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Mammary glands on a plate – what miniature organs reveal about evolution, lactation, regeneration and breast cancer

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All mammals have mammary glands that produce milka feature that has fascinated scientists for many years. Questions such as why mammary glands evolved in the first place, how they adapted to different species, and what unique evolutionary pressures shaped their development remain largely unanswered.

To investigate how various species have developed unique solutions to biological challenges, my team node Rauner Laboratory from Tufts University School of Medicine is recreating mammal diversity on a plate through miniature versions of mammary glands – organoids. These models can clarify fundamental biological processes behind milk production, tissue regeneration and the early stages of breast cancer development.

What are organoids?

Organoids are miniature and 3D structures grown in a cell culture dish that mimics the structure and function of real organs. These models are made by guiding stem cells, which have the unique ability to differentiate into multiple cell types, to form specific types of organic cells.

Although they are not exact miniature replicas of full-size organs, organoids contain enough cells and tissue architecture to recreate the environment and primary functions of the organ they model. For example, a mammary gland organoid or a breast tissue organoid they are composed of tiny elongated ducts that end in a spherical structure, mimicking the milk ducts and alveoli of gland tissue.

Diagram representing the generation of organoids from breast tissue
Breast organoids mimic the structure and function of real tissues. Gat Rauner/Created with BioRender.com, CC BY-SA

Organoids provide a powerful tool for biomedical research because they offer a 3D representation of an organ’s structure and function. Unlike traditional 2D cell cultures, organoids can mimic the complexity of real 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 dependence on animal models.

Diversity of mammals on a plate

Researchers have traditionally used organoids to model human diseases, test drugs and study developmental biology. However, its potential goes far beyond these applications, particularly in the field of evolutionary biology.

My search focuses on generating mammary gland organoids from a variety of mammalian species. Mammals are incredibly diverse, with each species adapted to a wide variety of environments and lifestyles. The mammary gland, essential for nourishing offspring, exhibits significant variation between species.

Four microscopy images arranged in a square, each with globular-shaped cells stained in magenta and tealFour microscopy images arranged in a square, each with globular-shaped cells stained in magenta and teal

For example, monotremes, such as the platypus and echidna belong to a unique and ancient class of mammals. Monotremes diverged from other groups of mammals approximately 190 million years ago and are distinguished by their reproductive methods: laying eggs rather than giving birth alive. Their mammary glands are markedly different from those of eutherian mammals, such as cows and humans, which have nipples; instead, monotremes secrete milk through specialized mammary hairs.

Scientists believe that different environmental pressures and reproductive strategies drove the evolution of different 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 evolved and adapted over millions of years to meet the reproductive needs of different animals.

Insights beyond the mammary gland

Studying the unique properties of the mammary gland can also shed light on other areas of biology and medicine.

For example, the mammary gland is capable of regenerate every cycle reproduction and lactation. This makes it an excellent model to study tissue regeneration. With organoids, researchers can observe the regeneration process in real time and investigate how different species have evolved to maintain this regenerative capacity. Understanding the mechanisms behind regeneration could lead to advances in regenerative medicinean area that focuses on repairing or replacing tissues and organs damaged in conditions such as heart disease, diabetes, and injuries.

Breast organoids can also help with breast cancer to look for. Studying mammary organoids of species that rarely develop breast tumorslike cows and pigs, could discover potential protection mechanisms and inform new strategies for preventing and treating breast cancer in people. 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 cessation of lactation in different species. The lactation process varies widely among mammalsinfluenced by factors such as hormonal changes and environmental conditions. Some mammals have unique forms of lactation. For example, marsupials like Tammar Kangaroo can produce two types of milk simultaneously to meet the nutritional needs of offspring at different stages of development, a phenomenon known as asynchronous simultaneous lactation. Furthermore, the seal can maintain lactation despite long periods without breastfeeding.

Studying different types of lactation through mammary organoids can provide deeper insights into how lactation is regulated, revealing evolutionary adaptations that could clarify the biology of human lactation and improve livestock milk production strategies in agriculture.

The potential of organoid technology

Organoids offer several advantages over traditional animal models. On the one hand, they provide a controlled environment to study complex biological processes and allow scientists to perform multiple tests simultaneously, increasing search efficiency.

They also reduce ethical concerns associated with animal research. Organoids can be generated from animals that are not available for live searchas rare or endangered species.

Furthermore, organoids can be genetically modified to probe specific genes and pathways, providing deeper insights into the molecular mechanisms underlying mammary gland biology.

Although organoids are a powerful tool, they are not without limitations. They cannot fully replicate the complexity of living tissues, and results from organoid studies must be validated in living subjects. Despite these obstacles, advances in organoid technology continue to push the limits of what is possible, offering 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, with the potential to benefit human health, agriculture and nutrition science.

This article was republished from The conversationan independent, nonprofit news organization that brings you trusted facts and 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



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