Male microchimerism in women without sons: Quantitative assessment and correlation with pregnancy history

Yan, Zhen; Lambert, Nathalie C.; Guthrie, Katherine A.; Porter, Allison J.; Loubiere, Laurence S.; Madeleine, Margaret M.; Stevens, Anne M.; Hermes, Heidi M.; Nelson, J. Lee

doi:10.1016/j.amjmed.2005.03.037

« Previous Next »The American Journal of Medicine
Volume 118, Issue 8 , Pages 899-906, August 2005

Male microchimerism in women without sons: Quantitative assessment and correlation with pregnancy history

Zhen Yan, MD, PhD
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
- Requests for reprints should be addressed to Zhen Yan, MD, PhD, Immunogenetics D2-100, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, P.O. Box 19024, Seattle, WA 98109.
Nathalie C. Lambert, PhD
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
- Laboratoire d’ Immuno-rhumatologie, INSERM U639, Marseille, France.
Katherine A. Guthrie, PhD
- Clinical Statistics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
Allison J. Porter, BA
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
Laurence S. Loubiere, PhD
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
Margaret M. Madeleine, PhD
- Program in Cancer Epidemiology Research Cooperative, Fred Hutchinson Cancer Research Center, Seattle, Wash.
Anne M. Stevens, MD, PhD
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
- Department of Pediatrics, University of Washington, Seattle, Wash.
Heidi M. Hermes, BS
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
- Department of Pediatrics, University of Washington, Seattle, Wash.
J. Lee Nelson, MD
- Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash.
- Department of Medicine, Rheumatology, University of Washington, Seattle, Wash.

Received 7 December 2004; received in revised form 25 March 2005; accepted 25 March 2005.

Abstract

Purpose

Fetal microchimerism, derived from fetal cells that persist after pregnancy, is usually evaluated by tests for male microchimerism in women who gave birth to sons. We investigated male microchimerism in women without sons and examined correlation with prior pregnancy history. Immunologic consequences of microchimerism are unknown. We studied healthy women and women with rheumatoid arthritis (RA).

Methods

Y-chromosome-specific real-time quantitative polymerase chain reaction was used to test peripheral blood mononuclear cells of 120 women (49 healthy and 71 with RA). Results were expressed as the number of male cells that would be equivalent to the total amount of male DNA detected within a sample containing the equivalent of 100000 female cells.

Results

Male microchimerism was found in 21% of women overall. Healthy women and women with RA did not significantly differ (24% vs 18%). Results ranged from the DNA equivalent of 0 to 20.7 male cells per 100000 female cells. Women were categorized into 4 groups according to pregnancy history. Group A had only daughters (n = 26), Group B had spontaneous abortions (n = 23), Group C had induced abortions (n = 23), and Group D were nulligravid (n = 48). Male microchimerism prevalence was significantly greater in Group C than other groups (8%, 22%, 57%, 10%, respectively). Levels were also significantly higher in the induced abortion group.

Conclusions

Male microchimerism was not infrequent in women without sons. Besides known pregnancies, other possible sources of male microchimerism include unrecognized spontaneous abortion, vanished male twin, an older brother transferred by the maternal circulation, or sexual intercourse. Male microchimerism was significantly more frequent and levels were higher in women with induced abortion than in women with other pregnancy histories. Further studies are needed to determine specific origins of male microchimerism in women.

Keywords: Microchimerism , Pregnancy , Y chromosome