Ethical Aspects of Human Embryo Collections: A Historically Grounded Approach to the Blechschmidt Collection at the University of Göttingen

Human body donation and tissue collections are nowadays grounded on a legal framework centered around the concept of informed consent in most countries. Comparable regulations did not exist prior to the second half of the 20th century, when several of the most important collections of human embryos were established. As a particularly prominent example, the Human Embryology Collection (“Blechschmidt Collection”) at the Center of Anatomy, University Medical Center Göttingen, Germany, is described here with regard to how to approach a human specimen collection from the perspective of both collection ethics and the history of science. The methods and concepts used as well as the outcome in terms of historical and ethical knowledge will be discussed as a model for future projects of similar scope at other collection sites. It it also shown that general ethical recommendations published by museum and collection experts are of value only if they are related to profound knowledge about the history of the particular collection in focus.

Reproduction and development

‘Reproduction and development’ opens with the anatomy of the pelvis and perineum, the male and female genital systems, and sexual differentiation, before moving onto reproductive function: the production of gametes in males and females, pregnancy, lactation, the effects of age on reproductive status, and the pharmacology of sex hormones. The other main consideration of this chapter is human embryology, guiding the reader through from fertilization and implantation, gastrulation and germ layer establishment, embryonic folding and body cavity formation, limb, head, and neck development, and development of the major organ systems (including the cardiovascular, gastrointestinal, respiratory, renal, and reproductive systems).

Human Embryogenesis: A Comparative Perspective

Understanding human embryology has historically relied on comparative approaches using mammalian model organisms. With the advent of low-input methods to investigate genetic and epigenetic mechanisms and efficient techniques to assess gene function, we can now study the human embryo directly. These advances have transformed the investigation of early embryogenesis in nonrodent species, thereby providing a broader understanding of conserved and divergent mechanisms. Here, we present an overview of the major events in human preimplantation development and place them in the context of mammalian evolution by comparing these events in other eutherian and metatherian species. We describe the advances of studies on postimplantation development and discuss stem cell models that mimic postimplantation embryos. A comparative perspective highlights the importance of analyzing different organisms with molecular characterization and functional studies to reveal the principles of early development. This growing field has a fundamental impact in regenerative medicine and raises important ethical considerations.

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose

Context The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. Objective The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. Methods We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. Results All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Conclusions Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

Protocol for controlled modeling of human epiblast and amnion development using stem cells

Due to the inaccessibility of post-implantation human embryos and the restriction on in-vitro fertilization (IVF) embryos cultured beyond 14 days, the knowledge of early post-implantation human embryogenesis remains extremely limited. Recently, we have developed a microfluidic in-vitro platform, based on human pluripotent stem cells (hPSCs), which is capable of recapitulating several key developmental landmarks of early human post-implantation embryonic development, including lumenogenesis of the epiblast (EPI), amniogenesis, and specification of primordial germ cells (PGCs) and of primitive streak (PS) cells. Given its controllability and reproducibility, the microfluidic platform provides a powerful experimental platform to advance knowledge of human embryology and reproduction. This protocol describes the preparation of the microfluidic device and its implementation for modeling human post-implantation epiblast and amnion development using hPSCs.