HOUSTON — High levels of cholesterol could be making women infertile, according to a new study from Houston.
Researchers discovered that high levels of “good” high-density lipoprotein (HDL) cholesterol could contribute to preventing conception.
Using a potent bacterial protein that can lower cholesterol levels by 40 percent in just three hours, scientists reversed infertility in sterile mice by reducing their levels of HDL cholesterol.
HDL is “good” because it carries excess cholesterol from different tissues to the liver for breakdown, thereby bringing down 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 as well as infertility.
By introducing this protein, serum opacity factor, it altered the structure of cholesterol-carrying HDLs, making it easier for the liver to dispose of the excess cholesterol that’s preventing conception.
The American researchers also noted that serum opacity factor’s dramatic action on HDL could be used as a potential alternative to statins, which are the current gold standard for lowering cholesterol in people with atherosclerosis.
Lead author Dr. Corina Rosales, assistant research professor of molecular biology in medicine with the Houston Methodist Research Institute, said: “We are working with a protein, called serum opacity factor, with unique characteristics.
“In our experiments, serum opacity factor lowered cholesterol levels by over 40 percent in three hours. So, this protein is quite poten,” she saidCholesterol is the backbone of all steroidal hormones, and an orchestra of hormones is needed to have a fertile animal.
“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.”
One in every five women of childbearing age in the U.S. may be unable to get pregnant after trying for a year.
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 furred arteries, Rosales observed that these mice were also completely sterile.
As predicted, when the researchers fed the sterile mice with a lipid-lowering drug, both LDL and HDL cholesterol levels were reduced and 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.
Dr. Rosales said: “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.
“We hypothesized that perhaps administering serum opacity factor to these mice might help restore their fertility, as well.”
Corresponding author Dr. Henry Pownall, of the Houston Methodist Research Institute, added: “Both HDLs and LDLs contain a mixture of free and esterified cholesterol, and free cholesterol is known to be toxic to many tissues.
“So, any dysfunction in HDL could be a risk factor for several diseases, too.”
Based on these promising preclinical results, the researchers next plan to conduct a clinical study to investigate lipid levels in women undergoing treatments for 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.
Dr. Rosales said: “Even if we were to help one percent 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.”
The study was published in the American Society for Biochemistry and Molecular Biology’s Journal of Lipid Research.
Produced in association with SWNS Talker
Edited by Jessi Rexroad Shull and Kyana Jeanin Rubinfeld