̽��ֱ�� of Cambridge - menstruation

Miniature ‘womb lining’ grown in lab could reveal secrets of menstrual cycle and early pregnancy

cjb250 — Mon, 10 Apr 2017 15:30:19 +0000

̽��ֱ��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.

̽��ֱ��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.

̽��ֱ��organoids are capable of generating both secretory (red) and epithelial (cyan) cells of the uterus. Image: Centre for Trophoblast Research

“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.

̽��ֱ��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.

Reference
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

Scientists at the ̽��ֱ�� 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.

These organoids provide a major step forward in investigating the changes that occur during the menstrual cycle and events during early pregnancy

Margherita Turco

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Women’s faces get redder at ovulation, but human eyes can’t pick up on it

fpjl2 — Tue, 30 Jun 2015 18:01:38 +0000

Previous studies have shown that men find female faces more attractive when the women are ovulating, but the visual clues that allow this are unclear. Now, new research investigating whether it might be to do with subtle changes in skin colour has shown that women’s faces do increase in redness during ovulation, but the levels of change are just under the detectable range of the human eye.

Researchers say this may mean that facial redness in females was once an involuntary signal for optimal fertility, but has since been “dampened” by evolution as it is more beneficial for females to hide or control outward signs of peak fertility.

Involuntarily signalling ovulation can prevent longer-term investment from males. In primate species that advertise ovulation, males only express sexual interest in females when they appear to be fertile. In humans, ovulation is less conspicuous and sexual behaviour is not restricted to the period of peak fertility.

̽��ֱ��research, published today in the open-access journal PLOS ONE, is the most complete objective study of female faces during the ovulatory cycle, say researchers. Twenty-two women were photographed without make-up at the same time every working day for at least one month in the same environment and using a scientific camera modified to more accurately capture colour (usually used for studying camouflage in wildlife).

A computer programme was designed to select an identical patch of cheek from each photograph. ̽��ֱ��participants also self-tested for hormone changes at key times dictated by the research team’s “period maths”.

A surge in luteinising hormone told researchers that ovulation would occur in roughly the next 24 hours, so they knew which photographs were taken when the women were most fertile. ̽��ֱ��team converted the imagery into red/green/blue (RGB) values to measure colour levels and changes.

They found that redness varied significantly across the ovulatory cycle, peaking at ovulation and remaining high during the latter stages of the cycle after oestrogen levels have fallen. Skin redness then dips considerably once menstruation begins. ̽��ֱ��research suggests facial redness closely maps fluctuations in body temperature during the cycle.

However, when running the results through models of human visual perception, the average difference in redness was 0.6 units. A change of 2.2 units are needed to be detectable to the naked human eye.

“Women don’t advertise ovulation, but they do seem to leak information about it, as studies have shown they are seen as more attractive by men when ovulating,” said Dr Hannah Rowland, from the ̽��ֱ�� of Cambridge’s Zoology Department, who led the study with Dr Robert Burriss, a psychologist from Northumbria ̽��ֱ��.

“We had thought facial skin colour might be an outward signal for ovulation, as it is in other primates, but this study shows facial redness is not what men are picking up on - although it could be a small piece of a much larger puzzle,” she said.

Primates, including humans, are attracted to red, say the study’s authors. Women may subconsciously augment the naturally-occurring facial redness during ovulation through make-up such as blusher or red clothing, they say.

“As far back as the 1970s, scientists were speculating that involuntary signals of fertility such as skin colour changes might be replaced with voluntary signals, such as clothing and behaviour,” said Burriss. “Some species of primate advertise their fertility through changes in the colour of their faces. Even if humans once advertised ovulation in this way, it appears that we don’t anymore.”

It may be that, during ovulation, women have a greater propensity for blushing when around men they find attractive, say the researchers. “Other research has shown that when women are in the fertile phase of their cycle they are more flirtatious and their pupils dilate more readily, but only when they are thinking about or interacting with attractive men,” said Burriss. “We will need to do more research to find out if skin redness changes in the same way”.

Rowland and Burriss first conceived of the experiment seven years ago, but it wasn’t until Rowland arrived at Cambridge that they were able to do the research, thanks to the ̽��ֱ��’s collegiate system. “We were able to recruit undergraduates in a number of colleges and photograph the women just before they had dinner in the college hall every evening. ̽��ֱ��collegiate routines and networks were vital to collecting data with such regularity,” said Rowland.

Past research shows men find female faces more attractive at peak fertility. A new study shows an increased redness of women’s face skin at the most fertile point of ovulatory cycle, but just under the threshold for detectability, ruling out skin colouration as a driver of the attractiveness effect.

Women don’t advertise ovulation, but they do seem to leak information about it

Hannah Rowland

Greg Peverill-Conti

Faces

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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