Assessing the mammary gland of nonhuman primates: effects of endogenous hormones and exogenous hormonal agents and growth factors

Cline, J. Mark

doi:10.1002/bdrb.20112

Cited by 39 publications

(43 citation statements)

References 97 publications

(130 reference statements)

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“…Rhesus macaques share many aspects of growth, development, and reproduction with humans (Cline 2007; Leigh, 2009; Machado, 2013), but on an accelerated time scale (Valerio et al 1969). As such, early reproductive debut in rhesus macaques corresponds to young adolescent pregnancy <16 years of age in humans (Vogel et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta)

Pittet

Johnson

Hinde

2017

American J Phys Anthropol

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Objectives The age at which females initiate their reproductive career is a critical life-history parameter with potential consequences on their residual reproductive value and lifetime fitness. The age at reproductive debut may be intimately tied to the somatic capacity of the mother to rear her young, but relatively little is known about the influence of age of first birth on milk synthesis within a broader framework of reproductive scheduling, infant outcomes, and other life-history tradeoffs. Material and Methods Our study investigated the predictors of age at first reproduction among 108 captive rhesus macaque (Macaca mulatta) females, and associations with their milk synthesis at peak lactation, infant mass and ability to subsequently conceive and reproduce. Results The majority of females reproduced in their fourth year (typical breeders); far fewer initiated their reproductive career one year earlier or one year later (respectively early and late breeders). Early breeders (3-year-old) benefited from highly favorable early life development (better juvenile growth, high dominance rank) to accelerate reproduction, but were impaired in milk synthesis due to lower somatic resources and their own continued growth. Comparatively, late breeders suffered from poor developmental conditions, only partially compensated by their delayed reproduction, and evinced compromised milk synthesis. Typical breeders not only produced higher available milk energy but also had best reproductive performance during the breeding and birth seasons following primiparity. Discussion Here we refine and extend our understanding of how life-history tradeoffs manifest in the magnitude, sources, and consequences of variation in age of reproductive debut. These findings provide insight into primate reproductive flexibility in light of constraints and opportunities.

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Section: Discussionmentioning

confidence: 99%

Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta)

Pittet

Johnson

Hinde

2017

American J Phys Anthropol

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“…Whole mounts were stained using 0.27% Toluidine Blue as previously described (15, 23). Whole mounts were photographed in toto , and the digital images were used for morphologic measures.…”

Section: Methodsmentioning

confidence: 99%

“…For measurement of mammary gland epithelial area, H&E-stained slides were digitized (Infinity 3 digital camera, Lumenera, Ottawa, Canada; Adobe Photoshop version 6.0, San Jose, CA) and measured with methods described previously (23) and modified as follows for developmental structures. Breast epithelium was subdivided into lobuloalveolar and ductal compartments.…”

Section: Methodsmentioning

confidence: 99%

Dietary Soy Effects on Mammary Gland Development during the Pubertal Transition in Nonhuman Primates

Dewi

Wood

Lees

et al. 2013

Cancer Prevention Research

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While epidemiologic studies suggest that soy intake early in life may reduce breast cancer risk, there are also concerns that exposure to soy isoflavones during childhood may alter pubertal development and hormonal profiles. Here, we assessed the effect of a high-soy diet on pubertal breast development, sex hormones, and growth in a nonhuman primate model. Pubertal female cynomolgus monkeys were randomized to receive a diet modeled on a typical North American diet with one of two protein sources for ~4.5 years: i) casein/lactalbumin (CL, n=12, as control) or ii) soy protein isolate with a human equivalent dose of 120 mg/day isoflavones (SOY, n=17), which is comparable to approximately four servings of soy foods. Pubertal exposure to the SOY diet did not alter onset of menarche, indicators of growth and pubertal progression, or circulating estradiol and progesterone concentrations. Greater endometrial area was seen in the SOY group on the first of 4 postmenarchal ultrasound measurements (P<0.05). There was a subtle effect of diet on breast differentiation whereby the SOY group showed higher numbers of differentiated large-sized lobular units and a lower proportion with immature ducts following menarche (P<0.05). Numbers of small lobules and terminal end buds and mammary epithelial cell proliferation did not differ by diet. Expression of progesterone receptor was lower in immature lobules of soy-fed animals (P<0.05). Our findings suggest that consumption of soy starting before menarche may result in modest effects consistent with a more differentiated breast phenotype in adulthood.

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“…The female human and macaque breast share many histological and physiological features which result in comparable tissue and transcriptional responses to exogenous sex hormones. 25 For these reasons, this model has been used in many prior studies to evaluate the hormone-associated risk profile of menopausal HTs and SERMs. 26–29 Other advantages of this model are the ability to perform repeat breast biopies without sacrifice and assess the effects of new HTs on multiple organ systems in the same subject in an effort to determine a global benefit to risk profile.…”

Section: Methodsmentioning

confidence: 99%

Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys

Ethun

Wood

et al. 2012

Menopause

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Objective Concerns about increased breast cancer risk with estrogen and progestin therapy have led to an increased interest in progestin alternatives. The main objective of this study was to determine if bazedoxifene acetate (BZA), a new selective estrogen receptor modulator (SERM), would antagonize the proliferative and transcriptional effects of conjugated equine estrogens (CEE) in the breast. Methods As part of a 20 month preclinical trial, ninety-five ovariectomized cynomolgus macaques (Macaca fascicularis) were randomized to receive no treatment or treatment with BZA (20 mg/d), CEE (0.45 mg/d), or BZA and CEE in combination (women’s daily equivalent doses). Data presented here include breast effects following 6 months of treatment. Endpoints included histomorphometry, histopathologic evaluations, gene microarray assays, PCR quantification of specific ERα activity markers, and immunohistochemical detection of sex steroid receptors, and the proliferation marker Ki67. Results BZA+CEE and BZA resulted in significantly less total epithelial density, lobular enlargement, and Ki67 immunolabeling in the terminal ducts compared to CEE alone (P < 0.05 for all). The addition of BZA to CEE antagonized the expression of ERα-regulated genes such as GREB1 and TFF1 (P < 0.01 for both), while BZA alone had minimal effects on ERα-mediated transcriptional activity. BZA and BZA+CEE did not significantly up-regulate genes related to cell cycle progression and proliferation. BZA with and without CEE also resulted in less lobular and terminal duct ERα immunolabeling compared to control and CEE (P < 0.0001 for all). Conclusions These findings demonstrate that BZA given at a clinically relevant dose is an estrogen antagonist in the breast, supporting the idea that CEE + BZA may provide a lower breast cancer risk profile compared to traditional estrogen + progestin therapies.

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Assessing the mammary gland of nonhuman primates: effects of endogenous hormones and exogenous hormonal agents and growth factors

Cited by 39 publications

References 97 publications

Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta)

Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta)

Dietary Soy Effects on Mammary Gland Development during the Pubertal Transition in Nonhuman Primates

Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys

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