Impact of Number of Pregnancies on Maternal MicrochimerismCasey
TrimmerYork College Department of Biological Sciences Normally,
every cell in an organism contains the exact same set of genetic
material, as all of the cells of the body originate from one
initial cell that copies its genetic material again and again.
Chimerism is a condition in which an individual is composed of more
than one set of genetic information; some cells contain one set,
while other cells contain another. Microchimerism is a term used to
describe this chimerism on a smaller scale: the genetic material in
a small population of a persons cells differs from the material in
the rest of the cells (Turco and Bambara 2004). The phenomenon of
cells passing back and forth between mother and fetus during
pregnancy is termed fetomaternal cell trafficking (Scaletti et al.
2001). This exchange between mother and fetus is a cause of
microchimerism, as a small population of fetal cells enters the
body of the mother and vise versa. It had been assumed these
foreign cells were quickly destroyed by the hosts immune system.
However, recently it has been shown that these cells can persist
for long periods of time (Nelson 2002, Bianchi et al. 1996), a
condition termed persisting fetal microchimerism. This discovery of
a foreign population of cells circulating though the bodies of
mother and child has been the focus of recent research in
autoimmune disorders. Research in microchimerism searches for the
presence of male cells in women that had male pregnancies, as male
DNA in a female is a clear indication of foreign DNA. Research has
consistently shown that fetal cells persist in the mothers body for
an extended period of timeperhaps the mothers entire life (Lee
2001). However, no research has been conducted on how the number of
male pregnancies a woman has affects the frequency of autoimmune
disorders or the frequency of finding foreign cells in her body.
The objective of this study is to determine whether the number of
pregnancies is related to the incidence of finding foreign cells in
the body. I hypothesize that a greater number of male pregnancies
would result in more cell exchanges between fetus and mother,
thereby increasing the frequency of finding chimeric cells in the
mother. REVIEW OF LITERATURERESEARCH DESIGNOBJECTIVE AND
HYPOTHESISObjective:Examine how the number of male pregnancies
affects the frequency of finding male (foreign) DNA in the
mother
Hypothesis:A greater number of pregnancies would result in more
cell exchanges between fetus and mother, thereby increasing the
frequency of finding chimeric cells in the mother.Male cells have
been found to exist in womens blood for decades after pregnancy
with a male child (Bianchi et al. 1996, Invernizzi et al. 2000).
Presence of foreign cells in the body has been examined as a
possible cause of autoimmune disorders. Research regarding
autoimmune thyroid disorders (Table 1) shows presence of male cells
in diseased thyroids and blood from patients with multiple
disorders (Srivatsa et al. 2001, Klintschar et al. 2001, Ando et
al. 2002).
Research concerning the autoimmune liver disorder primary
biliary cirrhosis (Table 2) found that male fetal cells persisted
in the liver and blood of both control and disease women (Tanaka et
al. 1999, Invernizzi et al. 2000)
Research regarding the autoimmune disease scleroderma (Table 3)
has shown male cells to be present in the blood of disease and
control women (Nelson et al. 1998, Arlett et al. 1998, Evans et al.
1999, Artlett et al. 2000, and Lambert et al. 2000).
TABLE 3. Frequency of male cells in disease and control groups
for sclerodermaTABLE 2. Frequency of male cells in disease and
control groups for PBCTABLE 1. Frequency of male cells in disease
and control groups for thyroid disorders.1 Srivatsa et al. (2001)2
Klintschar et al. (2001)3 Ando et al. (2002)
1 Invernizzi et al. (2000)2 Tanaka et al. (1999)1 Nelson et al.
(1998))2 Artlett et al. (1998) 3 Evans et al. (1999)4 Artlett et
al. (20005 Lambert et al. (2000)
EXPECTED RESULTSINTRODUCTION(Scaletti et al. 2001)Research
GroupsChimeric cell groupsN=20 women (30-45 yrs old)
4 women w/ 1 son4 women w/ 2 sons4 women w/ 3 sons4 women w/ 4
sons4 women w/ 5 sons DNA extraction from blood samples PCR
Amplification of Y-chromosome specific sequence Gel electrophoresis
to visualize PCR resultsControl groupsN=12 (30-45 yrs old)
4 women never pregnant4 women only pregnant w/ females4
menExpected gel:(Invernizzi et al. 2000)Base pair ladderNo band no
male DNABand male DNAMale sample verification of PCRPossible
relationships between number of male pregnancies and frequency of
finding male DNA Direct relationship: As number of male pregnancies
increases, the frequency of finding male cells increases.
Saturation of cells: reach a certain number of male pregnancies
where frequency of finding male cells will not increase No
relationship: The frequency of finding male cells is unrelated to
number of male pregnanciessame frequency for all number of
pregnancies No relationship: The frequency of finding male cells is
unrelated to number of male pregnanciesrandom frequency of finding
male cells (affected by other factors) Possible other factors:
older male siblings, unknown miscarriage, blood transfusion, organ
transplant
Cells obtained from:Frequency of disease group w/ male
cellsFrequency of control group w/ male cells
Blood1100% (n=17)70% (n=23)Skin Lesions 2 58% (n=19)0%
(n=7)Blood 246% (n=69)4% (n=25)Blood 360% (n=20)31% (n=48)Blood
465% (n=63)28% (n=88)Blood 542% (n=12)47% (n=19)
Cells obtained fromFrequency of disease group with male
cellsFrequency of control group w/ male cells
Blood 136% (n=36)31% (n=36)Liver 270% (n=37)72% (n=31)
Cells obtained fromDisorderFrequency of disease group w/ male
cellsFrequency of control group w/ male cells
Thyroid 1Various55% (n=29)0% (n=18)Thyroid2Hashimotos
Thyroiditis47% (n=17)4% (n=25)Blood3Graves Disease47% (n=17)29%
(n=30)
