Bibliographic record
Abstract
Selection can generate risk of maladaptive extremes in sexually dimorphic and sex-limited traits.In humans, such extremes commonly manifest in diseases associated with sex and reproduction.Endometriosis involves endometrial tissue that proliferates at non-uterine sites.The proximate causes of endometriosis remain enigmatic, and its ultimate, evolutionary basis has only recently come under investigation.We propose and evaluate a new theory for helping to explain the evolution of endometriosis risk in humans.By this theory, endometriosis risk evolved in the context of sexual selection by males for high, relatively female-biased expression of sexually-dimorphic and female-limited phenotypes associated with high female reproductive fitness and low testosterone.The theory is supported by extensive data, from humans and non-human mammals, showing that: (1) endometriosis involves higher expression of major female-biasing genes, and lower expression of major male-biasing genes, that orchestrate prenatal sexual differentiation, including the genes Foxl2, Wnt4, Fst, Ctnnb1, Rspo1, Sox9 and Amh, (2) endometriosis and its correlates are associated with low prenatal and postnatal testosterone, both of which have female-biasing effects on traits, (3) low prenatal and postnatal testosterone, and endometriosis, are associated with relatively female-biased phenotypic expression for a large suite of sexually-dimorphic and sex-limited traits, (4) relatively female-biased expression of these traits is commonly associated with higher fertility and fecundity, (5) some traits, including female facial features, vocal pitch, and breast size, fit with all of the predictions of the model, though they have yet to be studied in relation to endometriosis, and (6) traits linked with low prenatal and postnatal testosterone (or high estradiol), and traits associated with endometriosis in humans, are preferred by males across multiple species of non-human mammals.Risk and symptoms of endometriosis thus appear to involve and represent, in part, maladaptive extremes of sexually selected female-limited and sexually-dimorphic traits.Such trait expression is mediated by genetic and environmental factors that bias development and physiology towards relatively low-testosterone and high-estradiol (as well as high-oxytocin) states.The hypothesis makes many testable predictions, and has direct implications for understanding the causes and treatment of endometriosis.(7) increased paternal care, which is expected to generate selective conditions favoring male choice of relatively fertile and fecund females (Hrdy, 2009);(8) the evolution of higher levels of monogamy and guarding of females by males (Schacht and Kramer, 2019), which can reinforce male choice and select for male choice of relatively-young females with high nubility and reproductive value (Lassek and Gaulin, 2019) who can be controlled and 'owned' by males for long periods of time (Hrdy, 1997) and ( 9) the recent evolution of reduced hair, eye and skin pigmentation in some populations, which influences availability and metabolism of the key reproductive nutrients vitamin D, folate, and calcium (Parra, 2007;Jablonski and Chaplin, 2017), and which generates new phenotypic and genetic substrates for sexual selection.A final factor important to the current prevalence of endometriosis is evolutionary mismatch, between adaptations to past environmental conditions, and environments that have changed too rapidly for selection and response to selection to track them.By this hypothesis, the current notably high prevalence of endometriosis in women, about 5-10%, is driven by recent secular trends towards earlier menarche and later age of first reproduction, both of which increase numbers of the menstrual cycles that increase the potential for retrograde flow and estrogenic stimulation of endometrial tissue growth.This hypothesis is consistent with epidemiological data linking endometriosis risk with correlates of numbers of menstruations (Scioscia et al., 2019), although directionalities of causality remain unclear because genes underlying endometriosis are also pleiotropically associated with earlier menarche (Ponomarenko et al., 2020).The presence of such mismatch would be expected to exacerbate, rather than generate de novo, the symptoms and severity of endometriosis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".