Unit 13. Sex and Gender

Script 38. Behaviour of the sexes

The hormone of laddishness

Oestrogen, not testosterone, is what makes a male act like a male.

In all species that practise sexual reproduction, males and females show gender-specific behaviours. These range from the way they mate to the way they defend - or fail to defend - their territory. Both males and females start out with the same template at birth, but then something acts on the male to masculinise him for life. But nobody knows just how that happens.

It is well known that sex hormones like oestrogen, which is typically seen as a female hormone, and testosterone, similarly seen as a male one, play a role in shaping the neural circuits in the developing brain, and that much of that moulding takes place before birth. It has also been established that testosterone, as well as being a fully functional hormone in its own right, can be (and often is) converted into oestrogen in the body.

Male mice experience a short-lived testosterone surge on the day they are born. It lasts less than 36 hours and the level then remains low until puberty. (In human males, there appears to be a similar neonatal surge.) This pulse of testosterone is believed to be a key event in the masculinization of the brain. Nirao Shah and his colleagues at the University of California, San Francisco wanted to find out which neurons in the brain were responding to it. What they discovered was a surprise.

It was reasonable to think, as many people did, that androgen receptors which respond to male hormones were mediating the manly transformation. But androgen receptors were found to be nearly non-existent in the brains of newborn animals. Dr Shah could not find them earlier in development either, such as just after the fetal testes first started putting out testosterone in a 13-day-old embryo. Without male hormone receptors to respond to testosterone, the researchers started to suspect androgen receptors were not the players they had been assumed to be. Nor, perhaps, was testosterone.

In their study, published this week in Neuron, the researchers decided to look at male mice which had been genetically engineered to lack androgen receptors in their nervous systems. These males still had androgen receptors in their muscles and elsewhere, so they had masculine bodies, and they experienced the testosterone surge and responded to normally circulating testosterone. But their brains were simply not able to detect it.

The mice were compared with normal males in tests of masculinity. In one, a female was put into the cage. Interestingly, the genetically modified mice still showed the classic male-mating repertoire: mounting, penetration and ejaculation. But the researchers noted that they mounted less often, were less apt to penetrate and did not stick at it for as long as the normal mice. Another test turned up similar results. Typically, a strange male entering another male's cage is met with a fight. Again, the mutant mice behaved appropriately, but they were much less aggressive, spent less time fighting and they took longer breaks between attacks. The same was found for scent-marking. Like normal males, the mutant mice urinated in various spots around their cage (unlike females, who create a single latrine). But they deposited significantly fewer urine marks than the normal males.

Because male-typical behaviours developed as the result of a burst of testosterone, but in the absence of receptors for the hormone, the researchers suspect that the testosterone in the surge is being converted into oestrogen to carry out the newborn sexual differentiation. "Masculinisation of neural pathways in response to the testosterone surge at birth proceeds primarily under the control of oestrogen," they conclude. Androgen receptors are not the master regulators for male behaviours, but rather, the researchers say, a "gain control mechanism" which amplifies such behaviours - or, when the receptors are absent, dials laddish behaviour down. (From The Economist, May 1, 2010)

Script 39. Lifespan and the sexes

Catching up

In the rich world, men are closing the longevity gap with women.

Reg Dean, who died on January 5th at the ripe age of 110, was unusual. Centenarians are rare in themselves, of course, but male centenarians particularly so. In Britain, where Mr Dean lived, five times as many women as men receive the famed card of congratulation from the queen when they celebrate their 100th birthdays. That may, however, cease to be the case in the future, for the fact that women tend to live longer than men, though still true, is less true than it was, and the gap is shrinking - in rich countries, at least - every year.

In England and Wales, the biggest peacetime difference between the life expectancies at birth of the two sexes was 6.3 years. That was in 1967. It is now 4.1 years, and falling. In the early 1980s women who made it to 65, the traditional age of retirement for British men, could expect to live four years longer than their male counterparts. The gap now is less than three years, though there is still some way to go before things return to the nine·month gap that prevailed in the 1840s, when records began. Other industrialised countries, except Japan and Russia, show something similar.

This trend is superimposed on another: that life expectancy in most developed countries has been improving for both sexes. But of late it has been improving more for men than for women.

A report about to be published by the Longevity Science Advisory Panel (a group of scientists and actuaries set up by Legal&General, an insurance company) examines the factors behind these trends.

The biggest by far is changes in the use of tobacco. Around half the difference in the longevity of the sexes can be explained by smoking. One reason why Russia bucks the trend towards equal life expectancies for the two sexes (women there live 12 years longer than men) is that its men have not followed their Western confreres and cut down on the cancer sticks.

In Britain in the 1960s, when the habit was commonplace, men were much more likely to be smokers than women. But they have also been more likely than women to give up cigarettes over the past half-century. As a result, between 1979 and 2009 male smoking-related deaths fell by 64% and the male-to-female ratio of such deaths fell from 2.1 to 1.7. Deaths from cancers of the lung, trachea and bronchus in particular fell by 39% between 1991 and 2005 among Englishmen over 49. For women the comparable figure was 3%.

A further fifth of the longevity gap between the sexes is explained by alcohol. In this case, however, the gap is widening. In 1979 two men died from alcohol-related causes for every woman who succumbed. In 2009 it was 2.4.

A third important factor is obesity - or, rather, the physiological complications obesity brings, such as high blood pressure and type 2 diabetes. On the face of things, there is little difference between the sexes in this area: 15.6% of women in the EU are obese, compared with 15.4% of men. But obesity may have a greater impact on women because it increases the risks of both hypertension and diabetes in their sex more than it does in men. And men are also closing the gap in another area related to obesity and high blood pressure: coronary heart disease. In England, deaths from this fell more than 50% between 1991 and 2005 for both men and women. But, because heart disease kills twice as many men as it does women, the reduction in the male mortality rate has been greater.

All of which is good news if you are male. Men do, nevertheless, have the deck stacked against them by biology. One way the cards are marked is that female mammals (women included) have two X chromosomes, whereas males have an X and a Y, the latter being a runty little thing with only a small complement of genes. Females' "spare" X chromosome protects them from genetic mutations on the other one. Males have no such protection. Women are thus carriers of, but rarely suffer from, diseases like haemophilia which are caused by the mutation of X-chromosome genes. In birds, by contrast, it is the males who have matched chromosomes while females sport the runt. As a result, male birds tend to outlive their mates.

A further biological difference between the sexes is in the lengths of their telomeres. These are sections of DNA that protect the ends of chromosomes from decay. Men's telomeres are shorter than those of women, and also degrade more quickly. Both of these attributes have been linked to reduced lifespans.

The biggest biological difference between health of the sexes, however, can be summed up in a single word: testosterone. Testosterone is the hormone that more or less defines maleness (though women have it too, in lesser quantities). It promotes both aggression and risky behaviour. It also suppresses the immune system, which is why castrated tomcats and rams live longer than those that have not been neutered. The same applies to people. A study on eunuchs found they live 13.5 years longer than men who are intact.

Testosterone-driven behaviour means that men are more likely than women to die in accidents, and more likely to die from the violence of others. They are also more likely to kill themselves. These things are particularly true of young adults. Men are two-and-a-half times more likely to die in their 20s than women are. Testosterone may also explain the differences between the sexes in risky behaviours like smoking and drinking.

But blaming testosterone for male risk-taking explains only the "how", not the "why". For that, you must turn to evolutionary biology. It is no coincidence that the gap between the sexes' mortality is widest in people's 20s. This is the peak period for reproduction. Men are fighting each other, and showing off to the girls, in a competition whose prize is, in an evolutionary sense, immortality itself - the passage of their genes to the next generation.

To stake a claim in the afterlife, as any religion will tell you, you must make sacrifices in the present one. In actuarial terms, therefore, the Longevity Science Advisory Panel reckons that even if men adopt healthy lifestyles, women will continue to outlive them. A gap of between one and two years of life expectancy (at age 65) will persist indefinitely. That, if you are a man, might seem unfair. But if it does, then think of it as the price of eternity. (From The Economist, January 12, 2013)

Script 40. Prehistoric reptiles

A loving mother

Family life in plesiosaurs.

The Mesozoic land was dominated by dinosaurs. At sea, though, the most abundant reptiles were the ichthyosaurs and plesiosaurs. Roughly speaking, these animals filled the ecological niches now occupied by toothed cetaceans such as dolphins and killer whales. Ichthyosaurs, indeed, looked somewhat like dolphins, though plesiosaurs - with their long necks and diamond-shaped paddles were unlike anything now alive.

Ichthyosaurs also resembled cetaceans in another way: unlike most living reptiles, which lay eggs, they gave birth to live young. For years, palaeontologists have wondered if the same was true of plesiosaurs. Now they have found out that it was - but with an interesting twist.

Robin O'Keefe of Marshall University in West Virginia has analysed a plesiosaur fossil found in Kansas in1987, which palaeontologists had suspected was a pregnant female about 4.7 metres (15 feet) long, but which had not been cleaned up and studied until last year. As he reports in Science, he found an array of tiny bones, apparently belonging to a small specimen of the same species, in the fossil's abdominal cavity. lt is unlikely that these were the remains of a meal because the bones are not broken down in the way that would be expected if they were partly digested. Instead, Dr O'Keefe believes he has discovered evidence that plesiosaurs, too, gave birth to live young.

What is more, all the baby bones come from a single individual, estimated to have been 1.5 metres long. Ichthyosaurs and other contemporary viviparous species, by contrast, gave birth to multiple offspring. The fetus's level of development indicates that it was at most two-thirds mature. Had it survived to birth it would have been about 1.8 metres in length, and about one and a half times as heavy (relative to parental weight) as the offspring of other viviparous species of the time.

That it was so heavy, and also alone, is of great interest. Georges Cuvier, an early palaeontologist, made his reputation by predicting the anatomies of newly discovered fossil species from scant evidence, such as single bones. He did so by applying to fossils the principles of comparative anatomy, asking what light the body shapes of living animals could cast on the shapes of creatures from the past. Many modern palaeontologists try to do something similar, except that what they reconstruct is behaviour.

Dr O'Keefe has performed such an analysis on his find. He starts from a fundamental observation about reproduction: you can go for quantity or quality. Having one child at a time is the ultimate expression of quality. It implies huge parental investment in the offspring since, if you lose it, you lose everything. Often, too, it implies membership of a social group, within which favours can be traded to spread the load of parenthood. Most speculatively, it might even imply a degree of intelligence - for the most intelligent mammals and birds are generally those that live in groups.

All this is a lot to load on a single fossil, of course. But it would make sense. It would mean plesiosaurs not only occupied a similar ecological niche to whales, but behaved like them, too. (From The Economist, August 13, 2011)

Script 41. Genetic damage and paternal age

Father figures

A father's age has an alarming effect on his children's genetics.

Women have to get their reproducing done early. The menopause curtails it, and even before that a woman's fertility falls significantly over the years. Men - those who can find willing partners, at least - do not suffer in quite the same way, as many stories of celebrity elder fathers testify. But perhaps such ageing Lotharios should think twice, for evidence is accumulating that their offspring are at greater than average risk of genetic disease.

The latest study to this effect has just been published in Nature by Kari Stefansson and his colleagues at deCODE Genetics, a genetic-analysis company based in Reykjavik that was founded to take advantage of Iceland's excellent medical records and its unique genealogical history. Recent immigrants apart, the relationship of almost everybody on the island to everybody else is known back as far as the first census, in 1703. In many cases it is known back to the first human settlement of the island, in 874.

Dr Stefansson's study does not reach as far back as that. He and his colleagues examined 78 trios of father, mother and child who are all still alive. In some cases they looked at grandchildren as well. Their goal was to examine the number of new mutations - traits not found in the normal body cells of either parent - in children.

The average answer is about 63. That number, however, varies widely - and the main factor involved in this variation is the age of the father. Mothers transmitted an average of 14 mutations to their children, regardless of age. Fathers showed a much wider range: 20-year-olds passed on an average of 29 mutations; 30-year-olds (the average age of fatherhood in Dr Stefansson's sample) passed on 49; and 40-year-olds passed 69.

That it is the father, rather than the mother, who causes this effect is probably because a woman's eggs are created early on, when she is still in her mother's womb, and are then put into what is, in effect, physiological deep-freeze until they are required for ovulation. Sperm, by contrast, are made continuously throughout life, and each division of their precursor cells brings risk of a misinterpretation of the DNA, and thus a mutation.

Dr Stefansson's work adds to an existing body of research on the effect of parental age. Previous studies have linked older fathers with higher rates of schizophrenia and autism in their offspring. In April three teams of researchers identified specific mutations that increase the chance of autism; all three observed that the risk of such mutations in a child rose with his father's age at conception. But Dr Stefansson and his team are the first to measure the impact of older fathers so precisely.

Modern genomics made their task easier. After sequencing the genomes of each of the people involved, tallying the new mutations in the children was simply a matter of comparing the sequences of the parents with those of their offspring. Though both mother and father contribute to a child's DNA, their contributions come in large, identifiable blocks. If a mutation is seen, its parentage is thus obvious.

There is, of course, the question of how much this matters, for most mutations have little effect - and a rare few, the stuff of evolution, are actually beneficial. According to Alexey Kondrashov of the University of Michigan, an expert on the matter who wrote an article in Nature to accompany Dr Stefansson's study, about 10% of mutations are damaging. This means that for the average baby, six of Dr Stefansson's 63 mutations are probably up to no good.

In Iceland, the average age of fathers at conception has risen from 28 in 1980 to 33 in 2011. Over the same period Dr Stefansson estimates that the number of new mutations in Iceland's newborns jumped by more than 17%.

Whether that has implications for the country's overall health remains to be seen. In the grand scheme of things, the negative effect of extra mutations is likely to be countervailed by the positive effects of modern life: better nutrition, hygiene and sanitation, as well as better medical care. But Dr Stefansson's results do give pause for thought. Some women - those undergoing cancer-related hysterectomy, for example - have eggs frozen before their operations. In the fullness of time, perhaps men will think likewise and have some of the sperm of their carefree, mutation-free youths frozen in case they fancy a little procreation in their old age. (From The Economist, August 25, 2012)