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Developmental Biology - Infertility
Infertility More Common Than Imagined?
Embryos with two nuclei have an increased chance for an abnormal number of chromosomes...
Struggling with infertility? You are not alone. Infertility affects one out of every six Canadian couples. Some resort to in vitro fertilization, but with mixed results.
In a study published in Nature Communications, researchers from the University of Montreal Hospital Research Centre (CRCHUM) unveiled a mechanism that likely contributes to the low level of pregnancy success in some fertility clinics. This new information could ultimately increase women's chances of having a baby.
Healthy cells usually have one nucleus, which contains all our DNA - our genetic information. Embryos that are created in vitro in fertility clinics enabling women to have a child, often have cells with two nuclei known as binucleation.
As of today, many fertility clinics still transfer these so-called "binucleated embryos" back to the patient's uterus.
"In our study, we saw in mouse embryos that binucleation has profound consequences. Basically, binucleation increases the chances of the embryo developing a condition called aneuploidy, which reduces embryo health and could contribute to pregnancy failures.
We hope our results will help fertility clinics to select the best embryos to be transferred back to the patients. This step is one of the keys to success when it comes to in vitro fertilization. Ultimately it could increase some couples' chances of giving birth." says Lia Paim, first author and PhD student in Greg FitzHarris' lab.
This study is at the basic research stage and was carried out in the laboratory on mice. "Basic science experiments such as Lia's allow us to understand how embryos develop, to help inform our clinical colleagues how to select the best embryos in the clinic," added Dr. Fitzharris, CRCHUM researcher and professor at the Université de Montréal.
Infertility may be more common than we think — as the number of people with fertility problems has doubled since the 1980s.
Abstract
Tetraploidisation is considered a common event in the evolution of chromosomal instability (CIN) in cancer cells. The current model for how tetraploidy drives CIN in mammalian cells is that: a doubling of the number of centrioles that accompany the genome doubling event, leads to multipolar spindle formation and chromosome segregation errors. By exploiting the unusual scenario of mouse blastomeres, which lack centrioles until the ~64-cell stage, we show that tetraploidy can drive CIN by an entirely distinct mechanism. Tetraploid blastomeres assemble bipolar spindles dictated by microtubule organising centres, and multipolar spindles are rare. Rather, kinetochore-microtubule turnover is altered, leading to microtubule attachment defects and anaphase chromosome segregation errors. The resulting blastomeres become chromosomally unstable and exhibit a dramatic increase in whole chromosome aneuploidies. Our results thus reveal an unexpected mechanism by which tetraploidy drives CIN, in which the acquisition of chromosomally-unstable microtubule dynamics contributes to chromosome segregation errors following tetraploidisation.
Authors
Lia Mara Gomes Paim and Greg FitzHarris.
Acknowledgments
The work was funded by grants from the Natural Sciences and Engineering Research Council of Canada, Fondation Jean-Louis Lévesque, Canadian Foundation for Innovation and the Canadian Institutes of Health Research. LMGP is supported by a Fonds de Recherche du Québec—Santé Doctoral Scholarship. We thank Gilles Hickson, Jean-Claude Labbé, and Aleksandar Mihajlovi? for comments on the manuscript, Gaudeline Rémillard-Labrosse and Aurélie Cleret-Buhot for excellent technical support.
Information and statistics on fertility: Public Health Agency of Canada website
About the CRCHUM
The University of Montreal Hospital Research Centre (CRCHUM) is one of North America's leading hospital research centres. It strives to improve adult health through a research continuum covering such disciplines as the fundamental sciences, clinical research and public health. Over 1,861 people work at the CRCHUM, including 542 scientists and 719 students and research assistants. chumontreal.qc.ca/crchum @CRCHUM
About Université de Montréal
Deeply rooted in Montreal and dedicated to its international mission, Université de Montréal is one of the top universities in the French-speaking world. Founded in 1878, Université de Montréal today has 16 faculties and schools, and together with its two affiliated schools, HEC Montréal and Polytechnique Montréal, constitutes the largest centre of higher education and research in Québec and one of the major centres in North America. It brings together 2,500 professors and researchers and has more than 60,000 students. umontreal.ca
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