News | Bacterial Protein Lowers Cholesterol and Reverses Infertility in Mice
Houston Methodist scientists used a bacterial protein called serum opacity factor to lower high cholesterol and reverse infertility in mice. The study adds evidence linking high cholesterol with female infertility and suggests a possible new treatment direction. Houston Methodist notes that one in five U.S. women of reproductive age do not conceive after one year of trying.
“We are studying a protein with unique properties called serum opacity factor,” said lead author Corina Rosales, PhD, assistant professor of molecular biology at the Houston Methodist Research Institute. “In our experiments, it reduced cholesterol by more than 40% in just three hours. It is a very potent protein.” The findings were published in the Journal of Lipid Research.
Serum Opacity Factor: A Cholesterol-Lowering Bacterial Protein
Serum opacity factor primarily helps bacteria colonize, but it can also alter cholesterol-carrying high-density lipoprotein (HDL), helping the liver remove excess cholesterol that may hinder pregnancy. Its strong effect on HDL may offer an alternative to statins used to lower cholesterol in patients with atherosclerosis.
HDL, often called “good cholesterol,” carries excess cholesterol from tissues to the liver for breakdown. If HDL malfunctions, lipid metabolism changes and may produce harmful effects similar to low-density lipoprotein (LDL), or “bad cholesterol.” LDL carries cholesterol from the liver to other tissues, and excessive levels can cause buildup and disease.
“HDL and LDL both contain free and esterified cholesterol. Free cholesterol is toxic to many tissues, so dysfunctional HDL may be a risk factor for several diseases,” said Henry J. Pownall, PhD, professor of biochemistry at Houston Methodist Research Institute.
High HDL Cholesterol and Infertility
The team used a preclinical mouse model with abnormally high HDL cholesterol. Although ideal for studying atherosclerosis, the mice were also completely infertile.
“Cholesterol is the basis of all steroid hormones, and successful reproduction requires coordinated hormones,” Dr. Rosales explained. “HDL receptors are present throughout the ovaries, so HDL metabolism must play a vital role in fertility.”
Serum Opacity Factor Reverses Infertility
A lipid-lowering drug reduced both LDL and HDL cholesterol in the mice and temporarily restored fertility. Researchers then tested serum opacity factor, which binds mainly to HDL rather than LDL or other lipoproteins.
“Serum opacity factor was first recognized as a virulence factor in streptococcal infections, but was later found to react almost exclusively with HDL,” Dr. Rosales said. “We hypothesized that it might restore fertility in these mice.”
The team used an adeno-associated virus to deliver the serum opacity factor gene to mice lacking HDL receptors and having high blood cholesterol. Once the gene was expressed, HDL cholesterol fell significantly and fertility returned.
Next Step: Human Clinical Research
Based on these promising preclinical results, researchers plan to study lipid levels in women receiving treatment for unexplained infertility. If HDL cholesterol is high, serum opacity factor may offer a future treatment direction.
“Even if we help only 1% of women trying to conceive, it could change their lives. That is where our research may have the greatest impact,” Dr. Rosales concluded.
Research Team and Funding
The study was conducted by Corina Rosales, Henry J. Pownall, Dedipya Yelamanchili, Baiba K. Gillard, Jing Liu, and colleagues at Houston Methodist Research Institute. It was funded by the National Institutes of Health (NIH) and the Bass Foundation.
News | Bacterial Protein Lowers Cholesterol and Reverses Infertility in Mice
News | Bacterial Protein Lowers Cholesterol and Reverses Infertility in Mice
Houston Methodist scientists used a bacterial protein called serum opacity factor to lower high cholesterol and reverse infertility in mice. The study adds evidence linking high cholesterol with female infertility and suggests a possible new treatment direction. Houston Methodist notes that one in five U.S. women of reproductive age do not conceive after one year of trying.
“We are studying a protein with unique properties called serum opacity factor,” said lead author Corina Rosales, PhD, assistant professor of molecular biology at the Houston Methodist Research Institute. “In our experiments, it reduced cholesterol by more than 40% in just three hours. It is a very potent protein.” The findings were published in the Journal of Lipid Research.
Serum Opacity Factor: A Cholesterol-Lowering Bacterial Protein
Serum opacity factor primarily helps bacteria colonize, but it can also alter cholesterol-carrying high-density lipoprotein (HDL), helping the liver remove excess cholesterol that may hinder pregnancy. Its strong effect on HDL may offer an alternative to statins used to lower cholesterol in patients with atherosclerosis.
HDL, often called “good cholesterol,” carries excess cholesterol from tissues to the liver for breakdown. If HDL malfunctions, lipid metabolism changes and may produce harmful effects similar to low-density lipoprotein (LDL), or “bad cholesterol.” LDL carries cholesterol from the liver to other tissues, and excessive levels can cause buildup and disease.
“HDL and LDL both contain free and esterified cholesterol. Free cholesterol is toxic to many tissues, so dysfunctional HDL may be a risk factor for several diseases,” said Henry J. Pownall, PhD, professor of biochemistry at Houston Methodist Research Institute.
High HDL Cholesterol and Infertility
The team used a preclinical mouse model with abnormally high HDL cholesterol. Although ideal for studying atherosclerosis, the mice were also completely infertile.
“Cholesterol is the basis of all steroid hormones, and successful reproduction requires coordinated hormones,” Dr. Rosales explained. “HDL receptors are present throughout the ovaries, so HDL metabolism must play a vital role in fertility.”
Serum Opacity Factor Reverses Infertility
A lipid-lowering drug reduced both LDL and HDL cholesterol in the mice and temporarily restored fertility. Researchers then tested serum opacity factor, which binds mainly to HDL rather than LDL or other lipoproteins.
“Serum opacity factor was first recognized as a virulence factor in streptococcal infections, but was later found to react almost exclusively with HDL,” Dr. Rosales said. “We hypothesized that it might restore fertility in these mice.”
The team used an adeno-associated virus to deliver the serum opacity factor gene to mice lacking HDL receptors and having high blood cholesterol. Once the gene was expressed, HDL cholesterol fell significantly and fertility returned.
Next Step: Human Clinical Research
Based on these promising preclinical results, researchers plan to study lipid levels in women receiving treatment for unexplained infertility. If HDL cholesterol is high, serum opacity factor may offer a future treatment direction.
“Even if we help only 1% of women trying to conceive, it could change their lives. That is where our research may have the greatest impact,” Dr. Rosales concluded.
Research Team and Funding
The study was conducted by Corina Rosales, Henry J. Pownall, Dedipya Yelamanchili, Baiba K. Gillard, Jing Liu, and colleagues at Houston Methodist Research Institute. It was funded by the National Institutes of Health (NIH) and the Bass Foundation.
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