A lack of a particular type of immune system cell could explain why some women are infertile, suggest Australian researchers.The immune cells, known as macrophages, create a healthy hormone environment in the uterus, report Dr Sarah Robertson and colleagues today online in the Journal of Clinical Investigations.
“About 50 per cent of couples can’t have their infertility attributed to any particular cause,” says Robertson, a professor of reproductive medicine at Adelaide University.”This could be one of the causes why people end up needing IVF.”Macrophages, which are well known for their function as immune cells, are in large numbers in the uterus and ovary at conception.
To test what role the macrophages were playing in reproduction, Robertson and colleagues used transgenic mice that can have their macrophages temporarily eliminated.They originally thought macrophages would protect these tissues from infection or play a role in immune adaptation to ensure the female body doesn’t reject the embryo that contains male genetic material.
But while they discovered the mice were infertile when the macrophages were eliminated, there was no evidence this was due to immune dysfunction.”What we found was a hormonal dysfunction,” says Robertson. “We found progesterone, which is a critical hormone for pregnancy, was very much abnormal in these mice.”Progesterone is produced by a part of the ovary called the corpus luteum, and is absolutely essential in making the uterus receptive to implantation by the fertilised egg.”Without progesterone you cannot have implantation,” says Robertson. “It’s a limiting factor in whether or not pregnancy can occur.”
She and colleagues found that when macrophages were eliminated, the corpus luteum was abnormal, and implantation could not occur.”It was disorganised and haemorrhagic — full of blood,” says Robertson.The researchers found that when the mice were injected with progesterone or macrophages the fertilised egg could implant once again.
“We completely rescued the infertility defect,” says Robertson. “That showed us that all of the infertility was completely attributable to the faulty corpus luteum and the consequent reduction of progesterone.”
Robertson says she and colleagues found a particular subset of macrophages, called M2 macrophages, play a role in building up a network of blood vessels in the corpus luteum so it rapidly grows in size and produces the progesterone needed for reproduction.
She says this tissue-remodelling role of macrophages has been seen before in foetuses and in tumours, but this is the first time it has been seen in the normal adult body — in the corpus luteum.Robertson says this is not surprising given the corpus luteum’s unique function.
“When you think about it there isn’t anywhere else in the body where you have to develop a tissue from scratch in such a short period of time and get a blood supply in so fast,” she says.Women who are having difficulty conceiving are treated using progesterone supplements, and the new findings this may help explain why these women are deficient in progesterone in the first place.And, says Robertson, the findings may lead to less interventionist treatments based on modifying lifestyle and diet, which are known to influence macrophage levels.
“We’re keen to understand what’s at the root of the infertility,” she says.
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