Reproductive tract biology: Of mice and men

Abstract

The study of male and female reproductive tract development requires expertise in two separate disciplines, developmental biology and endocrinology. For ease of experimentation and economy, the mouse has been used extensively as a model for human development and pathogenesis, and for the most part similarities in developmental processes and hormone action provide ample justification for the relevance of mouse models for human reproductive tract development. Indeed, there are many examples describing the phenotype of human genetic disorders that have a reasonably comparable phenotype in mice, attesting to the congruence between mouse and human development. However, anatomic, developmental and endocrinologic differences exist between mice and humans that (1) must be appreciated and (2) considered with caution when extrapolating information between all animal models and humans. It is critical that the investigator be aware of both the similarities and differences in organogenesis and hormone action within male and female reproductive tracts so as to focus on those features of mouse models with clear relevance to human development/pathology. This review, written by a team with extensive expertise in the anatomy, developmental biology and endocrinology of both mouse and human urogenital tracts, focusses upon the significant human/mouse differences, and when appropriate voices a cautionary note regarding extrapolation of mouse models for understanding development of human male and female reproductive tracts.

Organoids of the female reproductive tract

“…On the other hand, although mouse models provide a much more physiologically relevant system, they are not cost effective and many of the human features are not reliably modelled due to considerable species-specific differences in functions of FRT. For example, the endometrium of the mouse does not undergo menstruation and spontaneous decidualisation [ 104 ]. 3D organoid cultures generated from the FRT, a recent advancement for this field, provide solutions to many of the limitations of the available model systems: they can be propagated long-term, function like the tissue of origin and are relatively cost-effective.…”

Etiology of Hypospadias: A Comparative Review of Genetic Factors and Developmental Processes Between Human and Animal Models

“…The mechanism of external genital development, and genetic and environmental factors underlying hypospadias and animal models had been intensively reviewed by different research groups. [7][8][9][10][11] Our knowledge about penile development and hypospadias is mainly based on the studies in animal models. Mice 12 and rats 13 are the most commonly used laboratory animals for hypospadias modeling, in addition, other animals such as guinea pigs, 14 rabbits, 15 and dogs 16 have also been used in hypospadias research.…”

“…The mechanism of external genital development, and genetic and environmental factors underlying hypospadias and animal models had been intensively reviewed by different research groups. 7–11 …”

Development of the external genitalia

“…The paper by Cunha et al sets the stage by describing differences in the adult anatomy and developmental processes in human and mouse external genitalia (Cunha et al, 2019d). Full appreciation of these human-mouse differences requires expertise in anatomy, developmental biology and endocrinology.…”

“…Mouse alpha fetoprotein (AFP) binds estrogens at high affinity and neutralizes estrogen action during the perinatal period, whereas this is not a factor in perinatal humans. This singular fact has profound implications regarding experimental design and interpretation of data as discussed (Cunha et al, 2019d). Nonetheless, mice have been used extensively as a model for development and pathogenesis of human external genitalia, and certain similarities in developmental processes and hormone action provide ample justification for the judicious use of mouse models for https://doi.org/10.1016/j.diff.2019.10.008 human reproductive tract development.…”