Microchimerism: What is the impact on women's health and pregnancy?

Posted By Braverman IVF & Reproductive Immunology || 30-Oct-2015

What is microchimerism?

Microchimerism is the presence of cells that originated in a genetically different individual. This event can occur through:

  • Feto-maternal microchimerism: a bidirectional process during pregnancy where some cells traffic from the mother to the fetus and from the fetus to the mother (fetal DNA, small fragment of placenta)
  • A vanishing twin
  • Blood transfusion

It has only recently become known to the public through the media, that naturally-acquired microchimerism is common in humans and has a real impact on health although there has been quite a bit about it published in the medical literature over the past 25 years.

Microchimerism has been recently put into the spotlight with this incredible story of the first human chimera (with at least 2 genetically distinct types of cells) whose unborn vanishing twin fathered his own child.

This 34 years old American man had a son through an IVF procedure and found out after a paternity test (run to rule out a possible mistake during the IVF cycle as his child had a blood type incompatible with the one the couple had) that his son was not his.
Because the IVF clinic maintained that no mistakes were made, the couple underwent a genetic ancestry test to finally find out that their son’s father was the man’s own twin brother, who had never been born.

How this can be possible?

This man inherit his brother’s genome in their mother’s womb. The two embryos fused and as a result, some of his organs will have the genome A (his brother’s) while others will have the genome B (his own genome).

Microchimerism and recurrent pregnancy losses

Maternal–paternal immunogenetic relationships influence pregnancy outcomes. Disparity in human leukocyte antigen (HLA) genes between the mother and the father has a beneficial effect on pregnancy success while a lack of disparity in the class II HLA genes between the parents can be detrimental to a successful pregnancy.
Microchimerism occurs between the mother and the fetus she is carrying while pregnant. A women also acquires microchimerism from her own mother when she herself was a fetus (MP microchimerism) leading to a multi-generational process.
A recent study showed that women with recurrent pregnancy loss have a lower level of MP microchimerism compared to women with no history of losses (1). Interestingly a lack of MP microchimerism was also noted in pregnancy complication such as pre-eclampsia (2).
Another study showed that maternal cells transferred to the fetus while in utero, influence the development of fetal regulatory T cells to non-inherited maternal HLA antigens which play a key role in feto-maternal tolerance (3) and pregnancy maintenance. This has a long-lasting impact on maternal health and transplant outcomes later in life (4).
MP microchimerism shapes and promotes systemic accumulation of immune suppressive regulatory T cells in a cross- generational way to increase reproductive potential (5) in other words the mother to be had a life-long training of her immune tolerance towards the future embryo, thanks to the MP microchimerism coming from her own mother.

It is not yet determined if fetal microchimerism from a prior pregnancy impacts subsequent pregnancies in women with recurrent pregnancy losses.

Fetal microchimerism: Yin-Yang effects on maternal health

Fetal cells are largely found in the maternal circulation during pregnancy and persist in the circulation of women many years after childbirth.

  1. Fetal cells microchimerism: improvement of symptoms in several autoimmune conditions

In pregnant patients affected by rheumatoid arthritis (RA) or multiple sclerosis (MS), symptoms of the disease have been reported to significantly improve during pregnancy. Maternal immune adaptation to a pregnancy involved specific cells (Treg cells) that induce tolerance to fetal antigen (exposed to the maternal immune system by fetal microchimerism) and subsequently prevent some autoimmune diseases.
The amelioration in symptoms of several autoimmune diseases during pregnancy has been shown to be regulated by the extent of feto-maternal HLA class II disparity, with greater allelic disparity inducing greater remission (6). This is a collateral effect of the maternal immune adaptation to the fetus. This same adaptation is what also leads to pregnancy success while failure to adapt leads to recurrent pregnancy loss.

  1. Fetal cells microchimerism: aggravation of symptoms in some autoimmune diseases

Fetal microchimerism has also been associated with flare of scleroderma and thyroiditis during pregnancy (7-8).
It has been found that the presence of fetal DNA is much more important in pregnant patients with scleroderma than the fetal DNA found in most normal pregnant women (9). HLA class II compatibility between a child and his mother was more common among scleroderma patients than among controls. Therefore, fetal microchimerism and a lack of feto-maternal class II disparity could trigger the disease.

  1. Beneficial role of fetal microchimerism in cancer?

Several studies have supported a protective role of fetal microchimerism against breast cancer. Supporting these facts, male DNA (fetal microchimerism), was less prevalent in peripheral blood of women with breast cancer than healthy women (10-11) although it is highly dependent of the type of breast cancer.
Similar to observations in breast cancer, women with papillary thyroid cancer have a lower prevalence of male DNA compared to healthy women (12).

We have been taught that each individual is genetically unique (at the exception of identical twin) and contain a single genetic code. In fact, it is a little more complicated as we are, in some of our cells, a partial genetic mosaic of our family (maternal and fetal microchimerism through our mother, children but also older siblings).
Maternal immune response to fetal cells plays a key role in maternal health, pregnancy outcome or diseases, and fetal microchimerism could be a key factor in all of these processes.


  1. Gammill HS, Stephenson MD, Aydelotte TM, Nelson JL. Microchimerism in women with recurrent miscarriage. Chimerism. 2015 Mar 16:1-3.
  2. Mold JE, Michaelsson J, Burt TD, Muench MO, Beckerman KP, Busch MP et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 2008; 322: 1562–1565.
  3. Gammill HS, Adams Waldorf KM, Aydelotte TM, Lucas J, Leisenring WM, Lambert NC et al. Pregnancy, microchimerism, and the maternal grandmother. PLoS One 2011; 6: e24101.
  4. Burlingham W, Grailer A, Heisey D, Claas F, Norman D, Mohanakumar T et al. The Effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. N Engl J Med 1998; 339: 1657–1664.
  5. Kinder JM, Jiang TT, Ertelt JM, Xin L, Strong BS, Shaaban AF, Way SS. Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells. Cell. 2015 Jul 30; 162(3):505-15.
  6. Nelson JL, Hughes KA, Smith AG, Nisperos BB, Branchaud AM, Hansen JA. Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med. 1993 Aug 12; 329(7):466-71.
  7. Artlett, C.M., Smith, J.B. & Jimenez, S.A. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N. Engl. J. Med. 338, 1186–1191 (1998).
  8. Klintschar, M., Schwaiger, P., Mannweiler, S., Regauer, S. & Kleiber, M. Evidence of fetal microchimerism in Hashimoto’s thyroiditis. J. Clin. Endocrinol. Metab. 86, 2494–2498 (2001).
  9. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, Bean MA, Ober C, Bianchi DW. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet. 1998 Feb 21; 351(9102):559-62.
  10. Gadi VK, Nelson JL. 2007. Fetal microchimerism in women with breast cancer. Cancer Res. 67: 9035–8. 55.
  11. Gadi VK, Malone KE, Guthrie KA, Porter PL, et al. 2008. Case-control study of fetal microchimerism and breast cancer. PLoS One 3: e1706.
  12. Cirello V, Perrino M, Colombo C, Muzza M, Filopanti M, Vicentini L, Beck-Peccoz P, Fugazzola L. Fetal cell microchimerism in papillary thyroid cancer: studies in peripheral blood and tissues. Int J Cancer. 2010 Jun 15; 126(12):2874-8.
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