# Developmental basis of male nipple loss and retention in mammals

## TL;DR

The study explains why some male mammals, like mice, lose their nipples while others, like humans, retain them, based on differences in hormone signaling during development.

## Contribution

The study identifies the role of androgen receptor presence in mice versus its absence in guinea pigs during sexual differentiation in determining nipple retention or loss.

## Key findings

- Androgen receptor (AR) is present in mouse mammary glands, leading to nipple atrophy via apoptosis and autophagy.
- Guinea pigs lack AR during development, resulting in Wnt pathway activation and nipple formation.
- Testosterone's effect on nipple development depends on AR presence in the species.

## Abstract

Most male mammals, including humans, have nipples, but a few male species, including mice, do not. It is currently believed that testosterone produced by the fetal testes during sexual differentiation causes nipple atrophy in male mice. However, since all male mammals produce testosterone during sexual differentiation, how nipples are retained in most male mammals, including humans, remains unknown. This study compared mammary gland development and hormonal regulation between guinea pigs and mice and found that androgen receptor (AR) is exclusively present in the developing mammary glands of mice during sexual differentiation. In mice, testosterone binds to AR, activating androgen-responsive genes and inducing apoptosis and autophagy in epithelial cells of the nipple bud, leading to nipple atrophy. During guinea pig embryonic development, the absence of the AR inactivates AR pathway genes and activates Wnt pathway genes, promoting cell proliferation and inhibiting programmed cell death, thereby inducing nipple formation.