Perinatal environmental exposures affect mammary development, function, and cancer risk in adulthood

Abstract

Puberty is an important transition that enables reproduction of mammalian species. Precocious puberty, specifically early thelarche (the appearance of breast "buds"), in girls of multiple ethnic backgrounds is a major health problem in the United States and other countries. The cause for a continued decrease in the age of breast development in girls is unknown, but environmental factors likely play a major role. Laboratory and epidemiological studies have identified several individual environmental factors that affect breast development, but further progress is needed. Current research needs include increased attention to and recording of prenatal and neonatal environmental exposures, testing of marketed chemicals for effects on the mammary gland, and understanding of the mammary gland-specific mechanisms that are altered by chemicals. Such research is required to halt the increasing trend toward puberty at earlier ages.

Figure 1

Hormonal control of female puberty. Pubertal timing in humans is controlled by both the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. Breast development (thelarche) and pubic and auxiliary hair development (adrenarche) are regulated by these hormonal circuits. Other abbreviations: ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.

Figure 2

The multiple influences on mammary development. Environmental exposures and endogenous signals may affect endocrine organs as well as tissues near the mammary gland (i.e., fat), and those nearby tissues can send altered messages through the vascular system, culminating in perturbed mammary development. Mammary tissue may also be a direct target of environmental exposures; epithelia, fibroblasts, fat cells, and inflammatory cells express unique and shared receptors that are targets for environmental chemicals. The tight cellular junctions signal across cell types, affecting neighboring cells as well as the target cells. These various endocrine/paracrine/ autocrine signaling mechanisms may affect the status of mammary epithelia over the lifetime of the individual.