Every human embryo spends its first several weeks in a sexually undifferentiated state, carrying the anatomical precursors for both male and female reproductive structures. This observation gave rise to the popular claim that “we all start out as female,” but that framing overstates what is actually happening. The embryo is not female in any meaningful sense; it is bipotential, equipped with two parallel sets of internal ducts and a set of external structures that have not yet committed to either path. What happens next depends on a cascade of genetic signals and hormones, and the science behind that cascade has shifted considerably since the mid-twentieth century, when the “default female” model first took hold.
Where the “Default Female” Idea Came From
The notion traces back to the pioneering work of French endocrinologist Alfred Jost in the 1940s. By removing the gonads from rabbit embryos at various stages, Jost showed that without testes and the hormones they produce, a fetus develops female-appearing anatomy regardless of its chromosomes. His conclusion was straightforward: testosterone and a second testicular hormone (now called anti-Müllerian hormone, or AMH) actively impose male characteristics, while the female body plan emerges in their absence.1PubMed. Professor Alfred Jost: the builder of modern sex differentiation This framework dominated reproductive biology for decades and is still the version most people encounter in introductory biology courses. Jost’s experiments were real and reproducible, and the paradigm he built from them shaped the entire field of sex differentiation.2PubMed Central. A tale of two tracts: history, current advances, and future directions of research on sexual differentiation of reproductive tracts
The problem is not that Jost was wrong about what he observed. Remove the testes and the embryo does develop along female-typical anatomical lines. The problem is with the word “default.” Calling femaleness a default implies it requires no active biological work, that it simply happens when nothing else intervenes. Researchers now know that is not the case.
Why “Default” Gets It Wrong
Over the past two decades, molecular studies have identified a growing list of genes that actively drive ovarian development. FOXL2, WNT4, and RSPO1 are among the best characterized. FOXL2, for instance, plays a direct role in pushing supporting cells in the early gonad toward an ovarian fate, actively suppressing male-pathway markers like SOX9 in the process.3PubMed Central. FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development The ovary does not just passively form when the testis pathway fails to activate. It has its own genetic program that must be switched on and maintained. Researchers have described ovarian organogenesis as an active, regulated process rather than one that arises by default.4PubMed Central. The pathway to femaleness: current knowledge on embryonic development of the ovary
A 2026 review went further, arguing that the persistence of the “default” framing has actually held back research on female-specific developmental mechanisms, particularly the role of estrogen signaling in sex differentiation. The authors called for a less reductionist model that treats female sex development as worthy of its own research agenda.5PubMed Central. The persisting presence of absence in female sex development: a critical interdisciplinary reflection The older model was not so much disproven as revealed to be incomplete. Male development is indeed hormonally driven in dramatic, visible ways. But female development also requires active gene expression; it is just that the research community was slower to discover and characterize those pathways.
The Genuinely Undifferentiated Stage
For roughly the first six weeks after fertilization, XX and XY embryos look the same in terms of their reproductive anatomy. Both carry a pair of structures called the genital ridges, which are the precursors to either testes or ovaries. Both have two parallel sets of internal ducts: the Wolffian ducts (which can become male reproductive plumbing) and the Müllerian ducts (which can become the uterine tubes, uterus, and upper vagina). And both have a genital tubercle externally, a small mound of tissue that will eventually become either a penis or a clitoris depending on hormonal signals.
This truly bipotential stage is what people are usually referring to when they say “we all start as female.” But calling it female is a misnomer. An undifferentiated embryo has not adopted a female phenotype. It has not yet adopted any phenotype. It is more accurate to say that it carries the raw materials for both possibilities, and neither pathway has started in earnest.
How Male Development Gets Triggered
The fork in the road begins with the SRY gene on the Y chromosome. Around week six or seven, SRY activates in the cells of the genital ridge of XY embryos and triggers a cascade that pushes the bipotential gonad toward becoming a testis. SRY’s most critical downstream partner is SOX9, which sustains and amplifies the testis program after SRY’s own expression window closes. Research has shown that SOX9 takes over a large portion of SRY’s regulatory targets, ensuring that testis development continues even though SRY itself is only active for a brief window.6Cell Reports. The Sex-Determining Factors SRY and SOX9 Regulate Similar Target Genes and Promote Testis Cord Formation during Testicular Differentiation Additional signals including FGF9 work alongside SOX9 to reinforce the testis pathway.7PubMed Central. SRY and the standoff in sex determination
Once the testis forms, it begins producing two hormones that reshape the rest of the body. Testosterone, made by Leydig cells, stabilizes the Wolffian ducts and later masculinizes the external genitalia. AMH, made by Sertoli cells, causes the Müllerian ducts to regress. Without both of these hormones acting in the right tissues at the right times, male-typical anatomy does not develop, even in an XY embryo.
Two Sets of Internal Ducts
The dual-duct system is one of the clearest illustrations of the bipotential starting point. Every embryo begins with both Wolffian and Müllerian ducts running alongside each other. In a typical male, testosterone stabilizes the Wolffian ducts, which then differentiate into the epididymis, vas deferens, and seminal vesicles.8Hormone Research. Regulation of Wolffian Duct Development Meanwhile, AMH from the developing testes signals the Müllerian ducts to break down and disappear.9PubMed Central. The mechanisms underlying the effects of AMH on Müllerian duct regression in male mice
In a typical female, the absence of testosterone means the Wolffian ducts are not stabilized, and they degrade on their own. The Müllerian ducts, free from AMH-driven regression, persist and differentiate into the uterine tubes, uterus, and upper vagina.10PubMed Central. The Development of the Human Female Reproductive Tract. Part 1: Uterine Tube and Uterus That differentiation is itself regionally patterned by Hox genes: different members of the Hoxa cluster are expressed in different segments, with Hoxa-9 in the fallopian tubes, Hoxa-10 and Hoxa-11 in the uterus and cervix, and Hoxa-13 in the upper vagina.11PubMed. A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes This is another piece of evidence that female tract development is not just “Müllerian ducts surviving by default.” The regional specialization of those ducts into distinct organs requires its own set of genetic instructions.
The sensitivity of the Wolffian duct system to androgens is striking. Research using androgen-blocking drugs in rats has shown that while simply stabilizing the Wolffian ducts requires only modest androgen levels, the subsequent differentiation of those ducts into distinct organs is far more susceptible to disruption if androgen signaling is blocked.12Endocrinology. Androgen-Dependent Mechanisms of Wolffian Duct Development and Their Perturbation by Flutamide Keeping the ducts alive is one thing; building functional organs from them is a much more demanding hormonal process.
How the External Genitalia Diverge
The external genitalia share a common origin in both sexes. Around week seven, male and female embryos both have a genital tubercle, urethral folds, and labioscrotal swellings. In males, a potent form of testosterone called dihydrotestosterone (DHT) drives the fusion of the urethral folds and the growth of the genital tubercle into a penis. Blocking the enzyme that converts testosterone to DHT results in incomplete masculinization of external genitalia even in XY animals, demonstrating that testosterone alone is not enough.13PubMed. The development of a male pseudohermaphroditic rat using an inhibitor of the enzyme 5 alpha-reductase
In females, without androgen stimulation, the same structures take a different path. The vestibular plate canalizes to form a wide vestibular groove whose edges remain unfused, becoming the labia minora.14PubMed Central. Development of the human penis and clitoris The clitoris and labia majora become identifiable at roughly seven weeks, with the clitoral hood forming between ten and fourteen weeks.15PubMed Central. The development of the external genitals in female human embryos and foetuses. Part 1: Perineal thick skin, clitoris and labia These structures are homologous to their male counterparts, meaning they derive from the same embryonic tissue. The glans of the clitoris corresponds to the glans of the penis, the labia majora correspond to the scrotum, and so on. This shared origin is the kernel of truth behind “we all start as female,” but it is more accurate to say that both sets of genitalia are variations on a single undifferentiated template.
What Happens When the Usual Pathways Are Disrupted
Some of the most revealing evidence about how sex differentiation works comes from conditions where the process unfolds differently than expected. These conditions, collectively called differences in sex development (DSDs), are not abnormalities in the sense of something going haywire. They are natural variations in the biological pathways described above, and they illuminate how finely tuned the system normally is.
In complete androgen insensitivity syndrome (CAIS), a person has XY chromosomes and functioning testes that produce testosterone, but their cells cannot respond to androgens because the androgen receptor is nonfunctional. The result is a person with a 46,XY karyotype and an outwardly female phenotype.16Archives of Medical Science. The challenges of androgen insensitivity syndrome The testes still produce AMH, so the Müllerian ducts regress, meaning there is no uterus or upper vagina. But because androgen signaling cannot occur, the Wolffian ducts also fail to develop, and the external genitalia follow the non-androgenized path. CAIS is powerful evidence for the hormonal model: without functional androgen signaling, XY chromosomes alone cannot produce male anatomy outside the gonads.
Swyer syndrome operates differently. Here the SRY gene is mutated or absent, so the gonads never become testes in the first place. The person has XY chromosomes but develops streak gonads that produce neither testosterone nor AMH. With no AMH, the Müllerian ducts persist and form a uterus and uterine tubes. With no testosterone, the external genitalia develop along female-typical lines.17PubMed Central. The Mysteries of Primary Amenorrhea: Swyer Syndrome People with Swyer syndrome can sometimes carry pregnancies using donated eggs, because they have a functional uterus.
Running in the opposite direction, some people with XX chromosomes develop testes and a male phenotype because a fragment of the Y chromosome carrying SRY has been translocated onto one of their X chromosomes. These individuals typically have male external genitalia and are often identified only when they experience infertility, because the rest of the Y chromosome’s fertility-related genes are absent.18PubMed Central. Sex-determining Region of Y-gene Translocation and 46,XX Testicular Disorders of Sex Development: Cytogenetic and Molecular Insights into Male Infertility Research has shown that in many of these cases, the X chromosome carrying the SRY fragment is preferentially kept active through skewed X-inactivation, allowing SRY to be expressed at levels sufficient for full masculinization.19PubMed. Skewed X-chromosome inactivation pattern in SRY positive XX maleness: a case report and review of literature
Together, these conditions underscore that sex differentiation is not a simple toggle between two options. It is a chain of events where gonads, hormones, receptors, and target tissues all need to align, and when any link in the chain diverges, the outcome shifts in ways that cannot be reduced to “male or female by default.”
The Brain Does Not Follow a Single Script Either
Structural and functional differences between male and female brains are well documented, though they are statistical trends across populations rather than binary categories. The old assumption, consistent with Jost’s framework, was that all of these differences arise from prenatal hormone exposure. If testosterone masculinizes the body, the reasoning went, it must also masculinize the brain, and without it the brain develops along female-typical lines.
The story turns out to be more complicated. Studies of women with CAIS have found that many aspects of their brain structure and function are female-typical, consistent with the idea that androgen exposure shapes the brain. But some features were male-typical despite complete androgen resistance, hinting that sex chromosome genes themselves may directly influence brain development independent of hormones.20PubMed. The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes Research on animal models has reinforced this. XX and XY brain cells appear to behave differently even before gonads have formed and begun producing hormones, suggesting that the genetic sex of cells matters in its own right.21PubMed. Minireview: Sex chromosomes and brain sexual differentiation
This paints a picture of brain sexual differentiation as a multifactorial process, shaped by hormones, sex chromosome gene dosage, and possibly socialization. None of these factors alone tells the whole story, and the “default female brain” idea is even less defensible than the “default female body” version.22PubMed. Sex differences in brain and behavior: hormones versus genes
X-Chromosome Dosage and Early Epigenetics
One of the earliest molecular events that distinguishes XX from XY embryos has nothing to do with gonads or hormones. Female embryos carry two X chromosomes, and to prevent a double dose of X-linked genes compared to males (who have only one X), one X chromosome in each female cell is progressively silenced. This process, called X-chromosome inactivation, begins in the blastocyst stage, before implantation and long before any gonad has formed.23Scientific Reports. Early X chromosome inactivation during human preimplantation development revealed by single-cell RNA-sequencing The goal is dosage balance: making sure XX and XY cells express roughly the same amount of X-linked gene products.24PubMed Central. Modeling X-chromosome inactivation and reactivation during human development
This matters for the “are we all female” question because it shows that XX and XY embryos are already molecularly distinct well before the reproductive anatomy begins to diverge. The embryo is managing sex-chromosome dosage from its earliest cell divisions. At no point is an XY embryo operating with a “female” molecular profile. It has one X and one Y from the moment of fertilization, and epigenetic processes begin accommodating that reality almost immediately.
The Placenta Responds to Fetal Sex Too
The sex-specific biology of development extends beyond the embryo itself. The placenta, which is genetically identical to the fetus, also shows sex-dependent patterns. Research has found that high maternal glucocorticoid levels regulate a key placental enzyme in a sex-specific way, leading to measurable differences in placental and fetal development between male and female pregnancies.25PubMed. Differential expression of placental 11β-HSD2 induced by high maternal glucocorticoid exposure mediates sex differences in placental and fetal development Male and female placentas differ in gene expression, immune signaling, and responses to stress, and some of these differences emerge before the fetal gonads are even functional. The placenta is a reminder that the distinction between male and female biology is not just about reproductive organs; it runs through almost every tissue that has access to the genetic sex of the individual.
How Sex Determination Varies Across Species
Mammals are actually unusual in how rigidly their sex determination is locked to chromosomes. In many reptiles, the temperature at which eggs are incubated determines whether hatchlings develop as male or female, with no sex chromosomes involved at all. Amphibians and fish display an even wider range of mechanisms, including environmental triggers, hormonal cues, and social hierarchies. Compared to these groups, the mammalian XY system is remarkably stable and conserved.26PubMed. Are reptiles predisposed to temperature-dependent sex determination? That conservatism may explain why the “default female” model seemed so clean and universal when Jost proposed it: in mammals, removing the testicular signal reliably produces a female-appearing outcome. But applying the concept across the animal kingdom would make no sense, because many species have no equivalent of the SRY-driven switch.
Even within mammals, the gonad is not the whole story. Epigenetic signatures tied to mobile DNA elements begin to diverge between developing male and female gonads, suggesting another layer of regulation on top of the classical SRY-testosterone cascade.27bioRxiv. Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development Each new layer of complexity that researchers uncover makes the “default” framing look more like a historical artifact and less like an accurate description of what embryos are doing.