Biology concepts – dizygotic twins, assisted reproductive therapies, in vitro fertilization, oogenesis, follicles stimulation, hormones, body mass index
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.
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.
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.
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.
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.
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.
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.
overweight women also have lower levels of FSH. So there is evidence to explain why high BMI women have more twins and evidence to say it shouldn’t be happening.
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.
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 –