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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.

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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development


Gene links chromosome errors to early pregnancy loss

Researchers have identified a common gene variant strongly associated with chromosome gain and loss in early human embryos. These errors in cell division, almost always fatal to an embryo, add to early pregnancy loss and IVF failure.

The findings were presented at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore.

Healthy human body cells contain 23 pairs of chromosomes, for a total of 46. However, errors during the cell replication process can cause the chromosomes to distribute unevenly, a condition known as aneuploidy.

"Early in human development, this process is particularly error-prone, affecting as many as 75 percent of embryos and often causing pregnancy loss as soon as five days after fertilization - before the mother even knows she is pregnant," explained Rajiv McCoy PhD, a postdoctoral researcher at the University of Washington and first author on the study.

Previous research has found a correlation between the age of the mother (but not the father) and the likelihood of aneuploidy (an abnormal number of chromosomes in a cell). In fact, it is the mother's genes that govern cell replication during the first few days of embryonic development. "However," Dr. McCoy said, "this relationship did not fully account for the variation in aneuploidy we found within each maternal age group, so we guessed a genetic factor was also involved."

Using data collected by collaborators at Natera, Inc., Dr. McCoy and colleagues at Stanford University analyzed more than 46,000 embryos from about 2,400 IVF patients, and found that rs2305957, a common variant on chromosome 4 in the mother's genome, was strongly associated with risk of aneuploidy. Furthermore, aneuploid embryos were more likely to have originated from patients who had experienced IVF failure in the past than those who had not, suggesting that aneuploidy may have been what caused the treatment to fail.

"Surprisingly, about half of women had this genetic variant, and that rate is fairly consistent across populations," Dr. McCoy said. "If it's so damaging to reproduction, why does it appear so often? Why isn't it selected against?"

One hypothesis is that for ancient humans, a lower chance of successful pregnancy per sexual encounter encouraged long-term bonding between men and women, which in turn increased paternal investment in each child, improving the child's safety and health. Thus, children who were born despite their mothers' reduced fertility may have been more likely to survive to adulthood and have their own children, passing the variant on to future generations. It is also possible that the variant plays multiple roles; while it reduces fertility, it may be beneficial in another context.

A gene located near rs2305957 provides a clue about what might cause the aneuploidy. The researchers strongly suspect that PLK4, a neighboring gene known to govern the distribution of chromosomes as cells divide, is involved, but not yet confirmed.

"It would be great if we could positively identify the gene, the causal variant, and the molecular mechanism that the variant affects," Dr. McCoy said. To gather evidence, he and his colleagues are examining other genomic data sets involving PLK4 expression to understand the variant's role in development. They also plan to study the variant in the context of human history, to assess its origins and explain why it remains common.

Abstract Presentation: Dr. McCoy presented his research on Thursday, October 8, 2015, at the Baltimore Convention Center.

Reference: McCoy R et al. (2015 Oct 8). Abstract: "Complex mitotic-origin aneuploidy in human embryos: Genetic risk factors and fertility consequences." Presented at American Society of Human Genetics 2015 Annual Meeting. Baltimore, Md.

"Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos"

Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency.

Chromosome number varies in humans

Pregnancy loss is often associated with a loss of chromosome number, a condition known as aneuploidy. When examining aneuploid embryos during in vitro fertilization cycles, McCoy et al. found a large genomic region associated with defects in maternal chromosome number (see the Perspective by Vohr and Green). This region contains a gene, Polo-like Kinase 4 (PLK4), that is known to affect chromosome segregation and has variants that correlate with an increased rate of maternal aneuploidy. Surprisingly, such variants occur at relatively high levels in human populations and may be under positive selection.

Authors: Rajiv C. McCoy, Zachary Demko, Allison Ryan, Milena Banjevic, Matthew Hill, Styrmir Sigurjonsson, Matthew Rabinowitz, Hunter B. Fraser, Dmitri A. Petrov

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Oct 13, 2015   Fetal Timeline   Maternal Timeline   News   News Archive   

Mis-segregating chromosomes

Image Credit: Stefano Santaguida, Angelika Amon, MIT











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