Welcome to The Visible Embryo

 

 

Home-- -History-- -Bibliography- -Pregnancy Timeline- --Prescription Drugs in Pregnancy- -- Pregnancy Calculator- --Female Reproductive System- -Contact
 

Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

WHO International Clinical Trials Registry Platform


The World Health Organization (WHO) has created a new Web site to help researchers, doctors and
patients obtain reliable information on high-quality clinical trials. Now you can go to one website and search all registers to identify clinical trial research underway around the world!



Home

History

Bibliography

Pregnancy Timeline

Prescription Drug Effects on Pregnancy

Pregnancy Calculator

Female Reproductive System

Contact The Visible Embryo

News Alerts Archive

Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.
Content protected under a Creative Commons License.

No dirivative works may be made or used for commercial purposes.

 

Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
Google Search artcles published since 2007
 
 

Home | Pregnancy Timeline | News Alerts |News Archive Feb 10, 2014

 

Oxytocin's natural actions are just like those of a diuretic, and are crucial
to controlling the pathogenesis of autism via suppressing chloride levels.
In many brain disorders (childhood epilepsy, cranial trauma, etc.),
studies reflect abnormally high chloride levels.

Image credit: wikimedia.org






WHO Child Growth Charts

 

 

 

Oxytocin controls chloride, affecting onset of autism

The scientific community agrees that autism has its origins in early fetal life —and/or immediately after birth.

A team led by Yehezkel Ben-Ari, Inserm Emeritus Research Director at the Mediterranean Institute of Neurobiology (INMED), has made a breakthrough in the understanding of the autism disorder.

In an article published in Science, the researchers demonstrate that chloride levels are elevated in the neurons of mice used in an animal model of autism and those levels remained abnormally high onward from birth. However, the administration of diuretics to mice before birth corrected the deficits in their pups.

These results support the success obtained with diuretic treatment given to autistic children by the same researchers and clinicians in 2012. They showed that oxytocin, the birth hormone, brings about a decrease in chloride level during birth, which controlled the expression of autistic syndrome in the children.

Neurons contain high levels of chloride throughout the entire embryonic phase. As a result, GABA, the main chemical messenger of the brain, excites neurons in this phase instead of inhibiting them, in order to facilitate construction of the brain. Subsequently, a natural reduction in chloride levels allows GABA to inhibit and regulate the activity of the adolescent and adult brain.

In many brain disorders (childhood epilepsy, cranial trauma, etc.), studies reflect abnormally high chloride levels. Having made these observations, Dr Lemonnier's team (Brest), and Yehezkel Ben-Ari's team at Inserm carried out a clinical trial in 2012, based on the hypothesis that high chloride levels exist in the neurons of patients with autism. However, the researchers showed that administration of a diuretic to children with autism (which reduces neuronal chloride levels) had beneficial effects.

The results of the 2012 trial supported this hypothesis, but because high neural chloride levels could not be demonstrated in children with autism, it was not possible to prove the mechanism or justify universal use of a diuretic treatment.

In the present study, the research used two animal models of autism, a genetic model of Fragile X syndrome, the genetic mutation most frequently associated with autism, and a second model generated by injecting pregnant mice with sodium valproate, a product known to create abnormalities in children including autistic spectrum disorder.

A higher level of chloride in the brain

For the first time, the researchers recorded the activity of neurons at the embryonic stage and immediately after birth in order to observe modifications in chloride levels. These observations showed that neural chloride levels are abnormally high in both autism models. GABA strongly excites neurons, and researchers recorded aberrant electrical activities in the brain, which persist into the adult animals.

The fall in chloride level, a particularly impressive phenomenon seen at birth in control animals, is absent in both of the animal models showing high chloride level before and after birth. These high levels are believed due to reduced activity of a chloride transporter which would normally transport chloride out of the neuron.


"Chloride levels during delivery are determinants of the occurrence of autism spectrum disorder."

Yehezkel Ben-Ari, Emeritus Research Director, Inserm.


Researchers administered a diuretic treatment to the mother (in both animal models) for 24 hours shortly before delivery to see if this would restore brain function in the offspring. Subsequently, a drop in chloride level was re-established in the neurons several weeks following a single  diuretic treatment during birth. According to the research team, before birth treatment restored brain activity to approximately normal levels, and corrected "autistic" behavior in the animals once they became adults.

"These results thus validate the working hypothesis that led us to the treatment we developed in 2012," states Ben-Ari, principal author of the study.

The role of oxytocin in reducing neural chloride had also observed in 2006. Researchers had seen oxytocin, which triggers labor, also has many beneficial actions on the brains of newborns — including protective effects during delivery and even analgesic properties.


Oxytocin acts as a diuretic, reducing intracellular chloride levels.


In the present study, the team tested the long-term effects of blocking oxytocin before birth by blocking it in pregnant mice. Researchers then watched as this intervention reproduced the entire autism-like syndrome within the pups. Both in electrical as well as behavioural aspects identical to the two animal models of autism. So, oxytocin's natural actions are just like those of a diuretic, and are crucial to controlling the pathogenesis of autism via suppressing chloride levels.

"This data validates our treatment strategy, and suggests that oxytocin, by acting on the chloride levels during delivery, controls the expression of autism spectrum disorder," states Yehezkel Ben-Ari.

Taken together, these observations suggest that early intervention is essential for possible prevention of the disorder.

This work raises the importance of analysing data on deliveries where a drop in chloride has occurred. Indeed, complicated deliveries with episodes of prolonged lack of oxygen, for example, or complications during pregnancy, such as viral infections, are often seen as risk factors.


"Although it is controversial that epidemiological data suggesting scheduled caesarean deliveries may have increased the incidence of autism, these studies should be followed up and extended in order to confirm or refute this relationship. To treat this type of disorder, it is necessary to understand how the brain develops and how genetic mutations and environmental insults modulate brain activity in utero."

Yehezkel Ben-Ari, Emeritus Research Director at Inserm


Abstract
We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naïve mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.

Authors
Roman Tyzio, Romain Nardou, Diana C. Ferrari, Timur Tsintsadze, Amene Shahrokhi, Sanaz Eftekhari, Ilgam Khalilov, Vera Tsintsadze, Corinne Brouchoud, Genevieve Chazal, Eric Lemonnier, Natalia Lozovaya, Nail Burnashev, Yehezkel Ben-Ari1