to assess the serum opacity factor in infertile women

The team then developed an adeno-associated virus to deliver the serum opacity factor gene to mice that lack HDL receptors and have high blood cholesterol levels. HDL cholesterol was significantly lowered and fertility was restored when the gene has been expressed and the bacterial protein has been produced.

Within the next few months, researchers want to begin a clinical study to examine lipid levels in women undergoing treatment for idiopathic infertility, i.e. whose underlying causes are not not fully known. For the American team, the serum opacity factor could be a possible treatment if these patients present with high levels of HDL.