All mammals have mammary glands that produce milk, a trait that has fascinated scientists for years. Questions such as why mammary glands evolved in the first place, how they adapted across species, and what unique evolutionary pressures shaped their development remain largely unanswered.
To explore how different species have evolved unique solutions to biological challenges, my team at the Rauner Lab at Tufts University School of Medicine is recreating mammalian diversity in a dish using miniature versions of mammary glands—organoids. These models can shed light on the fundamental biological processes behind milk production, tissue regeneration, and the early stages of breast cancer development.
What are organoids?
Organoids are miniature, 3D structures grown in a cell culture dish that mimic the structure and function of real organs. These models are created by conductive stem cells, which have the unique ability to differentiate into different cell types to form specific organ cell types.
Although they are not exact miniature replicas of full-sized organs, organoids contain enough cells and tissue architecture to recreate the environment and key functions of the organ they are modeling. For example, a mammary gland organoid or breast tissue organoid consists of small elongated ducts that end in a bulbous structure, which mimics the milk ducts and alveoli of the gland tissue.
Organoids are a powerful tool for biomedical research because they provide a 3D representation of an organ’s structure and function. Unlike traditional 2D cell cultures, organoids can mimic the complexity of actual tissues, including their architecture and diverse cell types. This allows researchers to study complex biological processes such as tissue development, regeneration, and disease progression in a controlled environment, while reducing the reliance on animal models.
Mammalian diversity in one dish
Researchers have traditionally used organoids to model human disease, test drugs, and study developmental biology. However, their potential extends far beyond these applications, particularly in the field of evolutionary biology.
My research focuses on generating mammary gland organoids from different mammalian species. Mammals are incredibly diverse, with each species adapted to a wide range of environments and lifestyles. The mammary gland, essential for raising offspring, shows considerable variation between species.
For example, monotremes such as the platypus and echidna belong to a unique and ancient class of mammals. Monotremes split from other mammal groups about 190 million years ago and are distinguished by their reproductive methods: laying eggs rather than giving birth live. Their mammary glands are distinctly different from those of eutherian mammals such as cows and humans, which have nipples; monotremes instead secrete milk through specialized lactiferous hairs.
Scientists believe that different environmental pressures and reproductive strategies have driven the evolution of diverse forms of lactation. However, the exact mechanisms and evolutionary pathways are still largely unknown. By comparing organoids from these diverse species, researchers can shed light on how these ancient structures have evolved and adapted over millions of years to meet the reproductive needs of different animals.
Insights beyond the mammary gland
By studying the unique properties of the mammary gland, we can also gain insight into other areas of biology and medicine.
For example, the mammary gland can regenerate with each cycle of reproduction and lactation, making it an excellent model for studying tissue regeneration. Organoids allow researchers to observe the process of regeneration in real time and explore how different species have evolved to maintain this regenerative capacity. Understanding the mechanisms behind regeneration could lead to advances in regenerative medicine, a field that focuses on repairing or replacing damaged tissues and organs in conditions such as heart disease, diabetes, and injury.
Breast organoids may also aid in breast cancer research. Studying breast organoids from species that rarely develop breast tumors, such as cows and pigs, could reveal potential protective mechanisms and provide new strategies for preventing and treating breast cancer in humans. Organoids also provide a platform to study the early events of tumor formation and the cellular environment that contributes to cancer development.
Organoids also allow scientists to study the initiation, duration, and termination of lactation in different species. The lactation process varies greatly among mammals, influenced by factors such as hormonal changes and environmental conditions. Some mammals have unique forms of lactation. For example, marsupials such as the tammar wallaby can produce two types of milk simultaneously to meet the nutritional needs of offspring at different developmental stages, a phenomenon known as asynchronous simultaneous lactation. Furthermore, the fur seal can maintain lactation despite extended periods without suckling.
By studying different types of lactation using mammary gland organoids, we can gain more insight into how lactation is regulated. In this way, we can discover evolutionary adaptations that can clarify the biology of human lactation and improve strategies for livestock milk production in agriculture.
The potential of organoid technology
Organoids offer several advantages over traditional animal models. First, they provide a controlled environment to study complex biological processes and allow scientists to perform multiple tests simultaneously, increasing the efficiency of research.
They also reduce the ethical concerns associated with animal testing. Organoids can be generated from animals that are not available for living research, such as rare or endangered species.
Furthermore, organoids can be genetically modified to investigate specific genes and pathways, providing deeper insights into the molecular mechanisms underlying mammary gland biology.
While organoids are a powerful tool, they do have limitations. They cannot fully mimic the complexity of living tissues, and findings from organoid studies must be validated in living subjects. Despite these obstacles, advances in organoid technology continue to push the boundaries of what is possible, and provide new opportunities to explore mammalian diversity and evolution.
By recreating the diversity of mammalian tissues in a dish, researchers can gain important insights into how different species have evolved to solve biological challenges, potentially benefiting human health, agriculture, and food science.
This article is republished from The Conversation, a nonprofit, independent news organization that brings you facts and reliable analysis to help you understand our complex world. It was written by: Gat Rauner, Tufts University
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Gat Rauner received funding from the Department of Defense Breast Cancer Research Program