Every human embryo begins with the same set of undifferentiated structures, neither male nor female, that can develop in either direction. The popular claim that “everyone starts as a girl” is a distortion of mid-20th-century science that treated female development as what happens when nothing actively pushes toward maleness. Decades of research have overturned that framing. Female development is now understood to be its own actively driven process, which means the starting point is genuinely neither sex. The story of how this myth took hold and what actually happens in the womb is more interesting than the one-liner it replaced.
Where the “Default Female” Idea Came From
The notion traces back to the French endocrinologist Alfred Jost, who in the 1940s performed groundbreaking experiments on rabbit embryos. Jost showed that if you removed the gonads from an early embryo, regardless of its chromosomes, the result was a body with female-typical anatomy: the internal ducts that form the uterus and fallopian tubes persisted, while the ducts destined to become male internal structures withered away. From this, Jost concluded that the female pattern was the “default,” and that maleness required an active push from testicular hormones.1PubMed Central. A tale of two tracts: history, current advances, and future directions of research on sexual differentiation of reproductive tracts His framework held that a “maleness factor” produces testes, those testes secrete hormones that masculinize the body, and in the absence of that factor, the gonad becomes an ovary and female anatomy follows without any special instruction.2PubMed. Genetics of sexual development: a new paradigm
Jost’s work was brilliant for its time. It correctly identified that testicular hormones are necessary for male-typical anatomy. But the leap from “removing testes produces female-looking anatomy” to “female is the default” was a logical shortcut. When you strip away the gonads, what you get isn’t a fully functional female body; it’s a body that has lost the signals pushing it in either direction, and it follows one anatomical path because those particular structures don’t require gonadal hormones to persist. The ovary, its hormones, and the genetic programs driving female development were simply left unexamined. For decades, researchers focused almost entirely on the male pathway because it was treated as the only pathway that needed explaining.
What Early Embryos Actually Look Like
For roughly the first six weeks of human development, embryos with XX and XY chromosomes are anatomically indistinguishable. The gonads exist as a pair of “bipotential” ridges, uncommitted tissue that can become either testes or ovaries. The decision point, known as primary sex determination, is when these bipotential gonads commit to one fate.3PubMed Central. An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development This is not a female state. It’s a genuinely unresolved state, maintained by a suite of genes active in both XX and XY embryos before differentiation begins.
The same principle applies to external anatomy. The genital tubercle, a small mound of tissue present in all early embryos, is the common precursor to both the penis and the clitoris.4PubMed Central. Development of the human penis and clitoris There are also two sets of internal ducts present simultaneously: one set (Müllerian ducts) that can form the uterus and fallopian tubes, and another (Wolffian ducts) that can form the vas deferens and related structures. Both sit there waiting for signals. Calling this starting arrangement “female” is like calling a lump of clay a vase because it hasn’t been shaped into a bowl yet.
How the Male Pathway Gets Activated
In embryos with a Y chromosome, the gene SRY acts as a trigger. It’s expressed briefly in cells of the bipotential gonad and activates another gene, SOX9, which then sustains the cascade that turns those cells into Sertoli cells, the key cell type in the developing testis.5PubMed. SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors SRY itself is only active for a short window, but the genes it triggers keep running.6PubMed. SRY upregulation of SOX9 is inefficient and delayed, allowing ovarian differentiation, in the B6.Y(TIR) gonad
Once testes form, they produce two critical hormones. Anti-Müllerian hormone (AMH), made by those Sertoli cells, causes the Müllerian ducts to break down, eliminating the structures that would otherwise become the uterus and fallopian tubes.7PubMed. Anti-Müllerian hormone, beta-catenin and Müllerian duct regression The Müllerian duct, left alone, would develop into the oviducts, uterus, and upper vagina; AMH’s job is specifically to prevent that.8PubMed Central. The mechanisms underlying the effects of AMH on Müllerian duct regression in male mice Meanwhile, testosterone from the fetal testes stabilizes the Wolffian ducts and promotes their development into male internal reproductive structures. For external genitalia, testosterone gets converted into a more potent form called dihydrotestosterone (DHT), which shapes the genital tubercle into a penis and drives formation of the prostate and urethra.9PubMed Central. The effect of 5α-reductase-2 deficiency on human fertility
This pathway is well-mapped and genuinely active. But Jost’s error wasn’t in describing the male pathway. It was in assuming the female pathway was just the absence of these signals.
Female Development Is Not Passive
Research over the past two decades has made it clear that ovarian development requires its own set of active genetic signals. The gene WNT4 is one of the best-studied factors in the ovarian-determination pathway. It works on multiple fronts: suppressing the male differentiation program, promoting the development of Müllerian ducts, and maintaining the health of egg cells.10PubMed. WNT4, RSPO1, and FOXL2 in sex development WNT4 doesn’t just sit there; it’s actively regulated by another signaling molecule called RSPO1. In mouse studies, when RSPO1 was knocked out in XX embryos, the expression of WNT4 and its downstream targets collapsed, and the gonads lost their female-specific gene expression pattern.11Human Molecular Genetics. R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling
Even after the ovary forms, its identity has to be actively maintained. The transcription factor FOXL2 works throughout life to keep ovarian cells from flipping toward a testicular fate. It does this partly by mobilizing estrogen signaling and partly through independent mechanisms that repress SOX9, the same gene that drives testis formation.12PubMed Central. The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells In other words, female development doesn’t just happen because male signals are absent. It requires ongoing genetic effort to build and preserve ovarian tissue. The old “default” model missed all of this because no one was looking for it.
A recent interdisciplinary review put it bluntly, arguing for a model that defines female sex development as an active, regulated process rather than a default state, and one that opens the door to more research on estrogen-dependent differentiation.13PubMed Central. The persisting presence of absence in female sex development: a critical interdisciplinary reflection
Why Male Nipples Don’t Prove the “Default Female” Theory
The existence of nipples on men is probably the single most-cited piece of “evidence” for the idea that everyone starts as female. The reasoning seems intuitive: nipples are useful for breastfeeding, breastfeeding is a female function, so nipples must be a leftover from the “female stage.” But this gets the logic backward. Nipple formation begins early in development, before the hormonal divergence that differentiates sex. They form from the mammary ridge around week four or five, well before SRY has done its work and before the gonads produce any hormones at all. Both sexes develop nipples not because the embryo is female, but because nipple formation occurs during the bipotential period when sex hasn’t been determined yet. There’s no selective pressure to remove them from males because the genetic cost of doing so would be high: you’d need to decouple the developmental program that builds nipples from the one shared by both sexes, and evolution generally doesn’t bother with that kind of rewiring when the structure is harmless.
In the same way, the fact that the clitoris and penis share a common precursor doesn’t mean the starting state is “female.” Both structures emerge from the same tissue; hormones determine which direction it grows. The external genitalia of very early embryos look similar in both sexes precisely because differentiation hasn’t occurred, not because the embryo is one sex or the other.
Conditions That Reveal How the Pathways Work
Some of the clearest evidence against the “default female” model comes from variations in sex development, conditions where one step in the differentiation cascade doesn’t go as expected. These aren’t defects in a “default” system; they’re windows into a finely tuned process that has multiple points where outcomes can diverge.
In complete androgen insensitivity syndrome (CAIS), a person has XY chromosomes and functioning testes that produce testosterone, but their cells cannot respond to androgens. The result is an individual with a 46,XY karyotype and an outwardly feminine appearance: female-typical external anatomy, but no uterus or ovaries.14Archives of Medical Science. The challenges of androgen insensitivity syndrome In documented families, multiple siblings with CAIS presented with primary amenorrhea, elevated testosterone levels, and confirmed XY genotype with the SRY gene present.15PubMed. Familial complete androgen insensitivity syndrome (CAIS): a case series of three siblings with emphasis on diagnosis, management, and psychosocial outcomes CAIS shows that the presence of testes and testosterone alone isn’t enough for male anatomy; the body’s ability to read those hormonal signals is what matters. And the absence of a uterus in these individuals shows that the Müllerian ducts were indeed broken down by AMH from the testes, meaning the male pathway partially succeeded while the androgen-dependent steps didn’t.
A different condition, 5-alpha-reductase 2 deficiency, produces a nearly opposite picture in some respects. Here, individuals with XY chromosomes can produce testosterone but cannot efficiently convert it to DHT. Because DHT is the hormone that shapes external genitalia during fetal development, affected individuals are often born with ambiguous or female-typical external anatomy and are raised as girls. But at puberty, the surge in testosterone itself is enough to trigger virilization, and most affected males go on to identify as male.16PubMed. Steroid 5α-reductase 2 deficiency Internally, the Wolffian ducts have already developed under the influence of testosterone during fetal life, and the Müllerian ducts have regressed due to AMH. So the internal reproductive tract is male, while the external anatomy initially wasn’t.
There’s also the rare condition known as de la Chapelle syndrome, where individuals with a 46,XX karyotype develop male external genitalia (ranging from typical to atypical) along with testes, usually because the SRY gene has been translocated onto an X chromosome or an autosome. Imaging in such cases sometimes reveals a Müllerian remnant alongside the testes, showing the competing signals playing tug-of-war within a single body.17PubMed Central. A Case of de la Chapelle Syndrome
The Brain Develops on Its Own Timeline
Sexual differentiation isn’t a single event; it’s a series of events spread across different tissues at different times. The genitals differentiate in the first two months of pregnancy, while the brain’s sexual differentiation begins in the second half.18PubMed. Sexual differentiation of the human brain in relation to gender identity and sexual orientation Because these two processes happen months apart and can be influenced independently by hormonal environments, the outcome in one doesn’t guarantee the outcome in the other. This is part of the biological basis researchers have explored in understanding gender identity, though the picture remains complex and involves factors well beyond any single hormone surge.
The maternal hormonal environment itself changes depending on fetal sex. Women carrying male fetuses show higher levels of certain inflammatory and angiogenic factors throughout pregnancy, while women carrying female fetuses show higher levels of certain regulatory immune signals.19PubMed Central. Fetal Sex-Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period The fetus and the mother are in constant biochemical conversation, and the sex of the fetus shapes that conversation from early on. This isn’t what you’d expect if the embryo were simply sitting in a neutral “female” state waiting for a switch to flip.
How Other Animals Handle Sex Determination
The mammalian system, with its XY chromosomes and SRY gene, is only one of many ways animals sort out sex. Looking at other species makes the “default female” idea even harder to sustain, because the very concept of which sex is “default” depends entirely on the system being used.
In birds, the chromosome system is flipped. Males carry two copies of the same sex chromosome (ZZ), while females carry one of each (ZW). The key sex-determining gene in birds is DMRT1, located on the Z chromosome. Males need two copies of DMRT1 for normal testis development. When researchers used gene editing to knock out one copy of DMRT1 in ZZ chicken embryos, those genetically male birds developed ovaries instead of testes.20PubMed Central. Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics In other words, maleness in birds requires a double dose of a specific gene, and reducing that dose pushes development toward the female pathway.21PubMed. The avian Z-linked gene DMRT1 is required for male sex determination in the chicken If you tried to apply the “default” framework here, you’d have to argue that the default in birds is male, since the female is the one who needs a special chromosome (W). The whole concept of a default sex just doesn’t hold up across species.
Many reptiles sidestep chromosomes entirely. In species with temperature-dependent sex determination, the incubation temperature during a critical window of embryonic development determines whether the gonads become ovaries or testes. Estrogens and the enzyme aromatase, which converts androgens into estrogens, play a central role in ovary formation during this window. Even small differences in aromatase activity can produce intersex gonads, suggesting that the balance between male and female pathways is remarkably delicate.22PubMed. Temperature-dependent sex determination and gonadal differentiation in reptiles
Fish That Change Sex Entirely
If the mammalian system makes the “default female” idea questionable, sequential hermaphroditism in fish blows it out of the water. Many teleost fish species can change sex during their adult lives, triggered by social context, age, or body size. In protogynous species (those that start as female and become male), the entire gonad undergoes remodeling: ovarian tissue degenerates and is gradually replaced by testicular tissue.23PubMed Central. Action of the Metalloproteinases in Gonadal Remodeling during Sex Reversal in the Sequential Hermaphroditism of the Teleostei Fish Synbranchus marmoratus
Researchers have established laboratory models for studying this process. In the New Zealand spotty wrasse, complete female-to-male transition was induced in captivity either by blocking aromatase (the enzyme that produces estrogens) or by manipulating social group composition, with full transition occurring in about 60 days.24PubMed Central. A new experimental model for the investigation of sequential hermaphroditism The fact that blocking estrogen production can trigger a sex change in these fish reinforces the broader point that femaleness is actively maintained by molecular signals. Remove those signals and the tissue can reorganize. Sex, across vertebrates, is less a fixed identity stamped at conception and more an ongoing negotiation between competing genetic and hormonal programs.
What Organoid Research Is Revealing
One reason the “default female” model persisted so long is that it’s genuinely difficult to study the earliest stages of human gonad development. You can’t experiment on human embryos the way Jost experimented on rabbits. Recent advances in organoid technology are changing that. Researchers have developed three-dimensional culture systems using human stem cells that can model early gonad formation in a dish, letting scientists watch the bipotential stage play out and test what signals push it toward testis or ovary formation.25PubMed Central. Modeling Human Gonad Development in Organoids These systems are still in their early stages, but they offer the first real opportunity to study human sex determination in controlled conditions rather than extrapolating from animal models. Given that a large fraction of what we “know” about human sexual differentiation comes from mice, rabbits, and chickens, this kind of direct human data could reshape the field over the next decade.
The old story was clean and memorable: you start as a girl, and the Y chromosome intervenes to make some of us boys. The real biology is messier and more fascinating. Both pathways are built on active genetic programs that have to run correctly, be maintained over time, and can be disrupted at multiple points. Neither sex is a passive leftover. The embryo doesn’t start as anything but an embryo.