Tag: uterus

Most detailed map of uterine lining yields clues about endometriosis

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An atlas of endometrial cells helps reveal its complexity

Connect Images / Alamy

We now have the most detailed map ever made of the endometrium, or the inner lining of the uterus. This will significantly improve our understanding of reproductive health and common conditions such as endometriosis.

The endometrium is one of the most dynamic organs in the body. Each menstrual cycle, it thickens in preparation for pregnancy and, if a pregnancy doesn’t occur, sheds its top layer during menstruation.

Despite the endometrium’s…

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September 3, 2024
Understanding the mechanisms behind embryonic diapause in hungry mouse mums

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It’s challenging to sustain a pregnancy when food is short, or conditions are otherwise tough. That’s why many mammalian embryos can postpone their growth to get through periods of environmental stress and then re-enter development when conditions improve. This stalling of development is known as embryonic diapause, and understanding the mechanisms behind it might help improve infertility treatments, such as embryo freezing. Now, researchers at the Center for Excellence in Brain Science and Intelligence Technology, the Chinese Academy of Sciences in Shanghai, China, have discovered how nutrient depletion is sensed by embryos growing in hungry mouse mums to induce diapause. They publish their study in the journal Development on 11 April 2024.

Lack of food is a known trigger of embryonic diapause, but it has not been clear how nutrient depletion in the mother’s diet is sensed by the embryo. “Seasonal starvation is one of the universal environmental stresses in nature,” explained Professor Qiang Sun, who led the study. “However, the regulatory process of diapause in early-stage embryos is not fully understood. So, we decided to examine whether nutrient deprivation induces embryonic diapause.”

By comparing hungry and well-fed pregnant mice, the team discovered that embryos in the hungry mice did not implant into the uterus and their growth paused at an early timepoint, when the embryo comprises a hollow ball of cells called the blastocyst. These embryos remained viable and could start developing again when transplanted into a well-fed mother.

To work out which nutrients were important to induce diapause, the researchers grew early-stage mouse embryos in dishes that contained different nutrients. They found that embryos grown in dishes lacking protein or carbohydrates paused their development, whereas the embryos exposed to normal nutrient levels did not stall and kept on developing. The scientists then went on to reveal that nutrient sensors in the embryo can detect drops in protein or carbohydrate levels, which triggers the entry into diapause.

The finding that embryos grown without protein or carbohydrates can pause their development means that they can survive longer in the lab. In the future, this finding might lead to improvements in fertility treatments, which currently include approaches such as embryo freezing. “We think our study can inspire the development of new methods for human embryo preservation,” said Professor Sun. “Embryo cryopreservation is a widely used approach, but there is still no consensus on when cryopreserved embryos can be thawed and transferred into the uterus. Many clinical studies have shown that traditional frozen embryo transfer can increase the risk of problems during pregnancy. Therefore, it is necessary to develop alternative methods to preserve embryos.”

Studies focusing on diapause may even have long-term implications for cancer treatments.

Dormant cancer cells which persist after chemotherapy resemble the diapaused embryos. Consequently, we hypothesize that delving into the mechanism of diapause may have positive implications for cancer treatment and decreasing the chances of relapse.”

Professor Qiang Sun

Source:

The Company of Biologists

Journal reference:

Ye, J., et al. (2024). Nutrient deprivation induces mouse embryonic diapause mediated by Gator1 and Tsc2. Development. doi.org/10.1242/dev.202091.

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April 12, 2024

California universities are required to offer abortion pills. Many just don’t mention it.

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The college senior at California State University-San Bernardino worked 60 hours a week at two jobs. She used birth control. Motherhood was not in the plan. Not yet. “I grew up poor. And I don’t want that for my children, like, ever,” she said.

She wanted a medication abortion. It’s a two-step process: one drug taken at a doctor’s office, and another a day later to induce cramping and bleeding and empty the uterus. Gomez didn’t bother going to the university health clinic, thinking it was only for basic health needs.

She ended up driving more than 300 miles and paying hundreds of dollars in medical and travel expenses to obtain a medication abortion. She missed a month of classes, which put her graduation date in jeopardy. She had no idea she was entitled to a free medication abortion right on campus.

An LAist investigation has found that one year after California became the first state to require its public universities to provide abortion pills to students, basic information on where or how students can obtain the medication is lacking and, often, nonexistent.

“I was really upset when I found out,” Gomez told LAist. “I had to really push myself to make that money happen.”

LAist initially found that 11 of 23 CSU campus clinics did not have any information about medication abortion on their clinic websites, nor did they list it as a service offered. Of the University of California’s 10 campuses, eight mentioned medication abortion on their clinic websites. (Five CSU campuses and one UC campus added information after LAist published a version of this article.)

Through conversations with students and faculty at multiple campuses, LAist found there was little information for students to obtain the pills.

“If I had known that, I would have taken advantage of it,” Gomez said. “I spent a lot of time driving around after work, switching schedules, putting my homework on the back burner.”

California legislators in 2019 passed the law that requires all the state’s 33 public university campuses to provide abortion pills. It took effect in January 2023.

“We wanted to make sure that students, female students, had access to this right,” said Connie Leyva, the former Pomona-area state senator who authored the bill.

The legislature created a $10.3 million fund of privately raised money to help universities implement the new law. Each campus received $200,000 in one-time funding to pay for the medication and cover costs such as facility upgrades, equipment, training, telehealth services, and security upgrades.

The funding did not include any requirement that campus clinics inform students the medication was available to them.

Leyva said she doesn’t recall any conversations about “including something on advertising that you could get a medicated abortion on campus.” She said she’s disappointed in the law’s implementation, but not surprised.

“Everything starts at the top. And if the president or chancellor of the university knows they have to offer it, but if they don’t agree that women should have access to abortion services, then they might just think, ‘We’ll leave it off, we don’t have to worry about it,’” Leyva said.

Spokesperson Ryan King said UC President Michael Drake was not available to comment.

“The student communities at each UC campus are unique,” Heather Harper, a spokesperson for UC Health in Drake’s office, wrote in an email. “As a result, communication to students at each location takes different forms and may include website content, flyers, emails, person-to-person conversations or other methods.”

The office of CSU Chancellor Mildred García did not reply to a request for comment.

At Gomez’s San Bernardino campus, abortion as an option was mentioned only in one place: in small letters on a poster inside exam rooms at the health center.

A student wouldn’t see that until they were already waiting for a doctor or nurse.

“We need to work harder if there is a student who needed the service and wasn’t aware that they could access it through us and not have to pay for it,” said Beth Jaworski, executive director of health, counseling, and wellness at CSU-San Bernardino. “But it’s one student. We haven’t been providing the service very long. It’s been just about a year now.”

Medication abortion has since been added to the list of services on the clinic’s website.

Ray Murillo, California State University’s interim assistant vice chancellor of student affairs, said he and other administrative staffers are developing guidance so campuses share the same information “to help in our training efforts for the frontline staff and providers when they’re being asked questions about the service and what we provide.”

Gomez wants more done, including flyers, emails, and social media posts directed at both faculty and students.

“You want to market the football games, you want to market the volleyball games. Why is that important, and abortions are not?” she said.

Gomez did graduate in December 2023, becoming the first person in her family to earn a bachelor’s degree. But she’s angry at her alma mater for keeping the abortion pills a secret.

This article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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April 2, 2024

99mTc-maraciclatide holds potential as a non-invasive test for early-stage endometriosis
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The presentation summarized the preliminary findings from patients with known or suspected endometriosis who were imaged with a SPECT-CT camera and subsequently underwent planned laparoscopic surgery, a key-hole surgical procedure to establish the presence, absence and location of endometriotic lesions. The imaging findings were compared to the surgical and histology reports and indicate that ^99mTc-maraciclatide holds potential as a non-invasive test for early-stage endometriosis.

Specifically these preliminary findings demonstrate that ^99mTc-maraciclatide has the potential to:
- Visualize superficial peritoneal endometriosis which is found in the thin peritoneum lining which covers the abdomen and pelvis, and currently can only be identified accurately by surgery. This subtype accounts for c. 80% of all endometriosis diagnoses. In the patients in this study ^99mTc-maraciclatide correctly identified superficial peritoneal endometriosis in those who went on to have this early-stage endometriosis confirmed by laparoscopy.
- Highlight areas of activity in patients with deep endometriosis (often found on the organs e.g., bladder, bowel, rectum, ovaries) and endometrioma (cysts which are commonly found in the ovaries)
The presentation also outlined a case study on one patient with superficial peritoneal endometriosis which had not been identified by ultrasound, but which had been visualized with ^99mTc-maraciclatide, and later confirmed by laparoscopic surgery.

The ongoing study which will recruit 20-25 patients in total is being led by Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford, together with Professor Krina Zondervan, Head of Department at the Nuffield Department of Women’s and Reproductive Health, University of Oxford. It is anticipated that the study will complete later this year.

^99mTc-maraciclatide is a radio-labeled tracer which binds with high affinity to the cell adhesion protein α_vβ₃ integrin and images angiogenesis (new blood vessel formation) which is known to be critical to the establishment and growth of endometriotic lesions.

David Hail, Chief Executive Officer of Serac Healthcare, said:

“These promising initial findings indicate that there is real potential for maraciclatide as a novel non-invasive method of diagnosing early-stage endometriosis. The ability to visualize the early-stage of this disease is particularly significant as it cannot be seen by other imaging modalities, which contributes to the almost nine year average delay to secure a diagnosis. We are hugely encouraged by these results and look forward to continuing this work with the world-leading specialists from Oxford University.”

Endometriosis is a common disease affecting many millions of women worldwide with pain and infertility. The current delay in diagnosis results in prolonged suffering and uncertainty. Therefore, a novel imaging tool to assist healthcare professionals in identifying or ruling out the disease is urgently needed.”

Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford

Professor Krina Zondervan, Head of Department at the Nuffield Department of Women’s and Reproductive Health, University of Oxford added:

“Superficial peritoneal endometriosis is the most prevalent form of the disease. It often affects younger women for whom earlier diagnosis could enable intervention at an earlier stage, with the potential to significantly change outcomes and improve prospects. At the Endometriosis CaRe Centre at the University of Oxford our studies focus on identifying novel genetic, diagnostic and therapeutic targets for endometriosis. We are delighted about the early results of the DETECT study and are looking forward to recruiting more patients to consolidate the data.”
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March 15, 2024
The effects of high maternal folate intake on the health outcomes of offspring

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In a recent review article published in Nutrients, researchers summarized what is known about the effects of excessive folic acid (FA) supplementation for mothers on children.

Study: Risk of Excess Maternal Folic Acid Supplementation in Offspring. Image Credit: luchschenF/Shutterstock.com

They conclude that while folate is a crucial nutrient, higher than necessary maternal FA intake may have adverse effects on their offspring.

Folate is an essential nutrient

Water-soluble vitamin B9, or folate, is needed for red blood cell (RBC) formation and to promote healthy cell growth and functioning. Doctors consider it necessary during pregnancy and lactation for fetal and placental growth, for the enlargement of the uterus, to reduce the risk of the child developing congenital disabilities in the brain and spine, and otherwise improve cardiovascular and reproductive health.

Folate can be found naturally in some foods, such as beans, peas, green leafy vegetables, and nuts. However, synthesized FA has been distributed widely in fortified food and nutrient supplements. Once consumed, it facilitates methyl group transfer among molecules, facilitating nucleotide synthesis and the metabolism of amino acids. Specifically, it is involved in methyl-donor metabolism.

Adequate FA supplementation has been associated with higher birth and placental weight and a lower risk of children being small for their gestational age and low birth weight. It also reduces the likelihood of neural tube defects (NTDs).

Continuing supplementation into the second and third trimesters has been shown to have sustained benefits for the neurocognitive development of children up to 11 years old. These included emotional intelligence, word reasoning, semantic processing, verbal-executive and motor function, attention, communication, and social competence.

Maternal deficiency of folate has been linked to numerous adverse outcomes, including elevated blood pressure and overweight in children. However, the availability of fortified foods and supplements has significantly raised folate levels in serum, RBCs, and overall, and recent studies have raised the possibility of adverse consequences of excess supplementation.

FA supplementation and ASD

Maternal intake of folate has been associated with autism spectrum disorder (ASD) incidence in addition to its neurodevelopmental benefits. A study in Norway found that FA intake starting four weeks before the pregnancy began and continuing for 12 weeks was protective against ASD.

However, a more recent study in the United States found a ‘U-shaped’ relationship between ASD risk and the frequency of maternal multivitamin supplementation. This suggests that ASD risk is highest at very low and very high levels of supplementation.

Another analysis indicates that unmetabolized folic acid (UMFA) levels in the cord blood could be positively associated with ASD risk, particularly in Black children, but further research is needed to shed light on these mechanisms.

Insights from mouse models

While well-designed mouse models can provide important information on the effects of high FA supplementation that cannot be ethically researched using human experiments, the timing and duration of supplementation, concentration of FA, how FA was administered, and the possibility of differential effects depending on the sex of the offspring must be considered.

Researchers used microarrays, Western blotting, ribonucleic acid sequencing (RNA-seq), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to analyze the effects of FA.

Results from some studies indicate that mice exposed to an intermediate level of FA had more gene changes. In terms of sex-based differences, some genes were more affected in female mice while others were more affected in male mice, leading to differential effects in the placenta, embryonic brain, and early postnatal brain. There were also indications that FA could affect brain development early in life but lead to lasting changes in behavior into adulthood.

While maternal FA deficiency has been implicated in NTD, excess supplementation has been associated with reduced placental and embryonic weights, smaller hippocampal areas, and increased weight gain in male but not female offspring. Observed neurodevelopmental impacts included short-term memory impairment, hyperactivity-like and repetitive behavior, and increased anxiety in mouse pups.

Findings varied across studies, but there is clear evidence that excess maternal FA intake can have long-term influences on physical and behavioral outcomes. It may also be implicated in glucose metabolism and reproductive disorders, but there are no indications that there are transgenerational inheritance effects.

Conclusions

Concerns about maternal folate deficiency, but FA supplements and fortified foods are now widely available, and excess intake may have widespread effects on the central nervous system.

While there is now growing evidence of detrimental effects in addition to benefits, there is a need to translate learnings from mouse models to studies on humans and explore the sex-linked impacts. Additionally, focus should be given to new forms of FA supplementation that can mitigate the potential harms of currently available supplements.

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March 8, 2024

A government video would explain when abortion is legal in South Dakota

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South Dakota lawmakers want state officials to create an educational video to help doctors understand when they can end a pregnancy without risking prison time under the state’s near-total abortion ban.

It’s an example of how states are responding to the national controversy over what exceptions to abortion bans actually mean. Critics point to reports of women developing dangerous complications after hospitals in states with strict abortion laws refused to terminate their pregnancies.

South Dakota legislators are moving a bill that would direct the state Department of Health to work with the attorney general and health and legal experts to create educational material, including a video, and publish it on its website.

The legislation is the first of its kind in the country, according to Susan B. Anthony Pro-Life America, an anti-abortion group.

The bill says the video would explain how South Dakota law defines abortion. Republican Rep. Taylor Rehfeldt, who introduced the bill, said treatments for miscarriages or an ectopic pregnancy —when a fertilized egg implants outside the uterus — do not count as abortions, and therefore are allowed.

The video would also discuss conditions that can threaten the life or health of a pregnant woman, and the criteria that providers might use to decide the best course of treatment. Rehfeldt said she expects the video to address when these medical conditions may need to be treated with an abortion, including how sick a patient needs to become.

Rehfeldt, a nurse anesthetist with a personal history of high-risk pregnancies, said she introduced the bill after hearing from health care providers who want guidance about the state’s abortion law.

“They said that they were confused and not sure when they can intervene,” Rehfeldt said. “I think it’s important that we provide that clarification because we all want moms to be taken care of.”

South Dakota has one of the nation’s strictest laws, prohibiting abortions unless they’re needed to save the life of a woman. There are no exceptions for preventing serious injury to the mother or in cases of fatal fetal anomalies, rape, or incest. Providing an illegal abortion is a felony that can be punished with two years in prison.

The state also has high rates of infant and maternal mortality, especially among Native Americans. Some South Dakota women have already been harmed because of the law after they were denied or received delayed abortions, according to Amy Kelley, an obstetrician and gynecologist in Sioux Falls.

Rehfeldt is confident her bill will pass the Republican-controlled legislature because the proposal has support from the governor’s office, health department, one of the state’s largest hospital systems, and state and national anti-abortion groups.

Anti-abortion advocates support the bill even though some groups, such as the Charlotte Lozier Institute, say exceptions to abortion bans are already clear. The group says state laws use language such as “reasonable medical judgment,” terms that hospitals should understand since such standards are often used in malpractice cases.

“Abortion activists have spread the dangerous lie that pregnant women in states with pro-life laws cannot receive emergency care,” Kelsey Pritchard, a South Dakota-based official with Susan B. Anthony Pro-Life America — which is affiliated with the Lozier Institute — said in a news release. “This patently false allegation that is used to justify the abortion industry’s agenda for no limits on abortion is putting women’s lives in danger.”

But abortion rights advocates say many doctors are afraid to provide critical care because of vaguely worded exceptions to abortion bans. Many say the only way to protect providers and their patients’ health is to repeal bans.

Nisha Verma is an OB-GYN in Georgia, where abortion is generally banned once fetal cardiac activity can be detected, typically around six weeks. Verma, who has provided abortions, is also a spokesperson for the American College of Obstetricians and Gynecologists.

“I understand the desire to grasp for anything that helps us provide care for our patients,” Verma said. But “there’s no way that you can create a video that talks about any type of inclusive list of conditions where you can and can’t provide care.”

Several other states have tried to clarify exceptions to their bans, but the South Dakota bill is the most comprehensive, Pritchard said.

In Oklahoma, the attorney general’s office sent a memo on the subject to prosecutors and police. It said doctors should have “substantial leeway” to provide lifesaving abortions, and don’t need to wait until a patient is “septic, bleeding profusely, or otherwise close to death.” The memo also says doctors should be prosecuted only if there’s evidence of criminal intent or a pattern of similar behavior.

Kentucky’s attorney general wrote an advisory opinion on the topic; Louisiana’s health department published a rule listing “medically futile” fetal conditions that can legally justify an abortion. Texas lawmakers added protections for doctors who end ectopic pregnancies or pregnancies of patients whose water breaks too early for the fetus to survive. The legislation does not use the word “abortion,” and lawmakers eschewed publicity as they were passing it.

Texas’ Supreme Court, lawmakers, and several pro- and anti-abortion rights advocates have all asked the state’s medical board for more guidance. The board must respond by mid-March as to whether it will do so, according to the health care publication Stat.

Abortion rights supporters are divided about the value of supplying guidance on exceptions to the abortion law.

“I wish we weren’t having this conversation,” said South Dakota Rep. Oren Lesmeister, a Democrat. “I wish we wouldn’t have had the trigger law” that banned most abortions.

But given that the law does exist, Lesmeister decided to co-sponsor and vote for the bill in hopes it will help doctors and their patients.

Critics of the legislation include the ACLU of South Dakota, the regional Planned Parenthood organization, and the Justice through Empowerment Network, a South Dakota abortion fund.

Verma and Kelley, the obstetricians, said laws, videos, and other guidance can’t capture the complexity of when an abortion may be necessary.

For example, conditions that aren’t fatal on their own can become deadly when combined with other complications, they said. Then there’s the question of when situations become life-threatening, which can happen quickly in obstetrics.

“There’s not a line in the sand where someone goes from being totally fine to acutely dying,” Verma said.

Verma and Kelley said doctors use their own expertise but also take their patients’ views into account when responding to life-threatening situations. That’s because one patient who learns they have a 25% risk of dying might decide against continuing their pregnancy, while another might view it as a risk worth taking, they said.

Some patients are willing to die if it means their baby will live, Kelley said, and “we honor their choice even if we don’t always think that that’s the right choice.”

Rehfeldt said she understands the concerns outlined by Verma and Kelley. But she said her bill would give doctors and hospital attorneys confidence to distinguish between legal and illegal procedures.

“If you have an interpretation that’s coming from collaboration with the attorney general, as well as the pertinent medical professionals, as well as the current governor’s office, I don’t see how you would be worried about being charged with a crime,” Rehfeldt said.

Kelley said it’s difficult to feel assured by any abortion-related guidance from South Dakota government officials when it feels as if they don’t trust doctors. For example, she said, lawmakers required abortion providers to share information with patients that can be opinionated and misleading.

“So, it’s really hard for them to then say, ‘Oh, but trust us, you won’t get in trouble with this law, we’ll go with your judgment,’” Kelley said.

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February 27, 2024

Premature babies could be treated with an artificial uterus in 2024

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The EXTEND system has kept more than 300 preterm lambs alive

Partridge, E., Davey, M., Hornick, M. et al. (2023)

The groundwork is being laid for the first human trial of an artificial uterus, which could get the go-ahead from the US Food and Drug Administration (FDA) some time in 2024.

Artificial uteruses are designed to mimic the environment of the womb as closely as possible and may help support babies who are born extremely prematurely, at around 23 or 24 weeks’ gestation.

“The idea is to bridge the rough patch when they’re really struggling and carry them through to a point when they can do…

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December 27, 2023

Tag: uterus

Folate is an essential nutrient

FA supplementation and ASD

Insights from mouse models

Conclusions