Description

Many people claim that all embryos begin as females. Is this true? And what does the science of embryology have to say about it?

Sources

Biason-Lauber, A. (2012). WNT4, RSPO1, and FOXL2 in sex development. Seminars in Reproductive Medicine, 30(5).

DiNapoli, L., Capel, B. (2008). SRY and the standoff in sex determination. Molecular Endocrinology, 22(1).

Eggers, S., Sinclair, A. (2012). Mammalian sex determination—insights from humans and mice. Chromosome Res, 20:215-238.

Gershoni, M., et al. (2017). The landscape of sex-differential transcriptome and its consequent action in human adults. BMC Biology, 15(7).

Kim, Y., Kobayashi, A., Sekido, R., et al. (2006). FGF9 and WNT4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biology, 4(6).

Mullen, R., Behringer, R. (2015). Molecular genetics of Mullerian duct formation, regression, and differentiation. Sex Dev, 8(5), 281-296.

Ottolenghi, C., Pelosi, E., Tran. J., et al. (2007). Loss of WNT4 and FOXL2 leads to female-to-male sex reversal extending to germ cells. Human Molecular Genetics, 16(23), 2795-2804.

Prunskaite-Hyyryläinen, R., Skovorodkin, I., Xu, Q., et al. (2016). WNT4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract. Human Molecular Genetics, 25(6).

Rey, R., Josso, N., Racine, C. (2020). Sexual differentiation. In: Endotext. South Dartmouth, MDText, Inc.

Warr, N., et al. (2012). The molecular and cellular basis of gonadal sex reversal in mice and humans. WIREs Dev Bio, 1.

Wilson, D., Bordoni, B. (2023). Embryology, Mullerian ducts (paramesonephric ducts). In: StatPearls [Internet]. Treasure Island (FL): Stat Pearls Publishing.

Wolpert, L., Tickle, C., & Martinez Arias, A. (2019). Principles of Development (6th ed.). Oxford University Press.

Zhao, F., Franco, H., Rodriguez, K., et al. (2017). Elimination of the male reproductive tract in the female embryo is actively promoted by COUP-TFII. Science, 357(6352), 717-720.

Zhao, F., Yao, H. (2019). A tale of two tracts: history, current advances, and future directions of research on sexual differentiation of reproductive tracts. Biology of Reproduction, 101(3).

Transcript

In the 1993 movie, Jurassic Park, while huddled around a baby velociraptor hatching out of its egg, scientist Henry Wu explains to the group that all vertebrate embryos begin as female, and that an extra hormone, given at the right developmental stage, turns them into males. To make them all female, he says, we just deprive them of that extra hormone. However, modern embryology has shown this to be a myth. Let’s explore why.

The Indifferent Stage

As young embryos, vertebrates begin undifferentiated (Wolpert, Tickle, & Arias 2019).

Our gonads at this stage are bipotential: they have the capability to differentiate into either testes or ovaries (Rey et al. 2020). For us mammals, this is decided by what sex chromosomes we inherit at conception (XX or XY) and the genes inside them. Barring genetic disorders, XX will result in ovaries. XY will result in testes.

Our genitals are also bipotential: we have the primitive genital ducts for both sexes, known as the Mullerian and Wolffian ducts (Rey et al. 2020). Mullerian ducts become the female genital system. Wolffian ducts become the male genital system. During sex development, one duct will be eliminated while the other one will be differentiated, so that both sexes end up with just one set of genital ducts.

Therefore, the claim that “all fetuses begin as female” can only be true if undifferentiated gonads and undifferentiated genitalia are equivalent to being female. But being female involves a specific path of development: the gonads differentiating into ovaries, and the Mullerian duct differentiating into the oviducts, uterus, and vagina for mammals. Female development does not mean undifferentiated. For us all to begin as female on a physical level, we would have to develop ovaries and female genitalia first. Then to make a male, ovaries would transform into testes. And the female genitalia would transform into male genitalia. But this is not what happens. Instead, our reproductive system begins in a bipotential state, and then we differentiate along either the male or female pathway.

But where did this “we all begin female” myth come from? Some might say Jurassic Park, but it’s actually much older than this.

The Jost Experiments

In the middle of the 20th century, French endocrinologist Alfred Jost took rabbit embryos and removed their gonads before sex differentiation began. He discovered that the embryos with no gonads, regardless of whether they had XX or XY chromosomes, developed the Mullerian ducts of oviducts, uterus, and vagina (the female genitalia). He then grafted testes to an XX embryo and saw that the fetus developed the Wolffian ducts (the male genitalia) and no female genitalia. From his experiments on rabbits, Jost concluded that the development of female genitalia was a default process, whereas development of the male genitalia was an additive process from the sex hormones produced by the testes (Zhao & Yao 2019; DiNapoli & Capel 2008). This is where Jost’s observations transformed into a tangled myth. What was originally the correct claim of “the female genitalia develop in the absence of any gonad” became the incorrect claim of “we all start as females” or that “female is a passive pathway.”

However, since then, genetic studies have discovered two missing pieces from Jost’s experiments. The first missing piece was found in the development of the gonads, the most crucial step of sex development. Many studies have revealed that the development of ovaries, like the development of testes, is an active genetic process (Biason-Lauber 2012).

For example, in XY embryos, loss of genes for testes development usually results in undifferentiated gonadal tissue called streak gonads, not ovaries.

Likewise, in XX embryos, loss of essential X-linked genes for ovaries can also result in streak gonads.

Finally, in XX embryos, loss of WNT4 and FOXL2 can lead to testes development, instead of ovaries. These two genes are crucial for upregulating the ovarian pathway and for suppressing testes development (Ottolenghi, Pelosi, Tran, et al. 2007; Kim, Kobayashi, Sekido et al. 2006; Eggers & Sinclair 2012).

From these findings, geneticists concluded that, “It is clear that initiation of the ovarian pathway involves the active regulation of many genes and is not simply a passive / default developmental process” (DiNapoli & Capel 2008).

The second missing piece was found in the genitalia (the Mullerian and Wolffian ducts). Studies on mice and humans have shown that correct differentiation of the Mullerian duct requires WNT and HOX gene networks, not just absence of male sex hormones. Without these genetic networks, female fetuses failed to develop complete Mullerian ducts (Mullen & Behringer 2015; Prunskaite-Hyyryläinen et al. 2016; Wilson & Bordoni 2023).

Once the genetics behind the Mullerian duct formation were discovered, focus shifted to the genetics of the Wolffian duct. A 2017 study on mice revealed that the Wolffian duct in females, thought to be eliminated in the absence of testosterone, actually needs active suppression by the COUP-TFII gene pathway. Thus, females missing this signaling will retain and develop the Wolffian ducts despite lack of testosterone (Zhao, Franco, & Rodriguez et al 2017).

This groundbreaking research provided important insight missing in Jost’s experiments, challenging the oversimplified model. As it turns out, both sexes require active genetic networks to fully develop the gonads and genitalia, upregulating one path and suppressing the other (Warr et al. 2012).

Despite all this evidence, the myths still persist. Since the conclusions of Jost’s experiments have been exaggerated, many people now falsely believe that we all start as female, that females are underdeveloped males, and that the only difference between the sexes is testosterone levels. This has broad implications.

First, the myth we all start as female muddies biology education, sowing confusion and ignorance. For example, a 1970s paper in the Journal of Sex and Marital Therapy called “Some Biology of Sexuality” claims that “geneticists have discovered that all human embryos start life as females.” And a 2001 book called “Exploring the Biological Contributions to Human Health” published by the National Acadamies claims that “all fetal genitalia are the same and are phenotypically female.” These two examples are often used by the public and educators.

Second, the false implication that females are underdeveloped males could reinforce harmful sex stereotypes—that female traits are less evolved or secondary. This can damage how society views the capabilities, roles, and rights of females.

Finally, the belief that testosterone is the only difference between male and female ignores the different genetics between the sexes and the differences in gene expression that arise. Researchers have found over 6500 genes that express themselves differently between males and females (Gershoni et al. 2017). Ignoring these genetics could skew hypotheses and misdirect research into how sex differences in disease manifest. This could negatively impact the effectiveness of sex-specific therapies and the development of drug treatments.

Despite what the scientists in Jurassic Park claim, we do not all start female. Both sexes begin physically indifferent, before our genetics differentiate us down either the male or female path. And developing as a female, like developing as a male, is a specific path of differentiation, with all the important differences that arise from this specialized pathway.

© 2025 Zachary A. Elliott, All Rights Reserved.