Biology concepts – dizygotic twins, assisted reproductive
therapies, in vitro fertilization, oogenesis, follicles stimulation, hormones,
body mass index
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In the 2015 movie Spy, Melissa McCarthy looks like a
housewife, but gets to prove
herself as an international
agent. Sometimes the things
that look boring really
aren’t. Fraternal twins
(dizygotic) are really much more
interesting than identical
twins (monozygotic).
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If you consider monozygotic and dizygotic twins, the
identical version appears to be more interesting on the face. Two people that look
exactly alike? That’s so cool. But on the other hand, their just a mistake of embryologic division, and that happens to lesser or greater degrees all the time.
It’s amazing that that something as difficult as making
another person can ever go right, but what if it happened twice – at the same
time in the same uterus?! Dizygotic (fraternal) twins are the truly amazing feat, and I’m going to prove
it to you.
The rates of monozygotic (MZ) twinning are the same all over
the world, but dizygotic (di = two, and zygote = fertilized eggs, DZ) twinning rates vary from place to place. What’s
more, DZ twin rates are exploding worldwide. In the US, they are up from 1 in
58 births in 1980 to 1 in 35 births in 2008. And no, it’s not just because of
assisted reproductive therapies (in vitro fertilization and things like that).
African women have more DZ twins, so it probably has a
genetic component, but tall women have more DZ twins too - so do older women,
overweight women, and women who smoked before pregnancy. Just what the heck is
going on here?
Let’s take a look and see what a female would have to do to
give her the best chance of having DZ twins. First things first - to have DZ twins, a women must release more than one egg in one fertility cycle - duh. But what controls how many eggs are released?
One factor is race and the genetics that go often travel along with race.
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DZ twinning is so common in
west Africa that is has
been put into their
mythology. The first twins supposedly
came about because a farmer
was killing monkeys, so the
monkey deities put two babies
in his wife’s belly. To keep
them safe and healthy, he had
to stop killing monkeys.
Twins are reported to carry
the fate of the family, good or
bad, so they are treated
especially well.
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Interestingly, Nigerians are different in another subtle
way. European and American women have about the same FSH levels with women who
twinned having just a bit more than women that don’t have twins. In contrast,
while all Nigerian women have much higher FSH levels, the ones that were more
likely to have twins had much higher levels of FSH than those that were not as
likely to have twins. It seems that something more might be involved, though I don't know what it is.
On the other hand, DZ twins in East Asia are exceedingly
rare. Japanese women are the least likely to have DZ twins, just under 2 births of
every 1000 in Japan are twins. And low and behold, Japanese women have the
lowest basal serum FSH levels.
But the genetic link to DZ twins doesn’t stop at race and
locality. DZ twins can run in families, while MZ twins are pretty random. Even
more perplexing, if any woman has a set of DZ twins, she becomes 4x more likely
than the control population to have another
set of DZ twins. It turns out that having DZ twins creates a permanent bump in her FSH levels, so the release of multiple eggs is more likely after having had
a set of twins.
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A disputed idea about
twinning in different parts of the
world has be to relate it to
ecology. R type species have
more offspring but invest
less in them because the harsh
environment means more will
not survive. K type species
have fewer offspring but
invest more in their nurturing.
Under Philipe Rushton’s
theory, Africans have more twins
because they act more like an
R type species. I reject this;
humans re a single species.
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But on the other hand, it seems that reducing GDF9 function
can promote DZ twinning. A 2006 study showed that there can be several mutations in the GF9
gene, some in the upstream region that controls the expression level and some
in the coding region that mcould create a shorter protein. These mutations are
found more often in women that have had DZ twins.
Just having a mutation doesn’t mean that there will be less
of the protein – sometimes a mutation can make the protein more efficient at
its job, or a mutation in the upstream region can lead to a higher expression
level. But in the case of GDF9 mutations, they seem to reduce expression.
A 2014 study showed that women (and sheep) that were heterozygotic
for a mutation that eliminated GDF9 expression had both, 1) lower serum GDF9
levels, and 2) more DZ twins. Being heterozygotic means that had one copy of
the regular gene and one of the mutant, nonfunctioning gene, so they had 50% of
the normal blood levels of GDF9. So, a protein crucial for making sure good
eggs are developed and released can also regulate how many eggs will be
released.
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Cow’s milk has high IGF-1
levels, so drinking milk may help
to promote DZ twinning. I
don’t think cat really cares about
that; it just wants a drink
without being kicked out
of it’s nine lives.
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It turns out that FSH levels are generally stable over the
reproductive years of a woman (monthly pulses excluded), but after she hits
about 35 or so, the levels start to rise. After menopause, the levels of FSH
are very high in all women, so it seems that an small increase in basal FSH
promotes twinning and fecundity, but a larger rise leads to infertility and is
a sign of menopause. It’s when FSH levels have started to rise, but before they go too high that
older women are more likely to have DZ twins.
See, I told you that DZ twins were more interesting than MZ twins – and we’re just getting started. It has been proven that tall women are more likely to have DZ twins as well. It just so happens that the countries that have the tallest women, inside and outside Africa, also have the highest DZ twinning rates.
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No one should smoke, period.
But most certainly don’t smoke
when pregnant. It leads to increased
fetal heart rate,
miscarriage, and reduce birth
weight. However, a study in 2010
indicated that
smoking before pregnancy can
increase the chance of having
DZ twins. I have no idea why.
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A secondary function of IGF-1 is to make the ovary more
sensitive to FSH. If two women have the same levels of FSH, but one has a
higher level of IGF-1, then she is more likely to have multiple ovulations in a
single cycle. Hence, tall women are more likely to have natural DZ twins – so
are cows. Cows that have more twins have 2x the level of IGF-1.
But there is another part, one that makes less sense as of
now. In women that undergo IVF and have two embryos transferred to the uterus,
the ones that are more than 1. 74 m (5 ft. 8 in.) tall are much more likely to have both embryos implant, develop and to deliver DZ twins. This isn’t
associated with multiple ovulation, so it isn’t related to ovary sensitivity to
FSH through increased IGF-1. Do taller women have uteruses of greater volume so
that there is more room for two developing fetuses? I don’t know, ask a tall woman's twins if they felt less cramped.
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Body Mass Index is supposedly
a measure of healthy weight
(mass (kg)/ height (m)2).
A BMI of over 30 or so means you’re
obese. BUT – it doesn’t take
body type or muscle mass into
account. At his body building
best Arnold Schwarzenegger
would have been considered
morbidly obese.
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And the same study that showed that double embryo transfer
in tall women resulted in more twins didn’t show the same thing for high BMI
women. If one wanted to make an
evolutionary argument, you could say that being overweight is a signal that the
environment is good enough to support more babies, so more DZ twins might
result – but that’s just speculation.
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The sextuplets from John and
Kate + Eight are now 11 years
old. Their show is off the
air, which is great for the kids, but
there are more just like it.
So, we have learned today that if you
want DZ twins or multiples -
be a tall, overweight, more than
35 year old African woman who
used to smoke – or have
multiple embryos implanted like
Kate Gosselin.
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It’s not smoking (see image above); smoking rates, even
among teenage girls are going down. Any other reason come to mind? Yep, obesity
rates are skyrocketing. This may be the biggest single reason for the great
leap in DZ twinning (along with increased access to prenatal healthcare that
may preserve more DZ twin pregnancies).
Next week – let’s dive into DZ twinning. We saw for the past
few weeks that there are many kinds of MZ twins (mosaic, parasitic, conjoined, vanished, polar body, sex discordant) – is the same true for DZ
twins? You bet.
For more information or
classroom act
ivities, see:
Dizygotic twins –
Body Mass Index –
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