Nav: Home

Womb lining grown in lab could reveal secrets of menstrual cycle and early pregnancy

April 10, 2017

Scientists at the University of Cambridge have succeeded in growing miniature functional models of the lining of the womb (uterus) in culture. These organoids, as they are known, could provide new insights into the early stages of pregnancy and conditions such as endometriosis, a painful condition that affects as many as two million women in the UK.

The mucosal lining inside the uterus is called the endometrium. Over the course of the menstrual cycle, its composition changes, becoming thicker and rich with blood vessels in preparation for pregnancy, but if the woman does not conceive, the uterus sheds this tissue, causing the woman's period.

A team from the Centre for Trophoblast Research, which this year celebrates its tenth anniversary, was able to grow the organoids in culture from cells derived from endometrial tissue and maintain the organoids in culture for several months, faithfully reproducing the genetic signature of the endometrium - in other words, the pattern of activity of genes in the lining of the uterus. They also demonstrated that the organoids respond to female sex hormones and early pregnancy signals, secreting what are collectively known as 'uterine milk' proteins that nourish the embryo during the first months of pregnancy.

The findings of the study, funded by the Medical Research Council, the Wellcome Trust and the Centre for Trophoblast Research, are published today in the journal Nature Cell Biology.

"These organoids provide a major step forward in investigating the changes that occur during the menstrual cycle and events during early pregnancy when the placenta is established," says Dr Margherita Turco, the study's first author. "These events are impossible to capture in a woman, so until now we have had to rely on animal studies."

"Events in early pregnancy lay the foundations for a successful birth, and our new technique should provide a window into this events," adds Professor Graham Burton, Director of the Centre for Trophoblast Research, and joint senior author with Ashley Moffett of the study. "There's increasing evidence that complications of pregnancy, such as restricted growth of the fetus, stillbirth and pre-eclampsia - which appear later in pregnancy - have their origins around the time of implantation, when the placenta begins to develop."

Research in animal species such as mice and sheep has shown that factors secreted by the endometrial glands are critical for enabling a developing fertilised egg (known as the 'conceptus') to implant into the wall of the uterus. There is also strong evidence that the conceptus sends signals to the endometrial glands that then stimulate the development of the placenta. In this way, the conceptus is able to stimulate its own development through a 'dialogue' with the mother; if it fails, the result is loss of the pregnancy or severe growth restriction of the fetus.

Professor Burton and colleagues believe that using the organoids will allow them to investigate in greater detail how the conceptus communicates with the glands, identifying the full repertoire of factors released in response and testing their effects on placental tissues. His team will be collaborating with the Bourn Hall Clinic - a fertility clinic near Cambridge - to investigate whether parts of this circuitry are impaired or deficient in women experiencing difficulty in conceiving, and if so to devise potential new treatments.

The technique also enables the researchers to grow organoids from endometrial cancer cells. As proof-of-principle, this will allow them to model and understand diseases of the endometrium, including cancer of the uterus and endometriosis.

Organoid cultures have proven to be powerful tools for investigating the behaviour of other organ systems. Members of the Centre for Trophoblast Research are confident that their new advance will provide a much-needed window on events during the earliest stages of pregnancy, when the conceptus and mother first physically interact.

Turco, MY et al. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nature Cell Biology; 10 April 2017; DOI: 10.1038/ncb3516

University of Cambridge

Related Pregnancy Articles:

Paracetamol during pregnancy can inhibit masculinity
Paracetamol during pregnancy can inhibit masculinity Paracetamol during pregnancy can inhibit the development of 'male behavior' in mice.
The cost of opioid use during pregnancy
A new study published today by the scientific journal Addiction reveals that the incidence of neonatal abstinence syndrome -- often caused by mothers using opioids during pregnancy -- is increasing in the United States, and carries an enormous burden in terms of hospital days and costs.
New study: Pre-pregnancy BMI directly linked to excess pregnancy weight gain
It's well known that excessive weight gain during pregnancy can have a lasting negative impact on the health of a mother and her baby.
Pregnancy-specific β1-glycoproteins
Development of new strategies and novel drug design to treat trophoblastic diseases and to provide pregnancy success are of crucial importance in maintenance the female reproductive health.
Should hypothyroidism in pregnancy be treated?
When a woman becomes pregnant, many changes occur in her body.
Pre-pregnancy progesterone helps women with recurrent pregnancy loss
Women who have had two or more unexplained miscarriages can benefit from natural progesterone treatment before pregnancy, a new a study from the University of Illinois at Chicago shows.
Male pipefish pregnancy, it's complicated
In the upside-down world of the pipefish, sexual selection appears to work in reverse, with flashy females battling for males who bear the pregnancy and carry their young to term in their brood pouch.
Pregnancy leads to changes in the mother's brain
A study directed by researchers from the UAB and IMIM are the first to reveal how pregnancy causes long-lasting alterations in brain structure, probably related to improving the mother's ability to protect and interact with the child.
MRIs during pregnancy and outcomes for infants, children
In an analysis that included more than 1.4 million births, exposure to magnetic resonance imaging (MRI) during the first trimester of pregnancy compared with nonexposure was not associated with increased risk of harm to the fetus or in early childhood, although gadolinium MRI at any time during pregnancy was associated with an increased risk of a broad set of rheumatological, inflammatory, or skin conditions and, possibly, for stillbirth or neonatal death, according to a study appearing in the Sept.
The benefits of exercise during pregnancy
Women who exercise during pregnancy are more likely to deliver vaginally than those who do not, and show no greater risk of preterm birth.

Related Pregnancy Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".