Tracy was waiting for the right time to get pregnant, but when she was finally ready, she couldn’t get pregnant. She underwent many tests and expensive procedures, including in vitro fertilization, but all efforts failed. Endocrinologist Annabelle Rodriguez at John Hopklns University in Baltimore thinks that a genetic cholesterol-related gene may cause infertility in a portion of infertile women. Cholesterol, in excess, causes arterial plaques and heart disease, but it is an important and necessary constituent of all tissues in the human body.
Cholesterol not all bad
Cholesterol is important for life; it is needed to build and repair all animal and human cell membranes and to make bile acids and steroid hormones, such as estrogen, progesterone, and testosterone. Cholesterol travels in the blood stream combined with proteins, forming particles, which include LDL (Low Density Lipoprotein) and HDL (High Density Lipoprotein). LDL particles deliver cholesterol to various tissues in the body. It is considered the bad cholesterol, but studies show that higher LDL levels promote muscle building. The HDL particle, the good cholesterol, picks up excess cholesterol from cells, including the cells that line blood vessels, and delivers it to the liver, adrenals, and ovaries. The delivered cholesterol is transferred from the liver to the intestine and eliminated, while the cholesterol delivered via HDL to the adrenals and ovaries is used to make steroid hormones.
Lack of cholesterol causes infertility
The method by which HDL delivers cholesterol to cells is via a cell membrane protein, called SR-B1 (Scavenger Receptor class B, type 1). Monty Krieger at the Massachusetts Institute of Technology in Cambridge created mice that lack the SR-B1 receptor. Because HDL could not clear cholesterol from the blood and deliver it, cholesterol build up in the bloodstream of these mice and caused severe heart disease, even though the mice had high levels of good HDL. An unexpected side effect of this experiment was that all female mice were infertile.
Infertility associated with cholesterol-related gene
Annabelle Rodriguez at John Hopkins thought that infertility in humans may also be caused by HDL-cholesterol’s failure to enter cells. She found that people with low SR-B1 protein, the HDL receptor, have higher HDL blood levels and lower levels of progesterone hormone, which is critical for maintaining a pregnancy. When she looked at women undergoing in vitro fertilization treatment, she found that about 15 percent of women had an abnormal SR-B1 gene and a low progesterone level. None of these women were able to become pregnant after transfer of an embryo, while 30 percent of the women with a normal SR-B1 gene became pregnant.
Considerations
In the mouse experiment, a drug that lowered LDL and HDL could reverse infertility. The drug probucol, used in the experiment, cannot be used in humans; it was removed from the market because of serious side effects. But Rodriguez believes that because a drug could reverse infertility, other drugs with fewer or no side effects can be developed. Researchers have also developed a blood test to detect the abnormal SR-B1 gene.
Sources
Couzin-Frankel, J. Mice prompt look at cholesterol’s role in female fertility. Science (2011) 332, 1252
Yates, M. et al. Clinical impact of scavenger receptor class B type 1 gene polymorphisms on human female fertility. Human Reproduction (2011) 26, 1910
http://www.sciencedaily.com/releases/2011/05/110505142730.htm
http://www.sciencedaily.com/releases/2011/05/110516121541.htm