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Marie-Odile Soyer-Gobillard (born April 9, 1939) is a French biologist, Doctor of Science, Honorary Emeritus Director of Research at the French National Centre for Scientific Research (CNRS) and President of an association dedicated to scientific research.

At the Arago Laboratory, her scientific work, recognized worldwide, focused on the cellular and molecular study of protists, in particular dinoflagellates. She formed and led a cell and molecular biology team, which supported her scientific activity. She has progressively introduced the most advanced techniques for the study of marine cell biology.

Over the past ten years, she has become known to the general public for her studies on psychiatric disorders in children exposed in utero to synthetic hormones, in particular diethylstilbestrol (DES), as well as on their multigenerational effect. This work is carried out in close collaboration with the association Hhorages-France of which she is the President.. .

Early life and education
Marie-Odile Soyer-Gobillard was born in Sézanne, in Champagne, in 1939, into a bourgeois family of small industrialists. She is the eldest of five children. Her secondary education was at the College of Sézanne where she obtained her first Baccalaureate. After graduating, she enrolled in a new final year class at the end of which she obtained a second Baccalaureate in experimental sciences. She then studied science at the Faculté des Sciences de Paris Sorbonne and obtained a doctorate in science at the Pierre and Marie Curie University (Paris-VI).

Career
In September 1961, at only 22, after obtaining a Graduate Degree (Diplôme d'études supérieures), she joined the CNRS at the Observatoire océanologique de Banyuls-sur-Mer (OOB), a world-renowned marine laboratory, known as the "Laboratoire Arago", where she spent her entire career.

In 1974, she founded the Cell and Molecular Biology Department, dedicated to the study of the mechanisms that control the functioning of certain marine organisms used as models by researchers on, among other things, the structure of chromosomes, the proteins of the mitotic apparatus and the course of the cell-cycle.

From 1980 to 1989, she was an elected member of the Board of Directors of the Arago Laboratory. From 1987 to 1991 she was appointed member of the National Committee of the CNRS (section 28, Biology of Organisms) of which she was vice-president. From 1975 until her retirement in 2000, she was in charge of a research group, of the Electron Microscopy Service as well as of the Cell and Molecular Biology Department until 1995.

Volunteer involvement in associations
Following the American work of Herbst et al. in 1971 on the presence of clear-cell adenocarcinoma of the vagina in women who had prenatal exposure to diethylstilbestrol (so-called DES Daughters), the drug was contraindicated in pregnancy in the US by the Food and Drug Administration , but it was still prescribed in France until at least 1977. In France, since 1974 with the work of Dr. Henry-Suchet, 1975 with that of Professor Barrat, and since 1983, with the publication of an article in the French newspaper Le Monde based on the work of Dr. Anne Cabau , it was already known that Distilbène® caused birth defects in DES Daughters. Unknown then, however, was that the consequences of DES exposure are not limited to DES Daughters, nor to the reproductive tract, and that other synthetic sex hormones may produce the same effects.

Following her meeting with René Alexandre, Marie-Odile Soyer-Gobillard, as well as the families previously gathered, put together their observations. René Alexandre then presented the results of his research at the General Meeting of an active patients' association, Réseau D.E.S. France, founded in October 1994 by members of the previous association INFO-DES, itself a successor to the association DANE 45 (D.E.S-France). At this meeting, Professor Tournaire, a gynecologist, and the President, Anne Levadou, did not give any credence neither to these observations nor to the work presented by René Alexandre. For them, and for the doctors present, there was no relationship between exposure to Distilbene® and psychiatric disorders. René Alexandre was very affected by this rejection. He died 6 months later following a stroke.

Marie-Odile Soyer-Gobillard and four other concerned parents decided to take up the torch by founding the association Hhorages-France in 2002. The aim of the association is "to establish the cause-effect relationship between the use of synthetic sex hormones during pregnancy and all the disorders generated, in the short and long term, in children exposed in utero" – and more recently in the grandchildren – with an emphasis on psychiatric disorders, associated or not with somatic disorders, and to provide advice and support to the families heavily affected. Hhorages also promotes legal action, with cases being handled by a criminal justice attorney.

Hhorages continued to bring families together and then, in order to establish a cohort of those concerned, developed a detailed questionnaire with researchers and physicians. The resulting database was the starting point for some of her future scientific work and discoveries.

First Vice-president of Hhorages-France and President of its Scientific Board from 2002 to 2010, Marie-Odile Soyer-Gobillard then became president and Head of Research in 2010 – positions she currently holds. Within the framework of the research, she collects testimonies from member families and puts her scientific skills at the service of this research and of this fight, which is part of the wider fight for the recognition of the toxicity ofendocrine disruptors chemicals (EDCs).

From 2002 to 2012, she was President of UNAFAM 66 (French National Union of friends and families of people with mental illness and/or disability), Research Correspondent and Regional Delegate for Languedoc-Roussillon.

Since 2007 she is an appointed member of the College of Reviewers of Clinical Projects of the French National Institute of Health and Medical Research (INSERM) and a member of the Editorial Committee.

Since 2019, she is a sponsor of the mutual-aid group "L'Escale" in Perpignan, which provides support to adults with mental fragility.

Within the Arago Laboratory
At the end of 1961, Marie-Odile Soyer-Gobillard, then a young doctoral student who had just joined the CNRS, went to the Arago Laboratory for a one-month internship to collect biological material from marine plankton as part of her doctoral thesis, directed by Pierre-Paul Grassé, a renowned biologist, evolutionist and protistologist. She stayed at the Arago Laboratory where she pursued her entire scientific career.

On her arrival, Dr. Jean Théodorides, a specialist of Gregarinea (Sporozoa), then at the Arago Laboratory, taught Marie-Odile Soyer-Gobillard the first rudiments concerning planktonic marine protists. Thus, the first scientific articles she published were devoted to the description of several new species of Gregarinea, gastrointestinal parasites of certain pelagic copepod s (crustaceans of the plankton).

Marie-Odile Soyer-Gobillard then decided to pursue, with new methods, the earlier work of the protistologist, pioneer of cell biology, Edouard Chatton on free-living and parasitic Dinoflagellates (also called Peridinia). Chatton's major contribution was undoubtedly his proposal, in 1925, to divide the cellular world into two major groups: prokaryotes (without nucleus) and eukaryotes (with nucleus). In his doctoral thesis of 1920, he described the special nuclear division of the peridinians, but the kinetics and components remain poorly understood.

She then began to use the methods of classical cytology and cytochemistry, focusing on the preservation of particularly delicate cellular and nuclear structures. As this preservation work required the use of electron microscopy, the observations were first made in Paris (France), before the Arago Laboratory was equipped with one.

The purchase of the first ultramicrotome, a high-precision device, allowed the launch of a rudimentary but efficient electron microscopy (EM) department.

The year 1967 was a turning point because an international course in marine molecular biology was given at the Arago Laboratory, under the responsibility of Prof. Marie Goncharoff, a specialist in cell regeneration, with the help of Prof. Daniel Mazia, an American cytologist and cell biologist, known for his research which led to the isolation of the cellular structures responsible for mitosis. Since the laboratory was previously poorly equipped, the participants learned to use new tools such as ultracentrifuges and scintillation counters.

In 1968, Marie-Odile Soyer-Gobillard started working on the structure of Dinoflagellate chromosomes with Yves Bouligand, a specialist in cholesteric (or liquid crystal) structures.

In 1969, she described in Noctiluca, a bioluminescent dinoflagellate, responsible for "red tides", its amazing nuclear membrane and its development during sporogenesis, the structure of its mouth, and its contractile tentacle ,

In 1970, she also described for the first time the first striated contractile myonemes of the animal kingdom. They were later studied by Christine Métivier in her PhD thesis on the motility of Noctiluca, its structural organization, its ionic regulation and the characterization of its cytoskeleton.

In April 1970, Marie-Odile Soyer-Gobillard defended her thesis in Paris, one day away from her husband Jacques Soyer (1938-2019), then deputy director of the Arago Laboratory. She obtained her PhD in Science with the most prestigious mention "Very honorable with congratulations from the jury". In 1971, Professor Pierre Drach, director of the Arago Laboratory, and André Lwoff, researcher in biology and Nobel Prize winner in physiology or medicine, arrived in her laboratory. The quality of Marie-Odile Soyer-Gobillard's work was then noticed by André Lwoff, also a disciple of Chatton. After reading her thesis, he asked Marie-Odile Soyer-Gobillard to complete an unfinished manuscript by Chatton. To Chatton's observations and drawings on the cycle of Paradinium (a plasmodial protist), she added her own observations and the description of two new species. Thus, in 1973, she co-signed with him a posthumous article with a preface by André Lwoff.

In 1973, Olli Haapala, a Finnish cytogeneticist who had noticed Marie-Odile Soyer-Gobillard's previously published papers, joined her in the laboratory. They worked together on the ultrastructure of Dinoflagellate chromosomes, as part of his Finnish thesis. They were the first to spread these chromosomes on water, to collect them on special grids for TEM, to observe them, and to describe their twisted fibrillar organization in the prestigious journal Nature.

For this work, she received in 1974 the Paul Wintrebert Foundation Prize. She delivered several seminars at the Institute of Cytology of the Academy of Sciences of Leningrad (Saint Petersburg). In 1975, the Arago Laboratory acquired a second-hand transmission electron microscope (TEM) which was used until 1982, when it was replaced by a new TEM. It was the first French marine station to have such an apparatus.

At the same time, Marie-Odile Soyer-Gobillard participated in the constitution of a first external team, that of the biochemist Dr. Julio Pudles, to which Prof. André Berkaloff, head of Life Sciences at the CNRS, provided financial support. Their collaboration led to several publications. Thus, the team included Michel Herzog, PhD student, researcher at the CNRS, Françoise de Billy, engineer at the CNRS, Paul Prévot, PhD student of the DEA of biological oceanography, and Yvonne Bhaud, researcher at the CNRS. She became head of the research group Genome and Cell Cycle of Unicellular Eukaryotes.

The observations that Marie-Odile Soyer-Gobillard made with Michel Herzog, biochemist and molecular biologist, allowed her to deepen her knowledge of the organization and composition of DNA and chromatin of dinoflagellates.

Her team has also developed a new research department dedicated to intracellular ecotoxicology, that studied the impact of pollutants, such as heavy metals, organochlorine or organophosphorus pesticides, on marine dinoflagellate protist models.

In 1983, the FRG donated video equipment for the Arago Laboratory. It provided many services by allowing the permanent researchers to develop new lines of research.

The reputation acquired by the team enabled it to obtain funds to organize various national, European and world congresses in the fields of protistology and cell biology. Thus, in June 1983, the 5th meeting of the International Society for Evolutionary Protistology (ISEP) was held in Banyuls-sur-Mer.

In 1984, she became Director of Research and Director of the Cell and Molecular Biology Department at the laboratory of Banyuls-sur-Mer.

In 1988, Marie-Odile Soyer-Gobillard's work was awarded with the Trégouboff prize by the National Academy of Sciences (NAS).

In 1990, she succeeded in demonstrating the co-localization of two DNAs (B and Z DNAs) by electro-immunolocalization to explain the functioning of permanently compacted chromosomes in a dinoflagellate. Eric Perret, a new PhD student, arrives at the laboratory for his thesis on the study of cell division in the dinoflagellate Crypthecodinium cohnii. Many results were obtained, including the discovery of several proteins playing a major role in the mitotic process, some of which have been conserved from dinoflagellates to humans.

Since 1985, the laboratory has acquired the necessary equipment for the development of electro-immunocytochemistry techniques. The technique of vitrification of biological material at ultra-low temperature allowed the team to localize the proteins from which the genes have been isolated and the antibodies produced. This was the first time this cryopreservation technique has been used in a marine station. A confocal microscope and a third generation TEM completed the equipment.

In 1991, Marie-Odile Soyer-Gobillard co-supervised, with André Picard, a specialist in the molecular regulation of the cell-cycle, the thesis of Michèle Barbier, a new doctoral student. The aim of this work was to study the specific molecules that regulate the cell-cycle in unicellular dinoflagellate eukaryotes. With Michèle Barbier and Muriel Audit, she demonstrated the presence and immunolocalized the unique cyclin B (p56cdc13) that controls the life cycle of the yeast Saccharomyces pombe.

At the same time, Jérôme Ausseil, freshly arrived at the Laboratory as part of a thesis, managed not only to isolate cell division proteins in dinoflagellates, to make antibodies, to immunolocalize them at the ultrastructural scale, but also to research the interrelations of these motor proteins.

In 1996, Hervé Moreau, a cell and molecular biologist, joined Marie-Odile Soyer-Gobillard's team. In 2000, he started working on another unicellular model, that of chlorophytes (Prasinophyceae), more precisely Ostreococcus tauri, the smallest known eukaryotic chlorophyll protist, whose genome was sequenced in 2006, opening the way to a new science calledenvironmental genomics.

After her retirement in 2000, the dinoflagellate protist model was no longer used at the Arago Laboratory. However, it is still studied in many laboratories around the world. Marie-Odile Soyer-Gobillard continues to defend this original model. She received the distinction of Emeritus from the CNRS from 2000 to 2005.

Within the association Hhorages-France
Since 2015, the Hhorages cohort has been registered at the Epidemiological Portal of French Health Databases INSERM (French National Institute of Health and Medical Research), as well as at AVIESAN (National Alliance for Life Sciences and Health). The developed questionnaire, accepted by the National Commission on Informatics and Liberty (CNIL), was sent to the families, and the answers synthesized.

The meticulous analysis of the data allowed Marie-Odile Soyer-Gobillard, with the Sultan and Courtet teams of the Montpellier University Hospital, to demonstrate that prenatal exposure to artificial estrogens (DES and/or ethinylestradiol) is clearly associated with a high risk of severe psychiatric disorders in adolescence or post-adolescence. These disorders may be accompanied by somatic disorders such as genital malformations or cancers.

In 2007, Marie-Odile Soyer-Gobillard met with Professor Marie-Odile Krebs, a psychiatrist, professor and researcher at the Sainte-Anne Hospital Center of The Institute of Psychiatry and Neuroscience of Paris (INSERM U894), in order to submit this hypothesis. Together, they set up a research project Institutional-Citizen Partnership for Research and Innovation (PICRI) entitled "Influence of hormonal treatments on brain development during pregnancy: study of phenotypic, psychiatric, behavioral and biological changes in informative families", which enabled them to obtain initial funding from the Île-de-France Region.

Prof. Krebs' team, with Dr. Oussama Kébir, a psychiatrist and molecular biologist leading the molecular research part, started to analyze the data collected by Hhorages, then gathered pre-existing epidemiological studies on the subject, before looking at epigenetics – an emerging science at the time – as a plausible explanation for the appearance of psychiatric disorders in people who had been exposed in utero to DES. This research resulted in a publication in The World Journal of Biological Psychiatry in 2012.

At the 2007 International Congress of French Language Psychiatry and Neurology, she presented to a hundred or so psychiatrists and neurologists one of the avenues of research on the causes of schizophrenia, while arguing the problem of Hhorages and the research work in progress carried out by her team at the Sainte-Anne Hospital Center in collaboration with the association's families.

In 2011, with the endocrinology team of the Montpellier University Hospital led by Prof. Charles Sultan, Marie-Odile Soyer-Gobillard participated in the demonstration of the transgenerational effect – on male grandchildren – of the use of DES during pregnancy on the presence ofhypospadias (a malformation of the male genital tract), which led to a publication in the renowned American journal Fertility and Sterility. In this work, the authors showed that the rate of hypospadias is twice as high as in DES sons.

On the occasion of a broadcast on the French TV channel M6, she announced that her report will be submitted to Afssaps. On January 21, 2011, 6 members of Hhorages were received by the Afssaps pharmacovigilance commission. In 2015, following the analysis of data from 529 families, she demonstrated, with Prof. Sultan (Endocrinologist) and Prof. Courtet (Psychiatrist), that more than 740 exposed children suffered from psychiatric disorders, and that 6% of the children born after a previous exposure – i.e. after a pregnancy treated with DES – also suffered from psychiatric disorders, while the non-exposed children did not suffer from any disorder. These include eating disorders, depression, bipolar disorders, schizophrenia, suicide attempts and suicides, with rates much higher than in the general population. Their findings were published in the journal Gynecological Endocrinology.

In 2017, from analyses of Hhorages siblings, the Krebs team highlighted in exposed patients suffering from psychotic disorder differential specific methylated regions: in the zinc finger protein gene ZFP57 and in the ADAMTS9 gene promoter. The ZFP57 gene, located on chromosome 6, is a transcriptional regulator of many genes affecting neurodevelopment and neuroplasticity. The ADAMTS9 gene is involved in the control of organ shape, particularly of the reproductive organs, which are often malformed following DES exposure. ADAMTS9 is also involved in the development of the central nervous system as well as in various types of cancers. This study was published in PlosOne, following which Inserm issued a press release.

Since 2015, Marie-Odile Soyer-Gobillard also wondered about the effects of synthetic progestins and proposed to Prof. Sultan that it should be studied. She then identified the mothers of the Hhorages cohort who were treated only with this type of hormone as well as the disorders of the exposed children. In 2019, Marie-Odile Soyer-Gobillard, together with Prof. Sultan's team, demonstrated the psychiatric effects of synthetic progestins in a publication. Comparing the results, we see that they are similar to those of the 2015 study on synthetic estrogens, diethylstilbestrol and ethinylestradiol. In 2020, with the Montpellier team, she reported a case of an 8-year-old girl, a DES Granddaughter (whose grandmother received DES therapy during pregnancy), who had primary clear cell carcinoma of the cervix, a very rare type of cancer often linked with DES exposure. The French newspaper La dépêche devoted an article to this. That same year, another study showed that 11 grandsons of women treated with diethylstilbestrol during pregnancy had idiopathic partial androgen insensitivity syndrome.

While browsing the scientific literature, Marie-Odile Soyer-Gobillard discovered a Chinese study by Prof. Paul Yao that caught her attention. He detected a hyper-methylation of an estrogen receptor, the Erβ gene promoter, in the amygdala area of the brain of mice exposed to a progestin, and demonstrated that this leads to autism-like behavior in the offspring. Marie-Odile Soyer-Gobillard then contacted Prof. Yao's team to collaborate. She published with Charles Sultan, Laura Gaspari and Paul Yao in 2021 in "Factors affecting Development" (Academic Press) an invited chapter, as well as an article in the French medical journal Pratiques dealing with Hhorages' and Prof. Yao's findings.

In 2021, Marie-Odile Soyer-Gobillard and Prof. Sultan's team published a case study carried out in an informative family of the Hhorages cohort. They report that DES, prescribed for 3 months to a mother after each of her 11 deliveries to inhibit lactation, had consequences on all her children, except the first one – not exposed and then serving as a control. They suffer from psychiatric disorders and, for the most part, somatic disorders as well – including endometriosis and hypospadias. In her grandchildren, in the 3rd generation, they report several cases of autism, psychiatric disorders, as well as endometriosis and hypospadias. This is the first time that a study found a high rate of psychiatric disorders in two or even three generations in the same family, including DES-exposed pregnancies and a DES-free pregnancy.

Also in 2021, Marie-Odile Soyer-Gobillard, Laura Gaspari, Charles Sultan et al. showed that prenatal exposure to DES contributes to the development of endometriosis in exposed daughters, but also in granddaughters, illustrating the multi-generational effect of DES.

Preliminary work, still in progress with the Hhorages cohort, highlights cases of gender dysphoria (transgender). It was presented in 2016 at the Practical Gynecology and Obstetrics Conference in Paris. Marie-Odile Soyer-Gobillard continues to alert on the dangers of artificial sex hormones, including the contraceptive pill, on those of Bisphenol A (BPA) – a widely used plasticizer whose chemical composition is similar to DES – pesticides, such as DDT or chlordecone, organophosphate compounds – toxic to the nervous system. In 2018, at the Third International Meeting on Environmental Health, Strasbourg Council of Europe, then in 2021 at the 4th Congress of Environmental Medicine in Fort-de-France (Martinique), she declared: "Environmental endocrine disruptors are one of the keys to explain the unprecedented growth of chronic diseases. This is a hopeful avenue to curb their progression and regain control of health expenditures", and, referring to the fact that the transgenerational effect of DES has been demonstrated up to 8 generations for cancer in mice : "The transgenerational effect of DES constitutes a real time bomb".

Scientific papers
To date, Marie-Odile Soyer-Gobillard has published more than 180 publications in international peer-reviewed scientific journals, particularly in cell and molecular biology, and has given more than 200 presentations at conferences, ,.

Books

 * Margulis L., M.O. Soyer-Gobillard & J. Corliss, Evolutionary protistology. The organism as cell. Rep. Origins of Life, 1984, 13 (3-4). D.Reidel Publishing Company, Dordrecht/Boston, 183 pp (ISBN 9789027717658).
 * Soyer-Gobillard, M.O. & Schrevel, J, The Discoveries and Artistic Talents of Édouard Chatton and André Lwoff, Famous Biologists. (Bilingual version, French-English). Cambridge Scholars Publishing (CSP) Editor, June 2020. (283 pp., 123 Figs) (ISBN 978-1-5275-5066-7).
 * Testimonial (in French): Une résilience ou les trois Marie-Odile, Nombre 7 Editions, 2021 (ISBN 9782381536606)

Artworks
In October 1998, after the death of her son, she started working with clay in a workshop in Perpignan. In 2000, she became a sculptor and held her first exhibition in Banyuls-sur-Mer, the homeland of Aristide Maillol. In 2013, she declares "I had lived the ignoble, and I wanted to recreate beauty".

Her work has been exhibited on numerous occasions, notably in Paris, Perpignan, Barcelona and Sézanne. In September 2000, she received the 3rd international prize of Sculpture at the International Art Fair of Argèles-sur-Mer.

Selected media

 * In January 2000, Brigitte Bègue, journalist at the French mutualist magazine Viva, wrote the first article in France on psychiatric disorders linked to in utero exposure to DES: "Va-t-on vers un nouveau scandale du Distilbène ?" ("Are we heading for a new Distilbène scandal?"), in which Marie-Odile Gobillard-Soyer testified.
 * In 2002, a Catalan journalist from Barcelona, A. Milian, published in the newspaper El temps "Condemnats abans de néixer : Hormones sota sospita." ("Condemned before birth: Hormones under suspicion"), an article in which she also testified . That same year, Jennifer Margulis, an American journalist and writer, published an article in the same newspaper entitled "Hormones artificials i fills amb problemes psiquics." ("Synthetic hormones and children with mental disorders").
 * In 2004, Brigitte Bègue published again in Viva "Le Distilbène a détruit leur vie" ("Distilbene ruined their lives") the testimonies of Mauricette Puillandre and Marie-Odile Gobillard-Soyer.
 * In July 2006, Marie-Odile Soyer-Gobillard gave an interview to the French magazine Profession Sage-femme
 * In 2008, she was interviewed on the Les pieds sur terre program on France Culture.
 * In 2011, another article entitled "Une mère contre le Distilbène" ("A mother against Distilbene") is dedicated to her in the magazine Viva.
 * In 2012, she participated in the film-investigation of Radio télévision Suisse (RTS) in the program Magasine Santé 36.9 entitled: "Distilbène® : un héritage empoisonné" ('Distilbène®: a poisoned legacy").
 * In 2021, for her nomination to the rank of Chevalier de la Légion d’Honneur, the daily newspaper L’indépendant devoted an article to her, as well as the Journal l’Union of Reims.

Awards and honors

 * In 1974, Marie-Odile Soyer-Gobillard received the Paul Wintrebert Foundation Prize
 * In 1988, she received the Trégouboff Prize of the National Academy of Sciences (quadrennial marine biology prize).
 * From 2000 to 2005, she was Emeritus Research Director at the CNRS.
 * From 2004 to 2009, she was a corresponding member of the National Museum of Natural History (MNHN) of Paris.
 * On July 14, 2021, on the occasion of the Bastille Day, she was appointed Chevalier de la Légion d'Honneur, in recognition of her scientific and associative career