In Utero Exposure to trans-10, cis-12 Conjugated Linoleic Acid Modifies Postnatal Development of the Mammary Gland and its Hormone Responsiveness

Grace E Berryhill,Russell C Hovey,Josephine F Trott,Jana Kraft,Julia M Gloviczki,Adam L Lock

doi:10.1007/s10911-021-09499-y

Grace E Berryhill, Russell C Hovey + Show 4 more

Open Access

https://doi.org/10.1007/s10911-021-09499-y

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Abstract

We previously showed that dietary trans-10, cis-12 conjugated linoleic acid (10,12 CLA) stimulates estrogen-independent mammary growth in young ovariectomized mice. Here we investigated the effects of in utero or postnatal exposure to cis-9, trans-11 (9,11 CLA) and 10,12 CLA on postnatal development of the mammary gland and its responsiveness to ovarian steroids. In the first experiment we fed dams different CLA prior to and during gestation, then cross fostered female pups onto control fed dams prior to assessing the histomorphology of their mammary glands. Pregnant dams in the second experiment were similarly exposed to CLA, after which their female pups were ovariectomized then treated with 17β-estradiol (E), progesterone (P) or E + P for 5 days. In a third experiment, mature female mice were fed different CLA for 28 days prior to ovariectomy, then treated with E, P or E + P. Our data indicate that 10,12 CLA modifies the responsiveness of the mammary glands to E or E + P when exposure occurs either in utero, or postnatally. These findings underline the sensitivity of the mammary glands to dietary fatty acids and reinforce the potential for maternal nutrition to impact postnatal development of the mammary glands and their risk for developing cancer.

Highlights

The in utero environment impacts postnatal development, organ function, and susceptibility to disease [1, 2] and can influence aspects of adult health and wellness including metabolic disorders [3], cardiovascular disease [4], and psychiatric illness [5]
Dietary fats can modify responsiveness of the mammary glands to E, where a high-fat diet (HFD) increased ESR expression in the mammary epithelium of adult mice, whereas ESR expression was decreased in the mammary glands of females born to dams fed a HFD during gestation [12]
We examined the effects of Conjugated linoleic acids (CLA) exposure in utero on hormone responsiveness of the mammary glands postnatally

Summary

Introduction

The in utero environment impacts postnatal development, organ function, and susceptibility to disease [1, 2] and can influence aspects of adult health and wellness including metabolic disorders [3], cardiovascular disease [4], and psychiatric illness [5]. Cross-talk between the epithelial anlagen and the subtending mesenchyme influences formation of the primitive ductal sprout that lies embedded in a well-developed fat pad by the end of gestation [9]. Dietary fats can affect normal development of the mammary glands, and these responses can increase susceptibility of the mammary epithelium to carcinogenesis. Female offspring of rats fed a high-fat diet (HFD) during pregnancy had more TEB during puberty [8], which increased their postnatal susceptibility to mammary tumorigenesis [11]. Dietary fats can modify responsiveness of the mammary glands to E, where a HFD increased ESR expression in the mammary epithelium of adult mice, whereas ESR expression was decreased in the mammary glands of females born to dams fed a HFD during gestation [12]

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