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Published on: August 6, 2014
Male microchimerism in females: a quantitative study of twin pedigrees to investigate mechanisms
B N Johnson1,2, H E Peters3,4, C B Lambalk3,4
1Avera Institute for Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, SD, USA.
Study Question:
Does having a male co-twin, older brothers, or sons lead to an increased probability of persistent male microchimerism in female members of twin pedigrees?
Summary Answer:
The presence of a male co-twin did not increase risk of male microchimerism and the prevalence of male microchimerism was not explained by having male offspring or by having an older brother.
What Is Known Already:
Microchimerism describes the presence of cells within an organism that originate from another zygote and is commonly described as resulting from pregnancy in placental mammals. It is associated with diseases with a female predilection including autoimmune diseases and pregnancy-related complications. However, microchimerism also occurs in nulliparous women; signifying gaps in the understanding of risk factors contributing to persistent microchimerism and the origin of the minor cell population.
Study Design, Size, Duration:
This cross-sectional study composed of 446 adult female participants of the Netherlands Twin Register (NTR).
Participants/Materials, Setting, Methods:
Participants included in the study were female monozygotic (MZ) twins, female dizygotic same-sex twins and females of dizygotic opposite-sex twin pairs, along with the mothers and sisters of these twins. Peripheral blood samples collected from adult female participants underwent DNA extraction and were biobanked prior to the study. To detect the presence of male-origin microchimerism, DNA samples were tested for the relative quantity of male specific Y chromosome gene DYS14 compared to a common β-globin gene using a highly sensitive quantitative PCR assay.
Main Results And The Role Of Chance:
We observed a large number of women (26.9%) having detectable male microchimerism in their peripheral blood samples. The presence of a male co-twin did not increase risk of male microchimerism (odds ratio (OR) = 1.23: SE 0.40, P = 0.61) and the prevalence of male microchimerism was not explained by having male offspring (OR 0.90: SE 0.19, P = 0.63) or by having an older brother (OR = 1.46: SE 0.32, P = 0.09). The resemblance (correlation) for the presence of microchimerism was similar (P = 0.66) in MZ pairs (0.27; SE 0.37) and in first-degree relatives (0.091; SE 0.092). However, age had a positive relationship with the presence of male microchimerism (P = 0.02).
Limitations, Reasons For Caution:
After stratifying for variables of interest, some participant groups resulted in a low numbers of subjects. We investigated microchimerism in peripheral blood due to the proposed mechanism of cell acquisition via transplacental blood exchange; however, this does not represent global chimerism in the individual and microchimerism may localize to numerous other tissues.
Wider Implications Of The Findings:
Immune regulation during pregnancy is known to mitigate allosensitization and support tolerance to non-inherited antigens found on donor cells. While unable to identify a specific source that promotes microchimerism prevalence within pedigrees, this study points to the underlying complexities of natural microchimerism in the general population. These findings support previous studies which have identified the presence of male microchimerism among women with no history of pregnancy, suggesting alternative sources of microchimerism. The association of detectable male microchimerism with age is suggestive of additional factors including time, molecular characteristics and environment playing a critical role in the prevalence of persistent microchimerism. The present study necessitates investigation into the molecular underpinnings of natural chimerism to provide insight into women's health, transplant medicine and immunology.
Study Funding/Competing Interest(S):
This work is funded by Royal Netherlands Academy of Science Professor Award (PAH/6635 to D.I.B.); The Netherlands Organisation for Health Research and Development (ZonMw)-Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw 911-09-032); Biobanking and Biomolecular Research Infrastructure (BBMRI-NL, 184.021.007; 184.033.111); The Netherlands Organisation for Scientific Research (NWO)-Netherlands Twin Registry Repository (NWO-Groot 480-15-001/674); the National Institutes of Health-The Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06), Grand Opportunity grants Integration of genomics and transcriptomics in normal twins and major depression (NIMH 1RC2 MH089951-01), and Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); and European Research Council-Genetics of Mental Illness (ERC 230374). C.B.L. declares a competing interest as editor-in-chief of Human Reproduction and his department receives unrestricted research grants from Ferring, Merck and Guerbet. All remaining authors have no conflict-of-interest to declare in regards to this work.
Trial Registration Number:
N/A.
Insights
Male microchimerism in women is not linked to male co-twins, older brothers, or sons. Age is associated with increased prevalence, suggesting other factors influence this phenomenon.
Area of Science:
- Human Genetics
- Immunology
- Reproductive Biology
Background:
- Microchimerism, the presence of cells from another zygote, is known to occur after pregnancy and is linked to certain diseases.
- However, microchimerism is also found in women without pregnancies, indicating unknown risk factors and origins.
- Understanding these factors is crucial for women's health and immunology.
Purpose of the Study:
- To investigate if having a male co-twin, older brothers, or sons increases the probability of persistent male microchimerism in females.
- To explore potential risk factors contributing to male microchimerism in women within twin pedigrees.
Main Methods:
- A cross-sectional study of 446 adult female participants from the Netherlands Twin Register (NTR).
- Analysis included female monozygotic (MZ) twins, dizygotic same-sex twins, and opposite-sex twin pairs, along with their mothers and sisters.
- Quantitative PCR assay was used to detect male-specific Y chromosome gene DYS14 in peripheral blood DNA samples.
Main Results:
- 26.9% of women had detectable male microchimerism.
- No increased risk was found for male co-twins (OR=1.23), male offspring (OR=0.90), or older brothers (OR=1.46).
- A significant positive relationship was observed between age and the presence of male microchimerism (P=0.02).
Conclusions:
- The study did not find evidence that male co-twins, male offspring, or older brothers are significant factors for male microchimerism in women.
- The positive association with age suggests that time and other unmeasured factors play a critical role in persistent microchimerism.
- Further research into the molecular underpinnings of natural chimerism is needed to understand its implications for women's health and immunology.
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