Prenatal influences on the lives of twins: fertility

Reading some of the recent books on post-Columbian disease exchange, I have been impressed by the contribution of basic historical demographic research to understanding biological processes. Colonial records have allowed people to arrive at much better estimates of the catastrophic death toll of indigenous people in Latin America. Later in time census records show similar effects in Hawaii, for example. This documentary evidence has given new credence to the reports of very early explorers, who described vast native populations much larger than existed only a generation after contact.

But disease is not the only biological topic on which historical records are making an impact. A number of papers in the last few years have used historical records to investigate correlations between life history traits. For example, does birth order make a difference to reproductive success/offspring number? Do older siblings live longer? What about twins?

A new paper by Virpi Lummaa and colleagues used records from Finland to demonstrate a curious fact about twins: females with a male twin have fewer offspring than females with a female twin. What's more, having a female twin makes no difference for males, it only makes a difference for the female.

This effect is quite large: females who had a female co-twin had a 90 percent chance of reproducing during their lifetimes, and had an average of around 3.5 children; females with a male co-twin had less than a 70 percent probability of reproducing, and an average of less than 2 offspring. The effect is large enough to depress the fitness of mothers of opposite-sex twins from 15 to around 12 grandchildren.

The paper has a number of reasons for attributing the effect to prenatal factors:

If the differences were caused by postnatal masculinization or social-preference effects, we would expect that females would do better if their male co-twin dies shortly after birth and the females are raised after birth as singletons. In contrast, we found no evidence to suggest that daughter success improves if their male co-twin dies shortly (within 3 months) after birth. Females born with a male co-twin but raised as singletons after birth still have impaired lifetime fecundity and lifetime reproductive success compared to females born with a female co-twin but raised as singletons. This result makes it difficult to interpret our findings as after-birth social or parental-preference effects. This point is further emphasized by the fact that we failed to detect a significant interaction between social class and success of females with a male co-twin: In many societies, females can be preferred over males among lower classes, whereas males can be preferred among the upper classes (33). Finally, that the death of a male co-twin shortly after birth fails to improve female success also provides further support for the idea that reduced female success is not because of females simply being outcompeted by male co-twins nutritionally because the greatest nutritional demand of growing infants is not during gestation, but during late lactation (34) (Lummaa 2007:10918).

The discussion of experimental data on prenatal hormonal influences is useful:

In rodents, female fetuses positioned between two males have higher levels of testosterone than those from the same litter positioned bet ween females (9). Further more, such females commonly have greater (i.e., more male-like) anogenital distances and of ten show more aggression, delayed maturation, longer estrus cycles, reduced sexual attractiveness to males, and shorter reproductive lifespans (9). Given that testosterone is lipid-soluble, there is no basis for assuming that interfetal transfer of testosterone, unequivocally demonstrated in rodents, will not occur in any multiparous mammal. Thus, in humans, sex hormones are also likely to diffuse across fetal membranes and amniotic fluid, leading to the likelihood that human twins also can be influenced hormonally by the presence of a co-twin (13). In accordance, human twin studies have shown that having a male co-twin can be associated with increased female growth in utero (14, 15) and masculinization of sexually dimorphic anatomical traits known to be sensitive to testosterone concentrations during fetal development, including second- to fourth-digit finger ratio (16), auditory system (17), craniofacial growth (18), visual acuity (19), and canine size (20). In addition, such females commonly show more male-like behaviors and attitudes after birth (11).
Therefore, a male cosibling can have significant effects on the subsequent morphology and behavior of females in humans and other mammals. However, it is currently unknown whether hormonal interactions between fetuses can also have consequences for offspring reproductive success and maternal fitness in humans or natural populations of wild animals (10), although evidence in laboratory rodents suggests that this might be the case (21) (Lummaa et al. 2007:10915).

Something to keep in mind in discussions of epigenetics and development, particularly from twin studies. Prenatal influences have important long-term effects on life history.

(via Gene Expression)

UPDATE (6/19/2007): A reader directs my attention to the freemartin: when a cow bears twins, one a bull calf and the other a heifer, the heifer is often sterile. She is called a "freemartin." Freemartin have been important in various kinds of research -- not least, farmers have historically used them to detect estrus in their cows. You see, a freemartin will mount a cow in estrus, but not harm her as a bull might.

The discovery that freemartins always have male twins is attributed to John Hunter, who described them in a 1779 article:

It is a known fact, and, I believe, is understood to be universal, that when a cow brings forth two calves, and that one of them is a bull-calf, and the other a cow to appearance, the cow-calf is unfit for propagation; but the bull-calf becomes a very proper bull. They are known not to breed: they do not even shew the least inclination for the bull, nor does the bull ever take the least notice of them.
This cow-calf is called in this country a free martin; and this singularity is just as well known among the farmers as either cow or bull.
This calf has all the external marks of a cow-calf similar to what was mentioned in the unnatural hermaphrodite, viz. the teats and external female parts, called by farmers the bearing.
When they are preserved it is not for propagation, but for all the purposes of an ox or spayed heifer, viz. to yoke with the oxen, and to fatten for the table (Hunter 1779:285).

A more modern description of freemartins is given by Padula (2005). Freemartins are not a universal consequence of heterosex twinning in cattle -- sometimes the heifer is normal. Also, it happens in other species, including sheep and goats. It turns out to be a form of chimerism, with cells from the male twin colonizing the female:

The freemartin condition represents the most frequent form of intersexuality found in cattle, and occasionally other species. This review considers the current state of knowledge of freemartin biology, incidence, experimental models, diagnosis, uses for freemartins in cattle herds, occurrence in non-bovine species, effects on the male, and highlights potential new research areas. Freemartins arise when vascular connections form between the placentae of developing heterosexual twin foeti, XX/XY chimerism develops, and ultimately there is masculinisation of the female tubular reproductive tract to varying degrees. With twinning rates in Holstein cows increasing, there will be greater economic importance to establish early diagnosis of the freemartin and the detection of the less common single born freemartin. New diagnostic methods based on the detection of Y-chromosome DNA segments by polymerase chain reaction (PCR) show improved assay sensitivity and efficiency over karyotyping and clinical examination. The implications for the chimeric male animal born co-twin to the freemartin are contentious as to whether fertility is affected; if germ cell chimerism does indeed occur; and, if there are any real effects on the sex ratio of offspring produced. In beef cattle, the freemartin carcass has similar characteristics to normal herdmates. Hormonal treatment of freemartins for use as oestrous detectors has been used to obtain salvage value. The biology of freemartin sheep has recently been studied in detail, and the condition may be increasing in prevalence with the introduction of high fecundity genes into flocks. Potential new research areas are discussed, such as detection of foetal DNA in maternal circulation for prenatal diagnosis and investigation of the anti-tumour properties of Mullerian inhibiting substance (MIS). The freemartin syndrome will always be a limiting factor in cattle and to a lesser extent in sheep production systems that have the goal to produce multiple reproductively normal female offspring from a single dam without using sex predetermination.

References:

Hunter J. 1779. Account of the free martin. Phil Trans Roy Soc Lond 69:279-293.

Lummaa V, Pettay JE, Russell AF. 2007. Male twins reduce fitness of female co-twins in humans. Proc Nat Acad Sci USA 104:10915-10920. doi:10.1073/pnas.0605875104

Padula AM. 2005. The freemarti syndrome: an update. Anim Reprod Sci 87:93-109.