By JT Santana | jtwb768

There is a particular kind of absurdity that occurs when science “rediscovers” something that never actually disappeared.

The rete ovarii is one of those cases. It is a small epithelial structure associated with the ovary, described in scientific literature more than 150 years ago. Researchers knew it existed. Anatomists drew it. Comparative biologists found versions of it across mammalian species. Early editions of Gray’s Anatomy included it. Then it faded from mainstream anatomical attention and came to be described, when mentioned at all, as a vestigial structure with little apparent function (Anbarci et al., 2025; McKey et al., 2022). (PubMed)

That would be merely an interesting episode in the history of anatomy if it existed in isolation. It does not.

The history of medicine contains an uncomfortable pattern in which male anatomy has often functioned as the reference model, female physiology has been treated as troublesome variation, and unanswered questions about women have remained unanswered far longer than comparable questions about men. Women were excluded from major categories of clinical research. Female animals and cells were routinely left out of laboratory research. Anatomical textbooks gave less attention to female sexual anatomy than male sexual anatomy. Drug doses were developed under research systems that did not consistently examine whether medications behaved differently in female and male bodies.

Some of that history has changed. Women now account for roughly half of participants in NIH-supported clinical research, and federal research rules require investigators to address sex in many study designs. Yet participation alone does not settle the problem. Researchers still find gaps in sex-specific analysis, preclinical research has historically relied heavily on male animals and cells, and the FDA issued new draft guidance in December 2025 calling for better enrollment of female participants and better analysis of sex-specific data (FDA, 2025; NIH Office of Research on Women’s Health, 2025). (Orwh)

The rete ovarii deserves attention for more than its strange history. It forces an awkward question.

How does a structure sit next to one of the major reproductive organs, remain conserved across mammalian evolution, appear in anatomical literature for generations, and still reach the twenty-first century with scientists trying to establish its basic physiological role?

The answer is not that science is uniquely hostile to women or that generations of researchers consciously conspired to erase female anatomy. History is rarely that cartoonish. The record points to something more systemic: research priorities, assumptions about what counts as biologically significant, decisions about which questions deserve funding, fears surrounding pregnancy, inherited textbook conventions, and a scientific culture that spent generations treating male biology as the easier baseline.

The result is the same whether neglect was deliberate or institutional.

There are still parts of female biology for which medicine is catching up.

Meet the Rete Ovarii, the Structure Anatomy Misplaced

The rete ovarii is not a new discovery.

Wilhelm von Waldeyer described it in 1870. Researchers later identified it as a possible female counterpart to the rete testis, the network of channels associated with the male reproductive system. Modern developmental research divides the rete ovarii into three regions: the intraovarian rete inside the ovary, the extraovarian rete outside it, and a connecting region linking those components (McKey et al., 2022). (PubMed Central (PMC))

That makes the history especially curious. Scientists did not lose a microscopic speck that appeared once in an obscure nineteenth-century paper. The structure persisted across mammalian species and had been discussed repeatedly in the literature. A 1985 review of the mammalian rete ovarii had already argued against treating the adult structure as a meaningless leftover, citing evidence suggesting secretory activity and possible roles in ovarian development (Wenzel & Odend’hal, 1985). (PubMed)

Yet the rete ovarii receded from modern descriptions of female reproductive anatomy. Researchers behind the recent work explicitly observed that it appeared in early editions of Gray’s Anatomy before disappearing from newer textbooks (Anbarci et al., 2025). (PubMed Central (PMC))

Then researchers at Duke University and collaborating institutions began examining it again using contemporary developmental biology.

Their findings are fascinating. In mouse ovaries, the extraovarian portion forms a complex tubular structure. Its cells are ciliated and display cellular trafficking activity. Researchers injected material into the structure and observed luminal contents moving in the direction of the ovary. Mass spectrometry detected secreted proteins that could influence ovarian physiology. Researchers found close relationships between the structure and blood vessels, macrophages, and neuronal projections (Anbarci et al., 2025). (PubMed)

That is a considerable amount of biological activity for something once dismissed as a vestige.

There is one distinction that needs to be made clearly, particularly given how this story has circulated online. The experimental work establishing these functions was performed in mice. It did not demonstrate that the human rete ovarii performs every identified mouse function, nor did researchers suddenly discover a previously unknown human organ. The human structure had already been documented, and the rete ovarii has been described across many mammalian species (Anbarci et al., 2025). (PubMed Central (PMC))

That correction does not weaken the larger story. It makes it more interesting.

Scientists have known about the structure for approximately a century and a half. Its possible significance had been raised decades ago. Modern experimental techniques are now supplying evidence that it may participate in ovarian development, homeostasis, secretion, and communication with surrounding tissues. An eLife commentary accompanying the 2025 research suggested that the rete ovarii may have relevance to follicular dynamics and reproductive health, though substantial work remains before its physiological roles are established (Zhang & Zhang, 2025). (eLife)

The scandal, if we want to use that word, is not that scientists discovered a secret female organ in 2025.

It is that there was still so much basic biology left to investigate.

Science Had a Default Human, and He Was Usually Male

The rete ovarii fits inside a much larger historical problem.

For generations, biomedical researchers often treated male organisms as cleaner experimental subjects. Female hormonal cycles were characterized as sources of variability. Pregnancy introduced ethical and liability concerns. Researchers seeking tidy datasets could avoid both complications by studying males and assuming the resulting knowledge would transfer adequately to females.

That assumption became embedded across the research pipeline.

The National Institutes of Health now acknowledges the history directly. NIH states that basic and preclinical biomedical research frequently focused on male animals and cells and that excessive reliance on male research subjects can obscure biologically meaningful sex differences (NIH Office of Research on Women’s Health, 2025). (Orwh)

Humans were affected by a similar logic.

Following concerns about fetal harm associated with medications such as thalidomide, the FDA issued guidance in 1977 recommending that women of childbearing potential be excluded from Phase I and early Phase II drug trials. The restriction was broad. Women could be excluded despite using contraception, being unmarried, or having partners who had undergone vasectomy (NIH Office of Research on Women’s Health, n.d.). (Orwh)

Protecting potential pregnancies became a justification for denying many women the opportunity to decide whether to participate in research.

There was a cruel scientific tradeoff hidden inside that policy. Keeping women out of early drug research reduced one category of theoretical reproductive risk, yet it created another risk: physicians and regulators had less evidence about what those drugs did inside women who would later receive them.

Women’s health advocates challenged that arrangement. HIV/AIDS activists raised the issue when women were excluded from experimental drug trials during an epidemic in which access to emerging therapies could mean survival. The federal government began changing course during the 1980s, and NIH established policies encouraging women’s inclusion in research (NIH Office of Research on Women’s Health, n.d.). (Orwh)

Those early policies were not enough.

A Government Accountability Office investigation found that NIH had poorly communicated its inclusion policy, applied it inconsistently, and done little to require meaningful analysis of results by sex. Congress responded through the NIH Revitalization Act of 1993, which made inclusion of women and racial and ethnic minority groups a statutory requirement in NIH-funded clinical research under defined conditions (NIH, 1994). (Grants.gov)

Consider the timeline.

The rete ovarii was described in 1870.

The United States did not put a statutory requirement for women’s inclusion in NIH-funded clinical research into place until 1993.

NIH did not implement its policy expecting researchers to account systematically for sex as a biological variable across eligible vertebrate animal and human research until 2016 (Clayton, 2020). (PubMed)

These are not ancient scientific practices we inherited from physicians working by candlelight. Many people alive today were adults before federal biomedical research policy seriously confronted some of these gaps.

The Medicine Cabinet Carries This History Too

It would be easier to treat all of this as academic housekeeping if the consequences stayed inside anatomy textbooks and research laboratories.

They did not.

Sex can influence how medications are absorbed, distributed, metabolized, and eliminated. Hormones, body composition, enzyme activity, kidney function, and other physiological variables can influence pharmacokinetics and pharmacodynamics. None of this means every medication requires different treatment according to sex. It means assuming identical behavior without testing the assumption is poor science.

One of the clearest examples involved zolpidem, better known through the brand name Ambien.

The FDA found that women cleared zolpidem more slowly than men on average. At equivalent doses, women had approximately 45 percent higher peak concentrations and overall drug exposure in data reflected in FDA labeling. Concern centered on next-morning impairment, including impairment affecting driving and other activities requiring alertness. In 2013, FDA labeling recommended a lower initial dose for adult women: 5 mg rather than the previous 10 mg immediate-release dose (FDA, 2013). (FDA Access Data)

One medication does not prove that all women have been systematically overdosed. Zolpidem itself has generated continued academic debate over the interpretation and policy significance of observed sex differences. Still, the episode illustrates why sex-specific pharmacological research cannot be treated as decorative information.

The broader medication record is more troubling.

A 2001 GAO examination identified ten prescription drugs withdrawn from the U.S. market beginning in 1997. Eight presented greater health risks for women than men. For four drugs, greater female harm appeared connected to higher prescribing rates among women. Four others produced more adverse events among women despite widespread use among both sexes (U.S. Government Accountability Office, 2001). (U.S. Government Accountability Office)

That distinction deserves attention. It would be inaccurate to claim all eight drugs harmed women more solely as a result of their exclusion from clinical trials. Prescription patterns, underlying conditions, pharmacology, and other variables matter. The GAO findings still demonstrate why postmarket safety cannot be treated as sex-neutral by default.

A 2020 analysis examining 86 drugs with identified pharmacokinetic sex differences found that women often had higher blood concentrations and longer elimination times. Among drugs with identifiable adverse reactions, the direction of pharmacokinetic differences strongly corresponded with female-biased adverse reactions in many cases (Zucker & Prendergast, 2020). (PubMed Central (PMC))

Even that widely cited research requires context. A 2023 study using FDA adverse-event reporting data found that the frequently repeated claim that women experience drug adverse events at one-and-a-half to twice the rate of men becomes far less dramatic after researchers account for different rates of medication use. The authors found that adjusting for drug utilization substantially narrowed the apparent gap (Watson et al., 2023). (JAMA Network)

That is exactly how this subject should be discussed.

Evidence should sharpen criticism, not serve as decoration for it.

There is no need to inflate the case against historical sex bias in medicine. The documented record is serious enough.

Then There Is the Clitoris

Few examples capture the strange history of female anatomy more effectively than the clitoris.

A familiar claim states that medicine did not discover or accurately map the complete clitoris until 1998. The reality is more complicated. Detailed clitoral anatomy had been described much earlier, including nineteenth-century anatomical work. Australian urologist Helen O’Connell and colleagues published influential modern research in 1998 clarifying relationships among the clitoris, urethra, and surrounding structures, followed by later imaging and anatomical work that challenged incomplete textbook representations (O’Connell et al., 1998; O’Connell et al., 2005). (PubMed)

So no, the clitoris did not suddenly materialize in a laboratory in 1998.

The more defensible criticism is arguably worse.

Accurate knowledge existed, yet educational representations often remained inadequate. A 2014 analysis of anatomy teaching noted that modern textbooks frequently provided reduced descriptions of female perineal anatomy. The authors cited earlier research finding that several anatomy textbooks published between 1950 and 1971 either omitted the clitoris or depicted something resembling it without labeling it (Morgan et al., 2014). (PubMed Central (PMC))

Researchers disagree over how much of that omission can legitimately be attributed to deliberate sexism. A 2022 critique argued that influential historical analyses of textbook treatment of the clitoris used methods that were difficult to reproduce and sometimes overstated their conclusions (Vilensky et al., 2022). (PubMed)

That disagreement belongs in the story.

Sex bias in medicine is a serious research subject, not a slogan requiring every disputed historical claim to be accepted. The strongest case comes from distinguishing what can be demonstrated from what has become folklore.

What can be demonstrated is that female sexual anatomy has repeatedly received less complete textbook treatment than male sexual anatomy. Researchers have documented inaccuracies and omissions. O’Connell’s work showed that standard textbook descriptions lacked anatomical detail available through dissection and modern imaging. Research published far more recently continues finding incomplete educational representation of the clitoris in some science textbooks (Tavares et al., 2025). (PubMed)

The issue is not whether anatomy books contained the word clitoris.

The question is what students were actually being taught to understand.

Inclusion Improved. The Knowledge Gap Did Not Vanish.

It would be equally dishonest to write as though biomedical science has learned nothing from its history.

Women now represent roughly half of participants in NIH-supported clinical research. NIH-funded research is governed by inclusion requirements, and researchers proposing many single-sex studies must provide scientific justification. Since 2016, NIH has expected investigators conducting eligible vertebrate animal and human studies to consider sex in research design, analysis, and reporting (NIH Office of Research on Women’s Health, 2025). (Orwh)

The FDA has an Office of Women’s Health. Regulators explicitly recognize that biological sex can influence the safety and effectiveness of drugs, biologics, and medical devices. Clinical research standards now bear little resemblance to the blanket exclusion policy of 1977 (FDA, n.d.). (U.S. Food and Drug Administration)

Yet aggregate participation figures can hide more specific problems.

Women may constitute approximately half of all participants across a large research portfolio and still be underrepresented in particular diseases, specialties, trial phases, or therapeutic areas. A study examining pivotal trials supporting FDA-approved cancer therapies found that women comprised 40.7 percent of participants in the non-sex-specific cancer trials examined and were underrepresented relative to disease incidence in 66.9 percent of those trials. Sex-specific safety data were reported in only 4 percent of the trials assessed (Ludmir et al., 2024). (PubMed Central (PMC))

Enrollment is one layer.

Analysis is another.

A study can recruit women and still lack enough participants to detect meaningful sex differences. Researchers can collect the data and fail to report outcomes separately. Trials can enroll representative populations yet leave pregnant people almost entirely outside the evidence base. Preclinical research can contain both male and female animals without being statistically structured to test sex-related effects.

These are methodological problems, not culture-war abstractions.

The FDA’s December 2025 draft guidance on studying sex differences makes that point through its very existence. The agency recommended increasing enrollment of female participants where needed, analyzing sex-specific information, interpreting that information appropriately, and incorporating relevant findings into regulatory submissions (FDA, 2025). (U.S. Food and Drug Administration)

A research problem considered fully solved does not usually require fresh federal guidance telling investigators how to solve it.

What the Rete Ovarii Story Actually Tells Us

The temptation with stories like this is to turn them into easy outrage.

“Scientists ignored women.”

There is truth inside that sentence, yet it is too blunt to explain what happened.

Science is not one person making one decision. It is a network of institutions, funding systems, laboratories, journals, professional traditions, regulatory agencies, ethical standards, educational materials, and inherited assumptions. Bias can enter through any of them. Once it becomes embedded in research convention, nobody needs to announce that female biology is less worthy of study. Researchers merely keep asking the questions their fields already consider important.

That is how scientific blind spots survive.

The rete ovarii appears to be a superb example. It was described in the nineteenth century. Researchers revisited it intermittently. Comparative anatomists documented it in numerous mammals. Earlier scientists proposed possible developmental and secretory functions. Yet it remained marginal enough that twenty-first-century developmental biologists could reasonably characterize their work as “rediscovering” it (Anbarci et al., 2025). (eLife)

There is a lesson here that extends past sex and reproductive anatomy.

What scientists choose to measure affects what medicine can know.

What medical schools choose to teach affects what clinicians recognize.

What clinical trials choose to analyze affects what regulators can place on a drug label.

What researchers classify as insignificant may determine whether another generation ever asks what a structure actually does.

None of that requires believing science is corrupt. Quite the opposite. Science improves through criticism, replication, correction, and the willingness to revisit assumptions that previous researchers treated as settled.

The new rete ovarii research is science correcting science.

That deserves celebration.

The fact that correction was needed deserves scrutiny.

We Should Be Careful With the Outrage — and Keep the Outrage

The original version of this story circulating online contains a few flourishes that are irresistible. Guinea pigs receive better reproductive-anatomy attention than women. Male anatomy gets mapped down to the plumbing, female anatomy gets tossed into the scientific junk drawer. Somebody inevitably mentions a researcher with spectacular eighteenth-century hair.

It makes for great copy.

It also risks turning a powerful indictment of research bias into something critics can dismiss by identifying one overstated fact.

The rete ovarii was not newly discovered in women last year. The major 2025 functional study examined mice. The structure’s function in humans remains insufficiently established. Its relationship to the rete testis is more complicated than calling the two structures identical. The clitoris was not literally unknown to anatomists until 1998. Women today are not universally absent from clinical trials.

All true.

Now look at what remains after correcting every one of those claims.

A structure associated with the ovary was documented in 1870 and later disappeared from many modern anatomical descriptions. Researchers in 2025 reported convincing experimental evidence that this supposedly unimportant structure performs complex biological activities in mice. Scientists still need to determine the extent to which those functions translate to humans.

Women were broadly excluded from early-stage drug trials under a 1977 FDA policy. Congress did not establish statutory NIH inclusion requirements until 1993. NIH implemented its major sex-as-a-biological-variable policy in 2016. Federal agencies continue issuing guidance aimed at improving female representation and sex-specific analysis.

Textbooks have historically provided incomplete descriptions of female sexual anatomy. Pharmacological research has demonstrated clinically meaningful sex differences for some drugs. Cancer trials and other research areas continue showing gaps in female representation or sex-specific reporting.

The corrected story is still damning.

Perhaps more damning.

Sensationalism gives institutions an escape hatch. Precision closes it.

Female Biology Was Never the Complication

One phrase appears repeatedly when reading the history of women in biomedical research: female physiology was considered too complicated.

Hormonal cycles were complicated.

Pregnancy was complicated.

Reproduction was complicated.

Differences in metabolism were complicated.

Recruiting representative populations was complicated.

Analyzing results separately was complicated.

That language reveals the deeper scientific failure.

Women were not unusually complicated. Human biology was complicated.

Researchers had simply become accustomed to treating one portion of humanity as the baseline and everything that departed from it as inconvenient variation.

The entire purpose of biomedical research is to investigate variation. Age changes physiology. Genetics changes physiology. Kidney function changes drug metabolism. Race and ethnicity can correlate with environmental, socioeconomic, genetic, and health-care variables requiring careful study rather than crude biological assumptions. Pregnancy radically changes physiology. Hormonal states matter. So does body composition. So do dozens of variables researchers routinely accept as part of studying human beings.

Calling female physiology inconvenient never made it scientifically irrelevant.

It made the research easier.

Patients paid for that convenience.

The rete ovarii is tiny compared with the history surrounding it. Most people will never hear its name. It may eventually prove central to some aspects of ovarian biology, or its human role may turn out to be more limited than current animal studies suggest. That question belongs to future research.

Its symbolic value already exists.

It sat there for generations.

In drawings. In tissue. In animals. In humans. In old literature. In the margins of newer literature.

The rete ovarii did not disappear.

Our attention did.

Medicine has spent the last several decades repairing some of the consequences of treating male biology as the default template. That repair has produced stronger inclusion rules, better attention to sex-specific pharmacology, more representative clinical research, improved anatomical descriptions, and a growing recognition that experimental convenience is not the same thing as biological truth.

The work is unfinished.

The next time somebody says scientists have “rediscovered” another part of female anatomy, the first question should not be, How could nobody have known this existed?

A better question is far more uncomfortable:

Who knew, when did they know it, and why did medicine decide it was not worth knowing more?

That is where the real story usually begins.

References

• Anbarci, D. N., McKey, J., Levic, D. S., Bagnat, M., & Capel, B. (2025). Rediscovering the rete ovarii, a secreting auxiliary structure to the ovary. eLife, 13, RP96662. https://doi.org/10.7554/eLife.96662
• Clayton, J. A. (2020). Sex as a biological variable: A 5-year progress report and call to action. Journal of Women’s Health, 29(6), 858–864.
• Food and Drug Administration. (2013). Ambien prescribing information: Gender difference in pharmacokinetics. U.S. Department of Health and Human Services.
• Food and Drug Administration. (2025). Study of sex differences in the clinical evaluation of medical products: Draft guidance for industry. U.S. Department of Health and Human Services.
• McKey, J., et al. (2022). Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii. eLife, 11, e81088.
• National Institutes of Health. (1994). NIH guidelines on the inclusion of women and minorities as subjects in clinical research. NIH Guide, 23(11).
• National Institutes of Health Office of Research on Women’s Health. (2025). Sex as a biological variable. National Institutes of Health.
• O’Connell, H. E., Hutson, J. M., Anderson, C. R., & Plenter, R. J. (1998). Anatomical relationship between urethra and clitoris. The Journal of Urology, 159(6), 1892–1897. https://doi.org/10.1016/S0022-5347(01)63188-4
• O’Connell, H. E., Sanjeevan, K. V., & Hutson, J. M. (2005). Anatomy of the clitoris. The Journal of Urology, 174(4), 1189–1195.
• U.S. Government Accountability Office. (2001). Drug safety: Most drugs withdrawn in recent years had greater health risks for women (GAO-01-286R).
• Wenzel, J. G. W., & Odend’hal, S. (1985). The mammalian rete ovarii: A literature review. Cornell Veterinarian, 75, 411–425.
• Zhang, Y., & Zhang, H. (2025). Revisiting the rete ovarii. eLife, 14, e106648.
• Zucker, I., & Prendergast, B. J. (2020). Sex differences in pharmacokinetics predict adverse drug reactions in women. Biology of Sex Differences, 11, 32. https://doi.org/10.1186/s13293-020-00308-5