Weapon Grave at Suontaka Vesitorninmäki, Finland

In 1968, a weapon grave with brooches was found at Suontaka Vesitorninmäki, Hattula, Finland. Since then, the grave has been interpreted as evidence of powerful women, even female warriors and leaders in early medieval Finland. Others have denied the possibility of a woman buried with a sword and tried to explain it as a double burial. We present the first modern analysis of the grave, including an examination of its context, a soil sample analysis for microremains, and an aDNA analysis. Based on these analyses, we suggest a new interpretation: the Suontaka grave possibly belonged to an individual with sex-chromosomal aneuploidy XXY. The overall context of the grave indicates that it was a respected person whose gender identity may well have been non-binary.

There is an enduring fascination with women buried with weapons, but the topic continues to be debated. A specific Finnish find, an early medieval inhumation grave dated to (ad 1050–1300) found at Suontaka Vesitorninmäki in the municipality of Hattula (formerly Tyrväntö) (see above), has often been interpreted as a woman buried with two swords. The interpretation is based on dress accessories and jewellery, which suggest that the individual was dressed in feminine clothes. For decades, the grave has been a popular example of powerful women in Late Iron Age and early medieval societies. At the National Museum of Finland’s permanent exhibition between 1995 and 2016, the grave was used as evidence of female leaders in the past. In popular discussions and contexts, for example history forums on the internet, international sword replica shops, and even in the controversial ‘Meet the Viking’ exhibition at the National Museum of Denmark, the decorated bronze-hilted sword allegedly found in the Suontaka burial is presented as a female warrior’s weapon.

In this article, we present the first detailed study of the Suontaka grave. We undertook a careful analysis of the original field documentation to determine whether the grave had initially been a double burial, and to provide clarification on its context. To investigate the grave’s original context in detail, we conducted a study of microscopic animal hair and fibre remains from the soil retrieved from the grave. Lastly, we studied ancient DNA (aDNA) from the skeletal remains to infer the chromosomal sex of the individual. We conclude the article by drawing the results of these analyses together and discuss their possible meaning in the framework of gender archaeology.

As bone material from the Suontaka grave consists of only two highly degraded femur fragments, an osteological analysis could not be carried out. Ancient DNA (aDNA) analyses, on the other hand, may be used to infer the chromosomal sex of an individual even from low quantities of skeletal material. We extracted and sequenced aDNA from one of the femur fragments in the archaeogenetics laboratory of the Max Planck Institute for the Science of Human History in Jena, Germany. Unfortunately, the sample gave a very low yield of endogenous human DNA: even after a capture procedure to enrich for human DNA, the data contained only 106,781 sequence reads mapping to the human genome (of a total of 18,250,176 overall reads), 8329 of which had a mapping quality above 30. Of these, 2534 also showed post-mortem damage (PMD) scores above 0 from PMDtools (Skoglund et al. This paucity of data seriously limited the range of aDNA analyses that could be conducted, including those for data authentication. Therefore, we did not extend our genetic analyses beyond sex determination, as that is among the analysis types that need the least amount of data.

A: plan of the Suontaka burial. ‘Täckdike’ marks the water pipe trench which led to the discovery of the grave. B: artist’s reconstruction of the burial, showing the position of the objects on the body. A reproduced by permission of Finnish Heritage Agency. B: drawing by Veronika Paschenko.

Existing methods for chromosomal sex determination lack power for data as sparse as this, but their results suggested that the Suontaka individual’s X-chromosomal and Y-chromosomal read counts fit neither those expected for XX (female) nor for XY (male) individuals. We therefore developed a novel approach to estimate the chromosomal sex of the individual, where we down sampled sequencing reads from individuals of known genetic sex to the number of reads observed in the Suontaka individual (n = 8329) to model four possible scenarios that could have produced the observed data: XX, XY, a contaminated sample with a mix of reads from XX and XY individuals, and an aneuploidic karyotype XXY (male with Klinefelter syndrome).

Despite the extremely low sequencing coverage, we found overwhelming evidence that the genetic data of the Suontaka individual most closely resemble an XXY karyotype: our model classified the Suontaka individual as XXY at a 99.75 per cent probability, as contaminated with a 0.25 per cent probability, and as XX or XY with a very low probability (less than 10-6 in either case). In a subset of data that was enriched for plausibly ancient-looking reads (n = 2534), the corresponding probabilities were 99.96 per cent for XXY, 0.04 per cent for contamination, and again negligible for XX and XY; it therefore seems that the XXY signal in the data is not driven by potential modern contaminating DNA. Even when we take into account the low population frequency of the XXY karyotype, the XX and XY scenarios remain extremely unlikely, and—unless we assume a considerably high prior probability of contamination—the Suontaka individual’s karyotype is still most likely to be XXY.

The condition in which males are born with one or more extra X chromosomes is known as Klinefelter syndrome. With its prevalence of 1 in 576 male births, XXY is the most common sex-chromosomal aneuploidy in humans. The clinical signs of karyotype XXY vary from very subtle and unnoticeable to apparent differences in physical features. The anatomical appearance of XXY individuals is male, and some of them never even notice that they have the condition. In some cases, the clinical signs are stronger: XXY males can be infertile and have hypospadias (the opening of the urethra is on the underside of the penis), small phallus and testicles, and gynecomastia (breast growth). Testosterone deficiency may cause delayed or incomplete pubertal development. Sometimes effects on physical and cognitive development are reported and, according to some studies, modern XXY males may consider themselves more sensitive and unassertive than others . Interviews also suggest gender-related insecurities stemming from the XXY males feeling physically more feminine than other mal. Because the modern XXY males may compare their experiences to modern expectations of sex and gender, it is difficult to say how the physical and possibly psychological aspects would have been understood and displayed in eleventh–twelfth-century Finland.

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Exogenous Testosterone is not a requirement of 47XXY’s at Mini and Pre‑Puberty

The hypothalamus–pituitary–gonadal axis (HPG) during mini-puberty in boys with KS has been evaluated by several investigative groups and “all” possible results recorded: above normal, below normal or indistinguishable from normal (Aksglaede, Petersen, Main, Skakkebæk, & Juul, 2007; Lahlou, Fennoy, Ross, Bouvatier, & Roger, 2011; Ross et al., 2005). None of these studies has enough boys evaluated at various times over the course of mini-puberty and very few studied longitudinally. That has led to variable prescription of T for infant boys with KS. Davis et al. have noted that T secretion during mini-puberty leads to sexually dimorphic changes in linear growth, genital growth, and anabolic changes in body composition. Her group has further studied those with KS by administering 3 monthly doses of T, 25 mg each. The results compared to boys with KS who did not receive T indicate lesser increase in fat mass and greater increase in fat free mass and linear growth (Davis, Reynolds, Dabelea, Zeitler, & Tartaglia, 2019). One cannot determine from these data whether one is replacing subnormal amounts of T or using T as a pharmacological agent

Rogol, A. D. (2020). Human sex chromosome aneuploidies: The hypothalamic–pituitary–gonadal axis. American Journal of Medical Genetics Part C: Seminars in Medical Genetics

Klinefelter syndrome (XXY), first described by Harry Klinefelter in 1942, is the most common sex-chromosomal variation, with a prevalence of 1:660 in the general population. It is caused by the presence of an extra X chromosome (80% karyotype 47, XXY; 20% 46, XY/47, XXY mosaicism or structural X chromosome variations). It is also one of the most frequent causes of infertility, affecting 11% of azoospermic and 3.1% of all infertile males

The prevalence of diagnosed XXY has risen in recent decades, but its true prevalence is still thought to be underestimated, probably due to the extreme variability of its clinical presentation and a lack of awareness among general practitioners. Abramsky and Chapple showed that up to 64% of KS patients are never diagnosed, with 10% diagnosed prenatally and only 26% in prepuberty or adulthood.

47, XXY males may present with a variety of subtle, age related clinical signs. Hypospadias, small phallus, cryptorchidism, developmental delay, behavioral problems, incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes are its most frequent features in infancy and childhood. Adults are often evaluated for infertility and sexual disorders, but metabolic syndrome, osteoporosis, thyroid dysfunctions, humoral immunoreactivity and the presence of specific personality traits and personality disorders are also described. As regards fertility aspects, it has been recently stated that Y chromosome micro-deletions do not represent a further negative genetic factor in KS.

The function of the hypothalamus–pituitary–gonadal (HPG) axis in KS subjects has already been investigated, especially in relation to mini-puberty and puberty. Mini-puberty has been investigated extensively, as it is an important temporal window lasting from the first to about the sixth-to-ninth month of life, in which the first significant HPG axis activation takes place. There is literature evidence of prenatal tubular damage, but these results were not confirmed in childhood biopsies of boys with non-mosaic KS. In 2011, Aksglaede reported that testicular damage begins at the age of 4–9 years with a gradual degeneration of germ cells and reaches its peak from mid-puberty to adulthood, by which time the testes have undergone extensive seminiferous tubule hyalinization and Leydig and Sertoli cell hyperplasia. Literature studies agree that mini-puberty in KS boys is similar to that in healthy boys. However, there is no consensus on the hormonal and clinical profile of young KS patients, nor on when testicular damage occurs.

The aim of this study was therefore to accurately establish the testicular function and the main auxological features over a longer time period, from mini-puberty to the onset of puberty, in order to find any auxological and/or hormonal changes that might be used as an early indicator of KS. This broader clinical and hormonal follow-up might also clarify the specific timing of the onset of puberty, given that while most KS patients present a normal puberty, in some it is delayed and in even more it is precocious

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Diagnosing Sex Chromatin: A Binary for Every Cell

In 1949, Canadian anatomist Murray Barr announced the discovery of a peculiar entity in the cell nucleus that was present in females and absent in males. The identity of this entity remained uncertain for a decade even though Barr hypothesised a relationship between it and the sex chromosomes and called it the ‘‘sex chromatin.’’ This hypothesis inspired the development of the chromatin into a technology that could indicate ‘‘chromosomal’’ or ‘‘genetic’’ sex, which supposedly established male and female sex difference as a binary and fundamental characteristic of humans and other animals at conception. Barr collaborated with other researchers and potential patients who applied the sex chromatin test, hoping that it could identify the ‘‘true’’ sex of intersexuals, homosexuals, and transsexuals. Ironically, the application of the test to intersexuals would lead to a revision of the identity of the sex chromatin itself. The history of the sex chromatin illuminates how the significance and essence of this laboratory object evolved with its use as a clinical and research tool. Researchers had hoped that the test would sort the intersex into just two categories, male and female. Instead, the sex chromatin helped to multiply categories of the intersex, distinguished them from inverts, underpinned psychosocial gender as a new dimension of sex difference, and in the process had its own identity refashioned. Today, we call it the Barr body and its story reminds us of the power and limit of biotechnologies to determine who we are.

The easiest way to distinguish male from female was to count the smallest chromosomes. If there were four, then they assumed that the sample came from a female; if five, then a male. After verifying this assumption with the recorded sex of the samples, they examined cells in a bone marrow sample taken from a Klinefelter’s syndrome patient. They concluded that these were of the ‘‘female type’’ and that ‘‘there is agreement between the diagnoses of genetic sex by the presence of ‘sex chromatin’ and by direct examination of the chromosomes.

NATHAN Q. HA

This article is about the hopes and the uncertainties that people expressed for what the sex chromatin test could do and what it could tell them. It is also about the making of a new technology for diagnosing ‘‘true sex’’ from bodily tissues that were not obviously sexual, like skin or cheek swabs. Initially a serendipitous discovery, the sex chromatin was fashioned into an authoritative, medical tool that could purportedly separate male from female, homosexual from heterosexual, and normal from abnormal. In what follows, I will make three major arguments. First, I will demonstrate how the sex chromatin satisfied social expectations that only two sexes existed. Even if the exact relationship between the sex chromosomes and chromatin remained ambiguous, the presence or absence of the chromatin provided a binary answer to a question presumed to have only two possibilities. Thus, the sex chromatin re-presented the essence of genetic sex. Second, I will argue that the chromatin test helped to erase old sexual identities and create new ones. After the test, inverts became homosexuals and transsexuals, psychological gender emerged as a dimension of difference distinct from biological sex, and two new kinds of intersexuals were minted. Third, in the most ironic twist of all, I will show how these new classes of intersexuals provided evidence that would re-identify the sex chromatin itself. The result was a resolution of a long-standing uncertainty regarding the relationship between the sex chromatin and X chromosomes. Together, these recursive histories of the sex chromatin test demonstrate how social expectations help to constitute an emerging medico-scientific technology, and how that technology can in turn reformulate the cultural expectations that gave it meaning.

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Fertility Rates Among Non-Mosaic XXY; At Odds With Real Life Experience

Klinefelter syndrome (KS) is the one of the most frequent chromosomal disorder affecting 1/500–600 male newborns in the general population. The vast majority of the cases shows the 47,XXY karyotype, although mosaicism (46,XY/47,XXY) or higher-grade X aneuploidies can be rarely detected. Despite its high incidence, KS frequently remains undiagnosed and it is suspected later in adulthood after a diagnostic workup for hypogonadism, couple’s infertility, and/or sexual dysfunction.

Approximately 90% of adult men with homogeneous KS suffer from non-obstructive azoospermia (NOA), while fertility in mosaic KS seems to be less severely affected. Fathering is an important aspect for Klinefelter patients. Maiburg et al. performed a survey on 260 adults with KS and showed that most couples would like to have children and show a positive attitude toward assisted-reproductive techniques (ART). Infertility has been considered an untreatable disease in Klinefelter patients for many years. However, testicular sperm extraction (TESE), associated with ART, were found to be a valuable option for azoospermic men with KS to father a child, due to the presence of residual foci with preserved spermatogenesis

A recent systematic review and meta-analysis evaluated the outcomes of sperm retrieval by conventional TESE (cTESE) and by micro-surgical TESE (mTESE)in 1248 individuals with KS (Corona et al., 2017). Authors reported an average sperm retrieval rate (SRR) of 44% (43% and 45% after cTESE and mTESE, respectively), which is similar to that reported for men without KS. However, these meta-analytic data do not necessarily reflect the rates of SR that physician observe in clinical practice, which is typically lower than 50%. Moreover, results of meta-analysis should be interpreted according to the limitation of the study itself (inclusion of small, single centre studies, effect of un-adjusted confounders).

These meta-analytic data do not necessarily reflect the rates of SR that physician observe in clinical practice, which is typically lower than 50%. Moreover, results of meta-analysis should be interpreted according to the limitation of the study itself (inclusion of small, single centre studies, effect of un-adjusted confounders).

These observations prompted us to conduct a multicenter collaborative study to investigate the rate of and potential predictors of sperm retrieval by TESE in a cohort of azoospermic patients with KS presenting for primary couple’s infertility in the real-life setting.

With the recent improvements of TESE and ICSI procedures infertility has been no longer considered an untreatable disease in Klinefelter patients. In this context, most studies investigating TESE outcomes in patients with KS depicted conflicting results, in spite of having been generally rated of limited quality. A recent review showed that SRR in Klinefelter patients was approximately 50% world wide, thus similar to that of men without genetic abnormalities. However, these results appear to be unrealistic and even far from what physicians typically observe in the clinical practice.

The aim of this cross-sectional, real-life study was to investigate the prevalence of and possible factors associated with a positive SR in a cohort of white-European azoospermic patients with KS undergoing TESE at seven academic Andrology centres.

  • Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
  • Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
  • Division of Urology; A.O.U. Città della Salute e della Scienza di Torino – Presidio Molinette; Turin, Italy
  • Andrology Unit, University Hospital S. Orsola, Bologna, Italy
  • Fundació Puigvert, Department of Andrology, Universitat Autonoma de Barcelona, Barcelona, Spain
  • Department of Urology and Andrology, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
  • Department of Urology, AO Papa Giovanni XXIII, Bergamo, Italy


Of clinical relevance, we found that only one out of five KS men had positive SR in the real-life setting. Moreover, we failed to find any clinical, hormonal or procedural factors associated with SRR. These findings confirmed previous studies, where in contrast meta analytic data reported a significant higher SRR.

So far, there is a lack of reliable clinical and biological predictors for sperm retrieval success in NOA patients with KS. Advanced paternal age has been considered a negative predictive factor for SR in Klinefelter men undergoing TESE. Ozer et al, showed that TESE had better outcome before the critical age of 30.5 years, while other Authors suggested that TESE should be performed before 35 years. Recent evidence, however, support the lack of association between age and SR outcome. It has been shown that performing TESE between 15 and 23 years did not increase the SR rate compared to adult KS patients (25–29 years). We also confirm that SRR was not influenced by patient’s age in a real-life study with a large cohort of Klinefelter men.

According to this view it has been postulated that the progressive hyalinization and fibrosis of seminiferous tubules that is accelerated with the onset of puberty in KS is not ubiquitous and it is possible to observe tubules with normal residual activity. The impaired spermatogenesis could also be caused by an intrinsic problem of the germ cells, possibly linked to (epi)- genetics of the X surplus chromosome.

Testicular volume has been considered a possible factor associated with TESE success in Klinefelter patients, for example, showed that testicular volume was significantly higher in men with positive SRR. However, there are several studies reporting that testicular atrophy does not affect the success of SR (Corona et al., 2017; Franik et al., 2016; Garolla et al., 2018; Majzoub et al., 2016; Ozer et al., 2018; Vicdan et al., 2016). Garolla et al. (Garolla et al., 2018), indeed, observed a 23% SRR even in KS patients with testicles <1 mL. Our results support these findings since we failed to find any relationship between testicular volume and SRR in NOA patients with KS.

The clinical strength of our study is several-fold. First, we showed a low rate of positive sperm retrieval (up to 21%) in azoospermic men with KS in the real-life setting, thus suggesting that the crude data coming from meta-analytic studies cannot be routinely used in the everyday clinical practice.

There are conflicting results showing the association between serum hormones levels and TESE outcome in Klinefelter patients. Higher serum testosterone levels were found in Klinefelter men with positive SR as compared to those with negative SR . Similarly, the combination of high testosterone levels and low levels of LH was considered as positive predictive marker for SR in in both adolescents and adults with KS. Conversely, recent meta analytic data showed that serum hormones levels did not influence SRR in Klinefelter patients. We also showed that testosterone, FSH and LH levels were not different according to TESE outcome in our cohort of Klinefelter patients; however, additional studies are needed to explore the predictive value of serum hormones levels in KS

Testosterone treatment in KS has been previously considered as a negative factor for sperm recovery. In our population TRT was not associated with worse SRR as compared to that of men who did not received any supplementation. Our findings are in line with previous studies that
did not show any impact of testosterone treatment on spermatogenesis in adolescents and adults Klinefelter men. Therefore, some authors did not recommend postponing androgen treatment in adolescent boys with KS for fear of impairing their TESE results .

Lastly, the superiority of mTESE as compared to cTESE in NOA men has been extensively investigated in the previous literature but with conflicting results. This is particularly true also in the Klinefelter population. Only few reports have shown that mTESE could be associated with better SRR than cTESE. Conversely, our results, in agreement with recent studies showed that TESE technique is not associated with SRR.

Further strength of present study is that we have comprehensively investigated a large homogenous group of patients with a detailed hormonal evaluation, and an accurate assessment of possible confounders for impaired semen parameters, such as recreational habits and health comorbidities. However, none of these parameters were found to be associated with SRR.

The clinical strength of our study is several-fold. First, we showed a low rate of positive sperm retrieval (up to 21%) in azoospermic men with KS in the real-life setting, thus suggesting that the crude data coming from meta-analytic studies cannot be routinely used in the everyday clinical practice. Second, we cross-sectionally showed that clinical, hormonal and procedural factors are unable to predict the SRR in patients with KS. In this context, we believe that Klinefelter patients should be carefully counselled regarding their chance of retrieving spermatozoa after TESE. Further strength of present study is that we have comprehensively investigated a large homogenous group of patients with a detailed hormonal evaluation, and an accurate assessment of possible confounders for impaired semen parameters, such as recreational habits and health comorbidities. However, none of these parameters were found to be associated with Sperm Retrieval Rates.

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Cognitive and Neurological Aspects of Sex Chromosome Variations

Sex chromosome variations (SCV) are characterised by an atypical variation in the number or function of sex chromosomes. They are some of the most common genetic differences in human beings, and include 47 XXY; one in six hundred live births, 45X ; one in two thousand and 47 XYY; one in one thousand. However, by comparison with other chromosomal variations, such as Trisomy 21 (one in six hundred), clinicians have relatively little awareness about diagnosis or management of associated cognitive, psychiatric, and neurological symptoms.

These circumstances create a potential gap in clinical practice, with risk of missed diagnoses and high disease burden for patients who might otherwise receive treatments that would improve outcomes. As an example, about 50–85% of individuals who are XXY or XYY are not identified. Taken together with evidence that earlier detection could positively affect psychosocial, cognitive, physiological, and reproductive outcomes, it is imperative for health professionals to increase their familiarity with this group of SCV’s.

In addition to improvements in clinical practice, increased understanding of SCV’S provide an important opportunity to advance knowledge of sex-related differences in clinical disease in general. Advances in genomics and neuro-imaging research have made it increasingly possible that genotype–phenotype links will be established in the foreseeable future. Sex chromosome variations are ideal models for investigation of genotype–phenotype correlations because of their well defined genetic basis and relatively well described phenotypic characteristics.

Cognitive and Neurological Aspects of Sex Chromosome
Aneuploidies:
David S Hong, Allan L Reiss

Targeted research can elucidate how disrupted expression of sex chromosome genes and aberrant sex hormone production specifically affects cognitive and neurological function, and how this disruption can affect sex differences in clinical patho-physiology in general. Many immunological, cognitive, and motor features associated with sex chromosome differences are also commonly associated with disease states that have highly skewed sex differences in prevalence and symptom-atology. As such, improved knowledge of the inter-relation between genetics and nervous system function in sex chromosome differences can provide clinicians with an expanded understanding of mechanisms underlying sex differences in the nervous system.

In this Review, we summarise the major clinical features of sex chromosome variations, focusing mainly on XO (Turner’s), XXY (Klinefelter’s), and XYY (Jacobs), although we also briefly review other supernumerary sex chromosome variations. We present cognitive, motor, and other neurological outcomes associated with these variations, and mechanistic models and treatment frameworks that are used. Additionally, we delineate clinical features for each of these variations and discuss how continuing research in this area has broad implications for future understanding of sex differences in cognitive and neurological functioning in human beings.

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The Genetic Origins of Sex Differences in Disease

It took almost 15 years for scientists to sequence and publish a complete accounting of the human genetic code — the 3 billion base pairs along the double strands of DNA that serve as a blueprint for the body’s functions and pass traits from parents to offspring.

Now, approximately 15 years after the human genome was first sequenced, current discoveries represent just the beginning when it comes to the genetic origins of disease and the ever-expanding number of individual human genome sequences available to study. Researchers currently utilize what are called genome-wide association studies (GWAS) to discover hundreds of associations between genetic variations and specific diseases and disorders shared among individuals. But to date, very few researchers have fully explored how correlations between genes and disease may be different in women and men.

Few researchers have explored how genes, diseases, and biological sex interact.

Dr. Hongyu Zhao, an internationally known expert in the field of statistical genetics, has collected preliminary data to suggest that genetic pathways may relate to some diseases differently in women and men.

“Many human traits and diseases have sex or gender differences, and many diseases have a significant genetic component,” said Zhao, Department Chair and Ira V. Hiscock Professor of Biostatistics at Yale School of Medicine. “However, most analyses of genetic data assume the same effect for both women and men or use a methodology that is not calibrated to detect potential sex differences.”

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