Have Scientists Discovered a Way to Reverse Infertility

A recent animal study suggests that infertility can be reversed in sterile mice by reducing high-circulating cholesterol

Highlights:

Infertility affects millions of people of reproductive age worldwide – and has an impact on their families and communities
A recent study shows that infertility can be reversed by lowering HDL cholesterol
This can be achieved by a bacterial protein that can reduce levels of cholesterol by over 40% in three hours

Motherhood is often considered a beautiful aspect of a woman’s life. Infertility affects millions of people worldwide. One in every five women of childbearing age is unable to get pregnant after a year. Very often, this can be disheartening and upsetting.

However, there is hope for those women who are suffering from infertility. By lowering high levels of circulating cholesterol with a bacterial protein, researchers at Houston Methodist demonstrated yet another link between high cholesterol and female infertility in sterile mice. This could be a revolutionary development.

"We are working with a protein, called serum opacity factor, with unique characteristics," said Corina Rosales, Ph.D., assistant research professor of molecular biology in medicine with the Houston Methodist Research Institute and lead author on the study. "In our experiments, the serum opacity factor lowered cholesterol levels by over 40% in three hours. So, this protein is quite potent."

The results were published in the Journal of Lipid Research.

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‘Scientists have now discovered a way to reverse infertility: by reducing HDL cholesterol’

Role of Bacterial Protein in Reducing Cholesterol

Even though this protein's main objective is to promote bacterial colonization, it also changes the structure of HDLs, or high-density lipoproteins, which helps the liver get rid of the extra cholesterol that prevents conception.

The authors also observed that the serum opacity factor's dramatic action on HDL could be used as a potential alternative to statins, which are currently the gold standard for lowering cholesterol in people with atherosclerosis.

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Good vs Bad Cholesterol

The ‘good cholesterol,’ or HDL, transports extra cholesterol from various tissues to the liver for breakdown, lowering blood cholesterol levels. However, if there is HDL dysfunction, lipid metabolism gets altered, which could then be harmful, like its counterpart LDL, or low-density lipoprotein. Often called ‘bad cholesterol’, LDL carries cholesterol from the liver to other tissues, with high levels of it causing accumulation and diseases.

"Both HDLs and LDLs contain a mixture of free and esterified cholesterol, and free cholesterol is known to be toxic to many tissues," said Henry J. Pownall, Ph.D., professor of biochemistry in medicine at the Houston Methodist Research Institute and corresponding author on the study. "So, any dysfunction in HDL could be a risk factor for several diseases, too."

To study HDL dysfunction, the researchers worked with preclinical mouse models that had unnaturally high levels of HDL cholesterol circulating in their bloodstream. While this made them ideal for studying atherosclerosis, Rosales observed that these mice were also completely sterile.

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Cholesterol and Infertility

"Cholesterol is the backbone of all steroidal hormones, and an orchestra of hormones is needed to have a fertile animal," Rosales said. "We know that the ovaries are studded with receptors for HDL, so the metabolism of HDL had to play a very important role in fertility for that reason."

As expected, when the authors fed the sterile mice with a lipid-lowering drug, both LDL and HDL cholesterol levels were reduced. Thereby, the animals were temporarily rescued from infertility. Motivated by these results, they turned to the bacterial protein serum opacity factor, known to be highly selective for HDL.

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Serum Opacity Factor, Cholesterol, and Fertility

"Serum opacity factor is known mainly in the context of bacterial strep infections where it serves as a virulence factor. But it was also discovered that this protein only reacts to HDL and not to LDL or other lipoproteins," Rosales said. "We hypothesized that perhaps administering serum opacity factor to these mice might help restore their fertility, as well."

For their second round of tests, the scientists developed an adeno-associated virus to deliver the gene for serum opacity factor to the mice lacking HDL receptors that had high blood cholesterol. When the gene was expressed and the bacterial protein was produced, the animals' HDL cholesterol significantly lowered, and their fertility was restored.

On the basis of these promising preclinical results, the researcher’s next plan to conduct a clinical study to investigate lipid levels in women undergoing treatments for idiopathic infertility, where the underlying causes are not fully known. If these patients have high HDL levels, then the researchers say serum opacity factor may be a line of future treatment.

"Even if we were to help 1% of women who are struggling to conceive, it would be life-changing for them, and I think that's where we can make the most impact with our research," Rosales said.

Reference:

Serum opacity factor rescues fertility among female Scarb1−/− mice by reducing HDL-free cholesterol bioavailability - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932678/)

Source-Medindia