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.

Ultrasensitive estrogen levels at 7 years of age predict earlier thelarche: evidence from girls of the growth and obesity Chilean cohort

“…A Pereira and others Ultrasensitive estrogen at 7 years old and early thelarche breast enlargement (35,36). Unfortunately, we did not have EDCs data to confirm this hypothesis.…”

Evaluating chemical effects on mammary gland development: A critical need in disease prevention

“…This definition has been simplified by Zoeller et al [72] to define an ED as "an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action". Compounds that have estrogen-like activity have been studied the most, yet chemicals with anti-estrogenic, androgenic, anti-androgenic, progesteronelike, and thyroid-like activity are also EDs [73].…”

“…This is particularly concerning in light of the current shift toward earlier onset breast development in American and European girls, with girls now beginning breast development (thelarche) earlier and taking longer to reach full breast development than in previous generations [90]. Endogenous hormones play a central role in the onset and regulation of puberty; estrogen, the primary hormone in early breast development, promotes growth of the ducts, while progesterone promotes lobuloalveolar development [73,91]. The physical changes seen in premature thelarche may reflect the onset of pubertal maturation, or they may reflect exposure to endogenous or exogenous hormones independent of the maturity stage of reproductive or adrenal systems (pseudo-puberty) [92].…”

“…Additionally, there are large gaps in our understanding of how MG development is regulated. It is important to understand what specific regulatory factors and genes are involved, as well as which receptor populations are present, and when, in order to understand the mechanisms through which these processes can be disrupted [55,73]. Elucidating the mechanisms involved in breast development would improve our understanding of breast cancer etiology, as well as non-cancer effects, such lactation impairment and gynecomastia.…”

A fejlődési rendellenesség fogalmának átértelmezése: a hibás perinatalis imprinting jelentősége

“…A hibás imprinting, ha a neuroendokrin rendszerben következik be, tehát nemcsak lokálisan okozhat problémát, hanem olyan általános zavarokhoz vezethet, mint az ellenálló képesség csökkené-se, ennek következtében metabolikus betegségek és daganatok kialakulása. Nem véletlen, hogy ezen betegségek okaként egyre inkább előtérbe kerül a perinatalis hiba, amely tartósan rejtve marad és más faktorokkal együtt-működve csak valamikor a felnőttkorban manifesztáló-dik, akár obesitasban, akár daganat vagy egyéb, például pszichiátriai kórkép formájában [42,43,44,45,46,47,48]. Ezen az alapon mind több kórkép kerülhet a fejlő-dési rendellenesség kategóriába.…”