June 5, 2003 -- Stress has long been suspected as a possible cause of miscarriage, with several studies indicating an increased risk among women reporting high levels of emotional or physical turmoil in their early months of pregnancy or just before conception. But while a relationship has been noted, researchers didn't know exactly how a woman's stress could cause miscarriage.
In what may prove to be a breakthrough finding, a team of scientists from Tufts University and Greece have identified a suspected chain reaction detailing exactly how stress hormones and other chemicals wreak havoc on the uterus and fetus. Their report, in the June issue of Endocrinology, may help explain why women miscarry for no obvious medical reasons and why some women have repeated miscarriages. And it could lead to measures to prevent miscarriage -- medically known as "spontaneous abortion."
Researchers have long known that during times of stress, the brain releases several hormones -- including one called corticotropin-releasing hormone (CRH). In past research, women who deliver prematurely or have low-birth-weight babies were often found to have high levels of CRH in their bloodstream, and other studies show a greater risk of miscarriage in women reporting stress. CRH is a hormone the brain secretes in reaction to physical or emotional stress, and it is also produced in the placenta and the uterus of a pregnant woman to trigger uterine contractions during delivery.
But this new research suggests that CRH and other stress hormones may also be released elsewhere in the body, where it specifically targets localized mast cells -- those best known for causing allergic reactions. Mast cells are abundant in the uterus. During stress, the local release of CRH causes these mast cells to secrete substances that can cause miscarriages.
The Hormone-Allergy Link
In their study of 23 women, the scientists found that those who had previous multiple miscarriages had significantly high levels of CRH and another hormone, urocortin, in the tissues of their fetuses when compared with women who miscarried once or those who had had abortions.
The lead researcher tells WebMD what's especially intriguing is that high amounts of these stress hormones were found only in uterine mast cells -- and not in the women's bloodstream, adding credence to his theory that CRH may be released locally.
"Mast cells are like a soccer ball that is filled with about 500 Ping-Pong balls, and each Ping-Pong ball has about 30 marbles," says Theoharis C. Theohardies, MD, PhD, of the Tufts University School of Medicine. "If you are allergic, these cells explode like a grenade to trigger an allergic reaction by releasing all those balls of histamine and various other chemicals."
Like an allergen, CRH and urocortin in mast cells may also release many chemicals. The chemicals known to cause fetal loss were also found in high amounts in the women studied who had one or more miscarriages.
"Tryptase [the chemical released by the activated mast cell] acts like a meat tenderizer, destroying tissue, and it prevents the production of membranes to develop the embryo and disrupts the whole architecture of the placenta that feeds the baby," Theohardies tells WebMD. "When this happens early in pregnancy, it causes a miscarriage."
"I think this is very exciting," says Calvin J. Hobel, MD, of Cedars-Sinai Medical Center in Los Angeles, whose study four years ago in the American Journal of Obstetrics and Gynecology linked high CRH levels with a greater risk of premature birth. "It brings the continuum together because most of us have been looking at [CRH's effect on] the end of pregnancy or the middle of pregnancy."
Hobel tells WebMD that Theohardies' finding could play a key role in the future of prenatal diagnosis, in which a piece of the placenta is removed and cells are examined for genetic disorders. He is researching how CRH can be studied this way to better ensure a full-term and healthy delivery.
And Theohardies says he is hopeful that with his new research, women at risk of miscarriage may be able to take preventative measures, especially when under stress during pregnancy. "We know how to block the action of CRH on mast cells, so perhaps we could give women at risk a vaginal suppository with drugs that block CRH receptors."
But more immediately, he says his finding offers more proof of the hazards of emotional stress on pregnancy. "We now know the effects of stress (on the fetus) are very real and produce a specific physiologic reaction in the uterus," he tells WebMD. "So you really need to reduce it whatever way you can."