How Endometriosis Impacts Areas Beyond the Pelvis After Surgical Removal

Light micrograph of a cross-section of an ovary revealing cysts caused by endometriosis

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Recent extensive research into the biology of endometriosis has revealed novel mechanisms through which this chronic condition significantly impacts women’s health, paving the way for enhanced treatment options. This landmark study analyzed data from over 1 million women and identified specific genes linked to endometriosis among individuals of African descent, a group historically underrepresented in previous research.

According to Shefali Setia Verma from the University of Pennsylvania, “We identified approximately 300 genes that warrant further investigation in this field.”

Understanding Endometriosis: Endometriosis is a chronic and often debilitating condition characterized by the growth of tissue similar to the endometrium in locations outside the uterus, forming painful lesions. It affects approximately 10% of women of reproductive age, often leading to symptoms such as fatigue, severe pain, and fertility issues. Furthermore, endometriosis has been linked to cardiovascular diseases, although the underlying biological mechanisms remain inadequately understood.

To address this, Setia-Verma and her team employed a “multi-omics” approach, combining analyses of genes, proteins, microbiomes, and symptoms associated with endometriosis to create a comprehensive understanding of the condition. The researchers examined data from 14 global biobanks, compiling information from over 1 million women.

The team’s initial analysis uncovered 58 genomic regions related to endometriosis, with 27 of these being previously unidentified. Detailed scrutiny led to the identification of 314 genes associated with the disorder. Notably, this study highlighted three genetic regions linked to endometriosis detectable solely in individuals with African ancestry.

Among the most strongly associated genes, many were found to be involved in immune response, inflammation, and cellular motility. This is particularly significant as endometriosis involves cells growing inappropriately, suggesting the condition may relate to the biological processes governing cell migration rather than just misplaced tissue growth. “This insight may lead to the development of treatments targeting cell movement,” adds Setia Verma.

The association with inflammation and immune response may also clarify why endometriosis affects broader health issues, including cardiovascular disease, arthritis, and depression. Persistent inflammation going untreated can result in various long-term complications. In the UK, for example, the average time for a diagnosis is 9 years. Dr. Setia Verma stresses, “Untreated pain and inflammation can lead to a range of chronic symptoms.”

The insights from this study have crucial implications for treatment approaches. Current therapies for endometriosis predominantly target hormonal pathways since estrogen can stimulate lesion growth and associated inflammation. However, if inflammation is a principal factor in symptomatology and broader health concerns, addressing these inflammatory pathways may provide a more effective therapeutic strategy, according to Setia Verma.

The researchers discovered links between specific genes and proteins related to endometriosis, cardiovascular disease, and the regulation of blood cholesterol and fats. “This essentially indicates an increased cardiovascular disease risk for individuals with endometriosis,” remarks Setia Verma.

Another insightful finding was that individuals with endometriosis often exhibit reduced levels of Bifidobacteria, beneficial bacteria crucial for gut health and immune system support. “This sheds light on how endometriosis contributes to broader systemic health risks beyond reproductive issues,” states Setia Verma. This warrants further exploration into the role of Bifidobacteriaceae as a potential target for innovative therapies.

The strength of this study lies in its diverse participant demographic. Nilfel Ramioglu from Oxford University notes, “Most endometriosis research has focused on individuals of European descent, which limits the applicability of findings and exacerbates inequalities in women’s health research.” Ramioglu emphasizes that these efforts signify vital progress toward inclusive advancements in endometriosis research. However, additional research is essential for drawing definitive conclusions. As she asserts, “While this kind of study identifies biological pathways needing exploration, further validation is necessary to establish whether targeting these pathways leads to improved patient outcomes.”

Source: www.newscientist.com

New Study Uncovers How the Pelvis Evolved and Helped Our Ancestors Stand Upright

The pelvis is often described as the keystone for upright locomotion. Over millions of years, it has undergone significant transformations, enabling us to walk on two legs more effectively than any other part of our lower body. However, the specifics of this remarkable adaptation have been largely unknown. Recent research has uncovered two crucial genetic changes that reshaped the pelvis, permitting it to evolve into the upright structure that our ancestors utilized while traversing the Earth.

Ardipithecus ramidus Humanity resided in Africa over 4 million years ago. Illustrations by Arturo Asensio, via Quo.es

Anatomists have long recognized that the human pelvis is distinct among primates.

In our closest relatives, African apes (chimpanzees, bonobos, and gorillas) possess hipbones that are tall, narrow, and flat from front to back. When viewed from the side, they resemble thin blades.

The pelvic structure of an ape supports large muscles essential for climbing.

In contrast, human hip bones rotate sideways, forming a bowl shape. This flaring of the hip bones allows for muscle attachment critical for maintaining balance while shifting weight from one foot to the other during upright locomotion.

Nonetheless, the mechanisms behind this transformation have been elusive until now.

In a recent study, Professor Terrence Capelini from Harvard University and his team pinpointed vital genetic and developmental shifts that facilitated the evolution from the pelvis of tetraleaf monkeys to bipedalism.

“Our findings illustrate a complete mechanistic shift in human evolution,” stated Professor Capelini.

“There is no parallel to this among other primates.”

The researchers analyzed 128 samples of embryonic tissue from humans housed in museums in the US and Europe, along with nearly 20 other primate species.

These collections included specimens over 100 years old, preserved on glass slides or in bottles.

Using CT scans and histological analysis, they investigated pelvic anatomy during the early stages of development.

Their research revealed that the evolution of the human pelvis unfolded in two major phases.

Initially, the growth plate shifted 90 degrees, widening the human ilium instead of extending its height.

Following this adjustment, the timeline for embryonic bone formation was altered.

Typically, bones in the lower body develop when chondrocytes align along the long axis of the growing bone.

This cartilage becomes rigid through a process known as ossification.

At the early stages of development, similar to other primates, human growth plates formed from the head and continued to develop.

However, by day 53, the growth plate had notably shifted vertically from its initial orientation, resulting in a shorter and broader hip joint.

“When I examined my pelvis, it wasn’t initially on my radar,” Professor Capelini remarked.

“I anticipated a gradual modification to shorten and widen it, but histology indicated a complete 90-degree reversal.”

Group of Australopithecus afarensis. Image credit: Matheus Vieira.

A further significant alteration was the timeline of bone formation.

In most cases, bones develop along the primary ossification center located in the center of the bone shaft.

However, in humans, the ilium diverges from this norm, with ossification beginning at the posterior region in the sacrum and expanding radially.

This mineralization remains restricted to the peripheral layer, while internal ossification is postponed by 16 weeks, allowing bones to grow and maintain their shape during their geometric transitions.

To uncover the molecular mechanisms driving these changes, the team employed techniques like single-cell multiomics and spatial transcriptomics.

The researchers identified over 300 active genes, including three with notable roles: Sox9 and PTH1R (which control growth plate shifts) and runx2 (which governs ossification changes).

The significance of these genes is underscored by diseases arising from their dysfunction.

For example, mutations in Sox9 can lead to Campomelic dysplasia, a disorder characterized by an abnormally narrow hip joint lacking lateral flaring. Similarly, mutations in PTH1R result in narrow hip joints and various skeletal disorders.

The scientists propose that these adaptations began with the reorientation of the growth plate around the time our ancestors separated from African apes, estimated to have occurred between 5 and 8 million years ago.

They believe the pelvis has served as a focal point for evolutionary transformations over millions of years.

As brain size increased, the pelvis encountered selective pressures known as the obstetric dilemma—the trade-off between a narrow pelvis for efficient movement and a broader one for accommodating the birth of larger babies.

Researchers suspect that the delay in ossification likely occurred within the last two million years.

The oldest pelvic fossil, dated at 4.4 million years, belongs to Ardipithecus from Ethiopia—a species exhibiting a blend of upright walking and tree-climbing features, with pelvic characteristics akin to those of humans.

The renowned 3.2 million-year-old skeleton of Lucy (Australopithecus afarensis) showcases further adaptations for bipedalism, including the distinctively flaring hip blades.

“From that point onwards, all hominin fossils displayed pelvises that diverged significantly from those of earlier primates,” stated Professor Capelini.

“The implications of brain size and its subsequent changes should not be interpreted through growth models applicable to chimpanzees and unassociated primates.”

“Models should focus on the developments between humans and their own lineage.”

“Post-fetal growth occurred against the backdrop of novel methods for constructing the pelvis.”

This study is set to be published in the journal Nature.

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G. Senevilas et al. The evolution of hominin bipedal walking in two steps. Nature Published online on August 27th, 2025. doi:10.1038/s41586-025-09399-9

Source: www.sci.news

A Woman’s Pelvis is Shrinking: Implications for Childbirth

Medical advances have changed childbirth – potentially enough to affect human evolution

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Research involving over 8,000 participants across three nations indicates that women’s pelvises have become narrower over the last 150 years. While several factors contribute to this change, it offers fresh insights that could prompt researchers to reevaluate the so-called “obstetric dilemma,” which pertains to the evolutionary constraints surrounding pelvic size.

The exact drivers of this change and its implications for health remain unclear. Nonetheless, a continued reduction in pelvic size could heighten the likelihood of requiring cesarean sections.

Maciej Henneberg, from the University of Adelaide, Australia, and his team revisited an existing dataset featuring 1,247 Australian women born from 1900 to 1984. They discovered that pelvic width decreased by 0.42 mm annually. In Poland, the pelvic width of 3,486 women reduced by 0.47 mm each year from 1880 to 1970, while in a sample of 320 Mexican women, the decline was 0.42 mm annually from 1900 to 1970.

“I find this compelling, considering that these regions, despite differences in height, show similar evolutionary trends,” remarks Philip Mitter Ecker from the University of Vienna, Austria.

“The dataset is impressive,” adds Leah Betty from University College London.

Henneberg posits that these findings suggest modern medical practices diminish the effects of natural selection on human pelvises. Historically, a baby too large or a birth canal too narrow often resulted in fatal outcomes for both mother and child. However, the introduction of safe, effective cesarean sections has lessened this evolutionary pressure, potentially leading to further narrowing of the birth canal and pelvis.

Mitteroecker agrees that cesarean sections are influencing the evolutionary forces at play in human birth anatomy. He predicts this trend may result in even narrower pelvises, as highlighted in his 2016 analysis, stating it represents the latest chapter in a long-standing narrative.

“Midwifery has ancient roots, uniquely human,” he explains. For thousands of years, women have supported each other during childbirth. This cultural tradition has mitigated selection pressures on the pelvis and birth canal, demonstrating how our actions influence our biological evolution. “In a way, cesarean sections are an extreme manifestation of this,” Mitteroecker concludes.

However, Betty remains skeptical that cesarean sections are the primary cause of the recent changes in pelvic width. She highlights that humans have also experienced increased height during the same period, likely due to improved nutrition and healthcare rather than evolutionary gene alterations.

“Diet plays a significant role in determining pelvic structure,” Betty notes. When undernourished, developing bodies prioritize certain organs, particularly the brain, over others. With adequate nutrition now available, bodies may be reallocating resources, leading to variances in proportions. “Different body proportions are certainly a possibility,” she observes.

Understanding the factors behind these changes is crucial for comprehending the challenges of human childbirth. However, the nature of this dilemma is still debated. In a 2024 study, Mitter Ecker and colleagues suggested that pelvic floor mechanics could be a significant contributor to narrowing, potentially heightening pressure on the pelvic floor and elevating the risk of incontinence.

It’s also feasible that both factors are at play. An April study involving 31,000 participants associated wider pelvises with easier childbirth, yet identified slower walking speeds and increased risk of pelvic floor conditions.

The implications of this dilemma extend beyond childbirth. Betty notes that competitive sports during childhood may also influence pelvic size, emphasizing that various environmental factors, including temperature, can affect the pelvis. Other studies tie the evolving obstetric dilemma to rising obesity rates, which may result in larger babies. Ultimately, a combination of these factors likely explains the observed changes, prompting researchers to classify the issue as a “multifactorial pelvis” challenge.

A narrower pelvis poses health implications, complicating vaginal births and potentially increasing the need for cesarean deliveries. “Nobody knows how long it will take to reach a point where natural childbirth ceases to exist,” remarks Renata Henneberg, one of the researchers on this new study and Maciej Henneberg’s wife.

Conversely, a narrower pelvis may reduce the incidence of pelvic floor issues, which can be quite severe. Childbirth can have long-lasting, detrimental effects on women’s lives,” Betty cautions.

Predicting future trends is complex, given the multitude of interacting factors. While fewer children may lead to decreased injury risks, later childbirth may counteract this. “Many changes are occurring simultaneously,” she reflects.

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Source: www.newscientist.com