The HipGametes consortium consists of a multidisciplinary team of Dutch experts aiming to develop in vitro gametogenesis (IVG) protocols for female (mature oocytes) and male (sperm cells) starting from (edited) hiPSCs and exploring the ethical, legal, and societal implications of using stem cell-derived gametes to generate (non-viable) human embryos.

This collaboration involves the Leids University Medical Center (LUMC), Amsterdam University Medical Center (AMC), Erasmus Medical Center (EMC), Maastricht University (UM), and Rathenau Institute (RI).

The consortium members are experts in in vitro gametogenesis (Chuva de Sousa Lopes (LUMC), Hamer (AMC), Baarends (EMC)), human reproduction (van Pelt (AMC), Chuva de Sousa Lopes (LUMC)), embryo models (Geijsen (LUMC), Gribnau (EMC)), as well as the ethical (Pereira Daoud, de Wert (UM)), legal (Spaander, Ploem (AMC)), and societal (Verra, Harmsen, Habets, Edelenbosch (RI)) aspects of human reproduction and human embryo modeling.

Meet our team

More information about: Susana Chuva de Sousa Lopes

Susana Chuva de Sousa Lopes

Professor, Leiden University Medical Center

Susana is Full Professor Human Developmental Biology at the Dept Anatomy and Embryology, LUMC and appointed Guest Professor at the Dept. Reproductive Medicine, University Ghent, Belgium from 2013. She investigates in vivo human development and in parallel develops in vitro human differentiation assays from pluripotent stem cells. She has a strong knowledge of single-cell technologies, computational biology and genome editing. She is mainly focused on the urogenital system, in particular the germ cells, and how the (epi)genetic information is transmitted from generation to generation. She is engaged in the development of assays leading to the maturation of oocytes from ovarian material (artificial ovaries) and in vitro gametogenesis. She has generated both human embryonic stem cells and induced pluripotent stem cells. Her research is relevant to determine novel strategies for fertility preservation and develop innovative technologies in human reproduction. Her group currently investigates the composition dynamics of the human fetal and adult ovary at the single-cell level and is developing strategies to mature oocytes in vitro in artificial follicles. Moreover, she investigates how the sex chromosomes (XX and XY) influence the differentiation potential of male and female pluripotent stem cells during in vitro gametogenesis.

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More information about: Willy Baarends

Willy Baarends

Associate Professor, Erasmus MC University Medical Center

Willy is in the Dept of Developmental Biology (EMC) and currently supervises 5 PhD students, one technician, and a MSc student. Her group has made major contributions to the understanding of the mechanism of XY body (special chromatin configuration of the sex chromosomes) formation during male meiotic prophase. She identified the role of persistent meiotic DNA double-strand breaks (DSBs) in the mediation of meiotic transcriptional silencing which is key to formation of the XY body. Subsequently she has broadened this research question towards trying to unravel how meiotic DSB repair and chromosome pairing are mechanistically connected. Her group was the first to use two-colour super-resolution (dSTORM) technology to study the repair foci in meiotic prophase to show that two key proteins involved in the repair process form complicated structures in a much more variable fashion than would be expected and predicted based on genetic data and ‘omics’ approaches. Using her microscopy expertise she also developed a useful phenotyping protocol to assess meiotic defects in men suffering from nonobstructive azoospermia, and could classify the most frequent meiotic arrest stages. She has sequenced the genome of Ellobius lutescens as a first step towards unravelling the sex determination pathway in this enigmatic species with karyotype 17,X in both sexes.

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More information about: Corrette Ploem

Corrette Ploem

Appointed Professor, University of Amsterdam

Corrette is associate professor of health law, working at the Amsterdam University Medical Center (before she worked for 7 years as a program manager at ZonMw) and special appointed professor of Law, Health Care Technology and Medicine because of the Royal Dutch Medical Association (Faculty of Law, University of Amsterdam). Although she is active in the wider field of health law, she especially contributes on topics as human subject research, reproductive technologies, privacy and genetics. She wrote a PhD thesis on the legal privacy aspects of data research (published in 2004) and participated in many (interdisciplinary) research projects. She is a member of the Dutch Health Council, the Central Committee for Human Subject Research and other review boards, and the editorial board of the Dutch Journal of Health Law. Currently, she is involved in projects regarding the evaluation of health laws and the legal/ethical aspects of personalized medicine. Over the years, she performed several multidisciplinary research projects, also on issues that are closely related to the PSIDER-research program. Corrette has a broad field of scientific interest, but, together with ethicists and empirical researchers, she also carried out research on the specific topic of embryo research and the closely related to the Dutch Embryo Act. Ploem, together with Dondorp and others, just finished the third evaluation of the Embryonic Act (2020). From 2017-2019 she carried out two other evaluation studies (Law on human subject research and Abortion Act). She also participated on a project on the legal/ethical aspects of personalized medicine (2018-2020). From 2016-2018 she was involved in the TANGO project, on personalized medicine in oncology. Furthermore, she wrote a report on the legal aspects of data and tissue research and biobanks in commission of the Dutch Association for Health Law. One of the issues addressed in this report concerns ownership of tissue. On that topic she also wrote a review of a first official proposal of the Dutch government (2018), regulating ‘further use’ of human tissue.

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More information about: Geert Hamer

Geert Hamer

Associate Professor, Amsterdam UMC

Geert studied DNA damage repair and apoptosis in spermatogenesis during his PhD and his research still focuses on genome stability maintenance and development of germ cells. He was part of the team that published the first transcriptome of adult human male germ cells. This formed the basis for a novel research line on the role of germ cell-specific genes in the development and treatment of cancer. Moreover, his expertise also entails oocytes and early human embryology. For instance, his team recently discovered a miRNA that is specifically secreted by, and aids implantation of, good quality (euploid) human embryos and found that aging oocytes suffer from mitochondrial dysfunction. Geert has also unravelled two separate mechanisms that lead to human meiotic arrest and investigated the changing DNA damage response during spermatogonial differentiation using CRISPR-CAS and in vitro male germline stem cell culture systems. Geert is actively involved in mimicking the somatic male gonadal niche of Sertoli cells and how that directs spermatogenesis, and has recently started to use human induced pluripotent stem cells as in vitro models to study male gametogenesis and is particularly interested in meiotic progression. Geert is regularly invited as speaker on science symposiums for clinicians or lay-men, panel discussions and public debates. He is BKO certified and teaches in many courses for medicine, biology or medical biology (undergraduate and PhD) students.

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More information about: Ana Pereira Daoud

Ana Pereira Daoud

Assistant Professor, Maastricht University

Ana's research focusses on exploring the ethical ramifications of stem cell-derived gametes (SCDGs) and contributing to the development of tangible guidelines, capable of harnessing the potential of SCDGs as valuable research tools, whilst remaining conscientious of morally and legally acceptable practices.

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More information about: Ans van Pelt

Ans van Pelt

Professor, Amsterdam UMC

Ans is Professor Translational Reproductive Medicine at the AMC, and expert in human spermatogonial stem cell (SSC) isolation and culture. She has an interest in understanding how the SSC remain undifferentiated in culture, but also how they could be differentiated correctly to mature spermatozoa, so that SSC could either be used for transplantation purposes or to develop personalised disease models in vitro to study (male) infertility. During her PhD period she worked on male reproduction, specifically on SSC and was the first to show that retinoids are important for their differentiation towards sperm. She established an isolation method for spermatogonia and investigated self-renewal and differentiation of SSC in vitro. In 2007, she moved to the AMC to continue her research on human SSC and future use for clinical fertility treatments. Under her supervision the first transcriptome of adult human male germ cells throughout spermatogenesis was generated as well as the first in vitro system to propagate human SSC from adult and prepubertal human testis.

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More information about: Callista Mulder

Callista Mulder

Assistant Professor, Amsterdam UMC

Callista has 10+ years of experience in spermatogenesis and novel stem cell based fertility treatments, with a focus on Spermatogonial Stem Cells (SSCs) and the testicular somatic niche. She is actively involved in establishing hiPSC derived male gonadal somatic niche to support hiPSC germ cell development. Callista’s main research focus over the past 5 years has been the preclinical development of fertility preservation and restoration therapies for those who do not produce sperm and cannot have a biologically own child otherwise, including (childhood) cancer survivors, patients with benign hematological disorders, transwomen and intersex individuals. She focusses on stem cell-based fertility treatments, specifically centered around SSCs, the cells that have the capacity to develop into sperm upon puberty. She was the first to investigate the long-term health for both recipients and offspring of SSC transplantation in a mouse model. In addition, she took part in a project showing that testicular organ cultures of different mouse strains have a diverse differentiation potential. Callista contributed to a large cohort study that proved the presence of spermatogonia in a majority of transwomen, thereby opening up new fertility preservation strategies for them. She is currently investigating the circadian rhythm in sperm formation, funded through a personal ZonMW Off Road grant. Moreover, Callista is BKO certified, coordinates master education on reproductive biology and medicine at the University of Amsterdam, and teaches BSc students at the Vrije Universiteit Amsterdam. She supervises many BSc and MSc students and is currently co-promotor of 4 PhD students.

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More information about: Ilse de Bruin

Ilse de Bruin

PhD Candidate, Erasmus MC University Medical Center

I obtained my Bachelor Nanobiology and Master Nanobiology at TU Delft & Erasmus MC (joint degree). During my masters final project, I did the internship at the Department of Developmental Biology at Erasmus MC, where I looked into mouse X chromosome reactivation using reporter cell lines, and making cell lines to be able to study human X chromosome inactivation. During this period, I got fascinated by early mammalian development and realized I wanted to continue my PhD in this field. The HipGametes project thus fits my interest, even more so because it’s a project with collaborators, not only with other biomedical scientists but also with researchers involved in ethics, legislation and societal studies. Besides Nanobiology, I’m interested in education and really like teaching. I followed the Master Science Education and Communication at TU Delft, and obtained first-degree qualifications for teaching mathematics to high school students. During my PhD so far, I’ve been involved in various bachelor courses, both as teaching assistant in class as well as optimizing the course content. In HipGametes, I am involved in work package 3, female in vitro gametogenesis. The goal is to in vitro differentiate human induced pluripotent stem cells into mature oocytes. This would enable us to study meiosis, (epi)genome regulations and cell-cell signaling. A special interest lies in the dynamics of the X chromosomes during this process.

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More information about: Madalena Vaz Santos

Madalena Vaz Santos

PhD Candidate, Amsterdam UMC

Project name: In-vitro spermatogenesis from induced pluripotent stem cells I will work on the development of an in-vitro culture system for human spermatogenesis. The project will focus on the generation of primordial germ cells from hiPSCs, that will subsequently be co-cultured with a feeder layer originating from human somatic testicular cells, fibroblast feeder layer or human Sertoli-cell lines (existing or also induced from hiPCSs) to induce differentiation through meiosis and spermiogenesis and complete hiPSC-derived human spermatogenesis. I have a BSc Biology (specialization in evolutionary and developmental biology) and MSc Human and Environmental Biology (specialization in human biology) from the University of Lisbon. I have also completed a research internship on the characterization of rosette stem cells in the mouse early-embryo development in the lab of Derk ten Berge at the Erasmus MC University Medical Center.

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More information about: Joost Gribnau

Joost Gribnau

Professor, Erasmus MC University Medical Center

Joost is full professor and head of the department of Developmental Biology at the Erasmus MC. He also founded the Erasmus MC iPS core facility in 2010, which has so far generated more than 250 patient iPS cell lines providing the basis for a wealth of research at the Erasmus MC. In addition, the Gribnau laboratory has established technology to readout epigenomic, transcriptomic and enhancer changes directing cell fate decisions, that is currently applied to define better culture conditions for directed iPSC differentiation. Joost has a longstanding interest in understanding regulation of gene expression in relation to cell fate decisions in development and cell differentiation. Initial studies focused on different aspects of the X-chromosome inactivation (XCI) process, that inactivates one X chromosome in every female cell. The Gribnau laboratory unravelled many key steps of the mechanism directing initiation of XCI (Monkhorst et al., Cell 2008, Jonkers et al., Cell 2009, Barakat et al., Mol Cell 2015,Gontan et al., Nature 2012 and Nature comm. 2018). Recent work focusses on the identification of new XCI regulatory factors (van Bemmel et al. Nat Genet. 2019). To study epigenetic changes in development, the Gribnau laboratory developed several new technologies including MeD-seq and DCM-TM to determine genome wide DNA methylation profiles (MeDseq) and retrieve gene and enhancer activity maps of past expression (DCM-TM) (Boers Genome Res. 2018, submitted). These form the basis for more than 50 collaborations worldwide. The technology has been licensed to Methylomics B.V., that applies the MeD-seq for marker discovery studies in cancer. The Gribnau laboratory has published many papers on human disease modelling using iPSCs, and knowledge obtained is translated and implemented into the iPS facility. At present the group focuses on understanding cell signalling directing cell fate decisions to be translated to improved iPSC differentiation protocols.

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More information about: Mathangi Lakshmipathi

Mathangi Lakshmipathi

PhD Candidate, Amsterdam UMC

Project name: Generation of a human induced pluripotent stem cells (hiPSC)-derived testicular somatic niche to support in vitro human spermatogenesis The project will focus on the generation of hiPSC-derived somatic cells in the germ cell niche (including Sertoli-like cells), and characterization of the derived cells. The final aim is to co-culture the hiPSC derived somatic cells with germ cells, to direct germ cell differentiation into the male direction to support in vitro spermatogenesis. Mathangi is a second year PhD candidate at the Reproductive Biology laboratory (LVV) at Amsterdam UMC. Since her Bachelor’s education in Biotechnology from SRM University, India, she has a consistently good track record. She carried out her bachelor’s thesis at the Harvard-MIT-HST, USA in the Immuno-engineering Research Laboratory, where she designed chimeric nanoparticles for modulating macrophages in the cancer microenvironment. After obtaining her Bachelor’s degree, she came to the Netherlands to pursue her Master’s degree at the Wageningen University and Research (WUR). At WUR, she was a part of three different labs, for an internship and two theses. She carried out her first internship at the Laboratory of Molecular Biology, where she constructed tools required for plant-orthology studies in C.mimosoides and symbiotic assays in M. truncatula. Following this, she completed two theses at the Human and Animal Physiology Laboratory, where she studied the effects of IL-6 on mitochondrial dynamics in skeletal muscle in cancer-induced cachexia and the consequences of c-kit mutations on fertility in young Witrik cattle, respectively. Currently, her PhD project focuses on the development of an induced pluripotent stem cells (iPSC)-based culture system to model in vitro spermatogenesis. The purpose of developing such a system would be to comprehend the developmental process of the gonads and its somatic niche, and thereby be able to identify factors responsible for infertility or other disorders of sex development (DSD).

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More information about: Merel Spaander

Merel Spaander

PhD Candidate, University of Amsterdam

Project name: Ethical and legal aspects of non-viable embryos from hiPSC-gametes I have an educational background in both neuroscience and (health) law. I obtained my degree(s) at the University of Amsterdam. I am currently teaching and coordinating a course in the Health Law masters at the Law faculty of the University of Amsterdam. The course ‘Legal issues at the beginning and the end of life’ explores the ethical and legal issues regarding sensitive topics at the beginning of life, such as human embryo research and artificial reproductive technologies (e.g. surrogate and homologous insemination), but also at the end of life, such as abortion and euthanasia. My fields of interest have always been on the intersection of biosciences, health law and society. My previous research experience has mostly been on cognitive neuroscience, such as the impact of sleep (deprivation) on the regulation of emotions and the neural correlates of antisocial behavior in youth. In HipGametes, I work on WP6, which explores the legal aspects of non-viable embryos from hiPSC-gametes. What is the (inter)national regulatory system with regard to the development of hiPSC-gametes and what are important legal discussions and developments? In the Netherlands, the Dutch Embryo Act regulates research with human embryos. However, the medical-scientific developments within the field of hiPSC-gametes and the possibility to generate embryos raises new questions about the scope of the Embryo Act. What defines a (human) embryo? How do human embryos and other embryo-like structures (legally) relate to embryos from hiPSC-gametes?

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More information about: Rosanne Edelenbosch

Rosanne Edelenbosch

Senior Researcher, Rathenau Institute

Rosanne is senior researcher and interim coordinator of the health program at the Rathenau Institute. Her main focus is responsible research and innovation (RRI). She has worked on various research themes, including biotechnology, digitalisation, brain science, health systems and food production systems. Rosanne studied Medicine in Leiden. She has a Master's degree in Medical Anthropology & Sociology (UvA) and a Master's degree in Management, Policy Analysis and Entrepreneurship in Health & Life Sciences (VU University). At the Athena Institute she researched and lectured on methods for stakeholder engagement in scientific research. She has been working at the Rathenau Institute since 2016.

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More information about: Simone Harmsen

Simone Harmsen

Researcher, Rathenau Institute

Project name: Societal participation on the topic of hiPSC-gametes and derived non-viable embryos In our project, we will assess the impact of and societal attitudes towards the development of stem cell-derived gametes and the generation of (non-viable) embryos. We will do this via desk-research, focus groups, and the organization of board societal dialogue events in different cities, where we will engage participants in a dialogue to share their perspectives, questions, and considerations with regards to IVG and IVG-embryos. Background Simone is interested in strengthening the dialogue between health science and society. She has expertise in setting up dialogue between scientists, policymakers and citizens from all kinds of backgrounds. How do we equip different target groups with the skills and information they need to engage in constructive conversation? Both her PhD research and her experience as an educational author brought her expertise on this topic. Simone studied Biomedical Sciences, and holds a master's degree in Science Communication. She worked for several years as an educational author and science journalist. Having a desire to delve deeper, she started working as a researcher and lecturer at the Athena Institute at Vrije Universiteit Amsterdam. There she worked on projects that aim to strengthen the perspective of patients in health science and care, for example in youth health care and rheumatology. This work resulted in a thesis on how patient involvement can be anchored in the culture, structure and practice of Dutch health research.

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