Healthy mother, healthy child
The normal role of white blood cells is to battle infection throughout the body – but that’s not their only function. Dr. Anne Croy, a reproductive immunologist in the Faculty of Health Sciences, is studying a particular type of white blood cell, or leucocyte, that floods into the uterus early in pregnancy to play a critical role in enlarging the blood vessels that carry nutrients from the mother to the developing placenta, a jelly-like sac that supports the growing fetus. If these arteries are narrower than they should be, the blood flow is restricted, which harms both mother and baby.
The white blood cells Croy studies – forebodingly called Natural Killer lymphocytes – are an intriguing puzzle. Normally they make up about one per cent of normal human blood. In stark contrast, they comprise 75% of the blood at the embryo implant site early in pregnancy or during a woman’s menstrual cycle when the uterus prepares for a potential pregnancy.
This discrepancy is no accident. “It’s not like these cells are just passing through and want to say hello,” says Croy. “This is a specific functional recruitment of significance.”
As they do in humans and other mammals, the white blood cells moving into the uterus cause the arteries at the embryo implant site – known as the maternal-fetal interface – to dilate and lose their smooth muscle coating. This enables up to 500 times more blood to flow through the modified arteries than is the case in a “virgin” uterus. The higher blood flow is critical.
“The last thing a developing fetus wants is an interruption to its blood supply,” says Croy. “The fetus doesn’t have functional lungs and its heart doesn’t work until later in pregnancy, so continuation of pregnancy after implantation depends completely on the mother’s blood to exchange nutrition, oxygen and glucose with the fetus, and for waste excretion.”
"It's not like these cells are just passing through and want to say hello," says Croy. "This is a specific functional recruitment of significance."
One potential complication stemming from below-normal blood flow to the human placenta is a syndrome called preeclampsia, which is characterized by high blood pressure in the mother, possibly leading to kidney failure and necessitating premature delivery of the baby. Although the child may be born healthy, studies show that long-term consequences of preeclampsia to the mother can include cardiovascular disease and stroke. Another syndrome of reduced blood flow to the placenta, intrauterine growth retardation, causes babies to be born at term, but dramatically underweight.
Croy examines the maternal-fetal interface using specially bred, immune-deficient mice. She rebuilds components of their immune systems with genetically altered cells, which enables her to study the impact of the gene changes on the functions of the Natural Killer cells in a normal pregnancy when the mice are mated. Croy monitors what happens using tiny radio transmitters surgically implanted into each mouse. These measure the mouse’s blood pressure and other properties of circulation continuously. She also uses a miniature mouse ultrasound machine to monitor the flow of blood in living mothers and fetuses. These are highly specialized techniques.
For the past 12 years, Croy has collaborated with Dr. Aureo Yamada, who studies the same subject at the University of Campinas in Sao Paulo State, Brazil. Both investigators hold awards from their respective federal trade and education branches to orchestrate a series of student exchanges that have sent Queen’s PhD students to Brazil and brought Brazilian PhD students to Queen’s. The purpose of the visits is to transfer knowledge about Natural Killer cell cultures
and pregnancy failure, which is Yamada’s expertise, and the use of radiotelemetry and ultrasound techniques in healthy mouse pregnancy, which is Croy’s expertise. Too, for the past seven years, Croy and her Queen’s colleagues who study pregnancy have organized the Human Placenta Summer Workshop, an in-depth, 60-hour course on the placenta that takes place at Queen’s.
The workshop serves as a platform for two-way communication of information between basic scientists like Croy and clinical scientists working with pregnant women. Since its inception, the workshop has disseminated knowledge about techniques for studying the human placenta to more than 100 trainees from 25 different countries.
The ultimate goal of Croy’s research is to develop approaches that can safely increase the blood flow to the human maternal-fetal interface when this is compromised (by, for instance, diabetes or high blood pressure). She already shares a patent for a biological agent that does this in pigs.
“A human immune therapy is a long way off, but that would be the Holy Grail,” says Croy. “The point of all of my research is to promote the health of human mothers and their babies.”
Profile by Alec Ross