Pregnancy, microchimerism, and the maternal grandmother

Abstract

Background: A WOMAN OF REPRODUCTIVE AGE OFTEN HARBORS A SMALL NUMBER OF FOREIGN CELLS, REFERRED TO AS MICROCHIMERISM: a preexisting population of cells acquired during fetal life from her own mother, and newly acquired populations from her pregnancies. An intriguing question is whether the population of cells from her own mother can influence either maternal health during pregnancy and/or the next generation (grandchildren).

Methodology/principal findings: Microchimerism from a woman's (i.e. proband's) own mother (mother-of-the-proband, MP) was studied in peripheral blood samples from women followed longitudinally during pregnancy who were confirmed to have uncomplicated obstetric outcomes. Women with preeclampsia were studied at the time of diagnosis and comparison made to women with healthy pregnancies matched for parity and gestational age. Participants and family members were HLA-genotyped for DRB1, DQA1, and DQB1 loci. An HLA polymorphism unique to the woman's mother was identified, and a panel of HLA-specific quantitative PCR assays was employed to identify and quantify microchimerism. Microchimerism from the MP was identified during normal, uncomplicated pregnancy, with a peak concentration in the third trimester. The likelihood of detection increased with advancing gestational age. For each advancing trimester, there was a 12.7-fold increase in the probability of detecting microchimerism relative to the prior trimester, 95% confidence intervals 3.2, 50.3, p<0.001. None of the women with preeclampsia, compared with 30% of matched healthy women, had microchimerism (p = 0.03).

Conclusions/significance: These results show that microchimerism from a woman's own mother is detectable in normal pregnancy and diminished in preeclampsia, supporting the previously unexplored hypothesis that MP microchimerism may be a marker reflecting healthy maternal adaptation to pregnancy.

Figure 1. Schematic representation of strategy used to identify microchimerism.

In this example, HLA genotyping for DRB1 is shown for a proband, her mother (MP), and her fetus. Once a polymorphism unique to the MP is identified (DRB1*01 in this example), polymorphism-specific quantitative PCR can then be used to quantify MP microchimerism in DNA extracted from proband PBMC.

Figure 2. Concentration of MP microchimerism gEq in a stochastic sample of 100,000 proband gEq, among subjects with normal pregnancy, according to gestational age.

Longitudinal datapoints for each subject (n = 27) indicated by colored lines.

Figure 3. Curves indicate spline function showing model of expected concentration of MP microchimerism gEq in a stochastic sample of 100,000 proband gEq, according to gestational age.

Solid line indicates the point estimate of expected microchimerism concentration, and dashed lines indicate the 95% confidence interval. Scatterplot shows MP microchimerism concentration in proband PBMC by trimester (in gEq per 100,000 proband gEq).

Figure 4. Concentration of MP microchimerism gEq in a stochastic sample of 100,000 proband gEq, among subjects with preeclampsia compared with subgroup of subjects with normal pregnancy matched for gestational age (range 24–40 weeks) and nulliparity (n = 40 total), according to gestational age.