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Since the s, researchers have identified more than 25 genes involved in DSDs, and next-generation DNA sequencing in the past few years has uncovered a wide range of variations in these genes that have mild effects on individuals, rather than causing DSDs.

A DSD called congenital adrenal hyperplasia CAH , for example, causes the body to produce excessive amounts of male sex hormones; XX individuals with this condition are born with ambiguous genitalia an enlarged clitoris and fused labia that resemble a scrotum.

It is usually caused by a severe deficiency in an enzyme called hydroxylase. But women carrying mutations that result in a milder deficiency develop a 'non-classical' form of CAH, which affects about 1 in 1, individuals; they may have male-like facial and body hair, irregular periods or fertility problems — or they might have no obvious symptoms at all.

Another gene, NR5A1 , is currently fascinating researchers because variations in it cause a wide range of effects 10 , from underdeveloped gonads to mild hypospadias in men, and premature menopause in women.

Many people never discover their condition unless they seek help for infertility, or discover it through some other brush with medicine.

Last year, for example, surgeons reported that they had been operating on a hernia in a man, when they discovered that he had a womb The man was 70, and had fathered four children.

Studies of DSDs have shown that sex is no simple dichotomy. But things become even more complex when scientists zoom in to look at individual cells.

The common assumption that every cell contains the same set of genes is untrue. Some people have mosaicism: they develop from a single fertilized egg but become a patchwork of cells with different genetic make-ups.

This can happen when sex chromosomes are doled out unevenly between dividing cells during early embryonic development.

For example, an embryo that starts off as XY can lose a Y chromosome from a subset of its cells. If most cells end up as XY, the result is a physically typical male, but if most cells are X, the result is a female with a condition called Turner's syndrome, which tends to result in restricted height and underdeveloped ovaries.

This kind of mosaicism is rare, affecting about 1 in 15, people. The effects of sex-chromosome mosaicism range from the prosaic to the extraordinary.

A few cases have been documented in which a mosaic XXY embryo became a mix of two cell types — some with two X chromosomes and some with two Xs and a Y — and then split early in development This results in 'identical' twins of different sexes.

There is a second way in which a person can end up with cells of different chromosomal sexes. James's patient was a chimaera: a person who develops from a mixture of two fertilized eggs, usually owing to a merger between embryonic twins in the womb.

Another form of chimaerism, however, is now known to be widespread. Termed microchimaerism, it happens when stem cells from a fetus cross the placenta into the mother's body, and vice versa.

It was first identified in the early s — but the big surprise came more than two decades later, when researchers discovered how long these crossover cells survive, even though they are foreign tissue that the body should, in theory, reject.

A study in recorded women with fetal cells in their blood as many as 27 years after giving birth 13 ; another found that maternal cells remain in children up to adulthood This type of work has further blurred the sex divide, because it means that men often carry cells from their mothers, and women who have been pregnant with a male fetus can carry a smattering of its discarded cells.

Microchimaeric cells have been found in many tissues. In , for example, immunologist Lee Nelson and her team at the University of Washington in Seattle found XY cells in post-mortem samples of women's brains The oldest woman carrying male DNA was 94 years old.

Other studies have shown that these immigrant cells are not idle; they integrate into their new environment and acquire specialized functions, including in mice at least forming neurons in the brain But what is not known is how a peppering of male cells in a female, or vice versa, affects the health or characteristics of a tissue — for example, whether it makes the tissue more susceptible to diseases more common in the opposite sex.

Scientists are now finding that XX and XY cells behave in different ways, and that this can be independent of the action of sex hormones. He and his colleagues have shown 17 that the dose of X chromosomes in a mouse's body can affect its metabolism, and studies in a lab dish suggest 18 that XX and XY cells behave differently on a molecular level, for example with different metabolic responses to stress.

The next challenge, says Arnold, is to uncover the mechanisms. His team is studying the handful of X-chromosome genes now known to be more active in females than in males.

Biologists may have been building a more nuanced view of sex, but society has yet to catch up. True, more than half a century of activism from members of the lesbian, gay, bisexual and transgender community has softened social attitudes to sexual orientation and gender.

Many societies are now comfortable with men and women crossing conventional societal boundaries in their choice of appearance, career and sexual partner.

But when it comes to sex, there is still intense social pressure to conform to the binary model. This pressure has meant that people born with clear DSDs often undergo surgery to 'normalize' their genitals.

Such surgery is controversial because it is usually performed on babies, who are too young to consent, and risks assigning a sex at odds with the child's ultimate gender identity — their sense of their own gender.

Intersex advocacy groups have therefore argued that doctors and parents should at least wait until a child is old enough to communicate their gender identity, which typically manifests around the age of three, or old enough to decide whether they want surgery at all.

This issue was brought into focus by a lawsuit filed in South Carolina in May by the adoptive parents of a child known as MC, who was born with ovotesticular DSD, a condition that produces ambiguous genitalia and gonads with both ovarian and testicular tissue.

When MC was 16 months old, doctors performed surgery to assign the child as female — but MC, who is now eight years old, went on to develop a male gender identity.

Because he was in state care at the time of his treatment, the lawsuit alleged not only that the surgery constituted medical malpractice, but also that the state denied him his constitutional right to bodily integrity and his right to reproduce.

Last month, a court decision prevented the federal case from going to trial, but a state case is ongoing. The suit will hopefully encourage doctors in the United States to refrain from performing operations on infants with DSDs when there are questions about their medical necessity, she says.

Doctors and scientists are sympathetic to these concerns, but the MC case also makes some uneasy — because they know how much is still to be learned about the biology of sex They think that changing medical practice by legal ruling is not ideal, and would like to see more data collected on outcomes such as quality of life and sexual function to help decide the best course of action for people with DSDs — something that researchers are starting to do.

Diagnoses of DSDs once relied on hormone tests, anatomical inspections and imaging, followed by painstaking tests of one gene at a time.

Now, advances in genetic techniques mean that teams can analyse multiple genes at once, aiming straight for a genetic diagnosis and making the process less stressful for families.

Vilain, for example, is using whole-exome sequencing — which sequences the protein-coding regions of a person's entire genome — on XY people with DSDs.

Vilain, Harley and Achermann say that doctors are taking an increasingly circumspect attitude to genital surgery. Children with DSDs are treated by multidisciplinary teams that aim to tailor management and support to each individual and their family, but this usually involves raising a child as male or female even if no surgery is done.

Yet if biologists continue to show that sex is a spectrum, then society and state will have to grapple with the consequences, and work out where and how to draw the line.

Many transgender and intersex activists dream of a world where a person's sex or gender is irrelevant. Although some governments are moving in this direction, Greenberg is pessimistic about the prospects of realizing this dream — in the United States, at least.

So if the law requires that a person is male or female, should that sex be assigned by anatomy, hormones, cells or chromosomes, and what should be done if they clash?

In other words, if you want to know whether someone is male or female, it may be best just to ask. James, P. A , — Arboleda, V.

Nature Rev. Sinclair, A. Nature , — Berta, P. Jordan, B. Tomaselli, S. Uhlenhaut, N. Cell , — Matson, C. Hughes, I.

El-Khairi, R. Sherwani, A. Case Rep. Tachon, G. Bianchi, D. Natl Acad. USA 93 , — Maloney, S. Chan, W.

Zeng, X. Stem Cells Dev. But we've noticed a recent uptick in the number of women who've tossed out their razors and waxing kits in favor of letting things go au natural down below.

Anecdotally speaking, lady lawns seem to be coming back into style—and it might be because more women are discovering the surprising health benefits.

It's not clear if less hair means a higher risk of STIs, but one study did link pubic hair removal to increased transmission of herpes and HPV.

Curious about some of the other wellness benefits, we asked six women who love their hairy pubes to tell us how it's boosted their physical, mental, and sexual health.

Here's why they've sworn off grooming for good. For years I felt ashamed about that, especially in my teens and early 20s—when it seemed like everyone was totally bald.

But by honoring my hair preferences, I knew I was a lot more confident in the bedroom than if I'd shaved. Because ingrown hairs suck.

When I did, I'd try to find shaving cream, post-wax oil, or some other soothing product that could prevent them.

So I finally decided to leave my hair be. I'm glad there are plenty of people and potential partners who appreciate a full bush and think it's sexy.

My advice to any woman who is growing out her pubes for the first time is to own it. Strut your stuff. Embrace your natural body state. Turns out, I loved it!

Zero irritation, no razor bumps, no weird chafing from my spandex shorts or underwear.

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