Unequal growth between genetically identical monozygotic (MZ)
twins in the womb may be triggered in the earliest stages of human
embryo development, according to a new study led by King's College
London.
Around 80 percent of MZ twins originate from
monochorionic/diamniotic pregnancies, where they share the same
placenta in the womb. MZ twins are recognized to be at greater risk
of congenital anomalies. One of the most common complications is
severe discordant growth, in which there is a 25 percent or greater
difference in fetal or birth weight between the twins in the
absence of twin-to-twin transfusion syndrome.
Such severe discordant growth has been reported in seven to 14
percent of all monochorionic/diamniotic pregnancies. Unequal
placental sharing can explain about half of these pregnancies; the
cause of the other half is largely unknown.
The case presented suggests that uneven growth of identical
twins could start during the early stages of preimplantation
development. An embryo donated for research revealed two inner cell
masses (ICMs, internal cluster of cells at the embryonic pole of
the blastocyst which develops into the body of the embryo), which
is a sign of monochorionic/diamniotic pregnancy that will give rise
to MZ twins. In this case, the two ICMs were not equal and
high-resolution RNA sequencing indicated that they were at
different stages of development; the smaller one was in the
earliest stages of cell lineage commitment, while the bigger one
had already differentiated to some extent. The differences in
development would become negligible; however, the difference in
size would be likely to continue throughout the pregnancy.
Laila Noli, PhD student from King's College London said: "Having
two distinct ICMs within a single embryo of which one was bigger
and more developmentally advanced than the other was an unexpected
finding. Prevailing opinion would expect them to be absolutely
identical at that stage, and that the cause of uneven growth of MZ
twins would be due to their position in the womb or other unknown
environmental circumstances at later stages of pregnancy."
Dr Dusko Ilic of King's College London, says: "Until now, the
earliest report of uneven growth of MZ twins was at 12 weeks of
pregnancy. We found that it can start virtually in the first few
days after conception. The prevalence of such early stage uneven
growth is not known and further case reports and studies are
needed. We do not know whether the two ICMs within the same embryo
may have originated from uneven splitting of a single 'parental'
ICM or whether the two ICMs formed independently. Either way, our
case report suggests that cellular and molecular events may play a
role in uneven growth of MZ twins from monochorionic/diamniotic
pregnancies."
The paper, Discordant Growth of Monozygotic Twins Starts at the Blastocyst
Stage: A Case Study, is published in Stem Cell
Reports.