Browsing by Author "Hughes, Claude L"

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    Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications.
    (Critical reviews in toxicology, 2010-08) Sadeu, JC; Hughes, Claude L; Agarwal, Sanjay; Foster, Warren G
    Reproductive function and fertility are thought to be compromised by behaviors such as cigarette smoking, substance abuse, and alcohol consumption; however, the strength of these associations are uncertain. Furthermore, the reproductive system is thought to be under attack from exposure to environmental contaminants, particularly those chemicals shown to affect endocrine homeostasis. The relationship between exposure to environmental contaminants and adverse effects on human reproductive health are frequently debated in the scientific literature and these controversies have spread into the lay press drawing increased public and regulatory attention. Therefore, the objective of the present review was to critically evaluate the literature concerning the relationship between lifestyle exposures and adverse effects on fertility as well as examining the evidence for a role of environmental contaminants in the purported decline of semen quality and the pathophysiology of subfertility, polycystic ovarian syndrome, and endometriosis. The authors conclude that whereas cigarette smoking is strongly associated with adverse reproductive outcomes, high-level exposures to other lifestyle factors are only weakly linked with negative fertility impacts. Finally, there is no compelling evidence that environmental contaminants, at concentrations representative of the levels measured in contemporary biomonitoring studies, have any effect, positive or negative, on reproductive health in the general population. Further research using prospective study designs with robust sample sizes are needed to evaluate testable hypotheses that address the relationship between exposure and adverse reproductive health effects.
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    Application of the estrogen threshold hypothesis to the physiologic hypoestrogenemia of lactation.
    (Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, 2015-03) Agarwal, Sanjay K; Kim, Julie; Korst, Lisa M; Hughes, Claude L
    OBJECTIVE: This study determined the impact of breastfeeding on hypoestrogenic symptoms among women in the postpartum period and correlated these findings with the Estrogen Threshold Hypothesis, which postulates that the hypoestrogenic symptoms experienced are related to circulating estrogen levels. STUDY DESIGN: Using a survey instrument that combined previously validated assessments of postpartum mood changes and menopausal symptoms, women were evaluated in the immediate postpartum period, prior to hospital discharge, and at 3 and 6 weeks postpartum. Each time period was analyzed independently, in a cross-sectional design, where women were categorized as "breastfeeding" or "bottle feeding." RESULTS: Of 236 women recruited, 171 (72.5%) intended to breastfeed, and 62 (26.3%) intended to bottle feed. At both the 3- and 6-week postpartum evaluations, a similar percentage of women in the breastfeeding and bottle-feeding groups reported hot flashes. However, breastfeeding women were more likely to report vaginal dryness than those who did not breastfeed: 20/150 (13.3%) versus 3/80 (3.8%) at 3 weeks, p<0.05; 25/143 (17.5%) versus 2/87 (2.3%) at 6 weeks, p<0.001. CONCLUSIONS: The Estrogen Threshold Hypothesis accurately predicts the findings of increased reported vaginal dryness but not hot flashes during lactation.
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    Black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbB2.
    (Cancer research, 2008-10) Davis, Vicki L; Jayo, Manuel J; Ho, Arline; Kotlarczyk, Mary P; Hardy, Mary L; Foster, Warren G; Hughes, Claude L
    Black cohosh is an herbal extract that is often used as an alternative to estrogen-based replacement therapies to treat hot flushes that frequently accompany the transition to menopause. Although cancer-free women as well as breast cancer patients and survivors use black cohosh to relieve vasomotor symptoms, there is limited information on its potential to influence breast cancer development or progression. Therefore, in this study, the effects of black cohosh on mammary tumorigenesis were investigated in the MMTV-neu mouse model due to its similarities to HER2(+) breast cancer, including stochastic development of mammary tumors, which frequently progress to metastatic disease. Using an adjusted dose for the mice to correlate to the recommended dose in women (40 mg/d), no differences were detected in the incidence or onset of mammary tumors in black cohosh-treated versus control females. The lack of effect on mammary tumor development suggests that black cohosh would not influence breast cancer risk if given to women before tumor formation. In contrast, black cohosh significantly increased the incidence of lung metastases in tumor-bearing animals compared with mice fed the isoflavone-free control diet. Additional studies will be needed to correlate these findings to women taking different black cohosh products at various times during breast cancer development; however, these results suggest caution for women using black cohosh, especially for extended periods of time. As metastatic progression is linked to patient survival, these data stress the importance of investigating how women's therapies influence all stages of mammary tumorigenesis, particularly for assessing their safety.
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    Gene expression in oogenesis and implications for transgenerational effects of environmental toxicants.
    (Biology of reproduction, 2011-01) Foster, Warren G; Hughes, Claude L
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    Inhibition of Neu-induced mammary carcinogenesis in transgenic mice expressing ERΔ3, a dominant negative estrogen receptor α variant.
    (Hormones & cancer, 2012-12) Davis, Vicki L; Shaikh, Firdos; Gallagher, Katie M; Villegas, Michael; Rea, Sheri L; Cline, J Mark; Hughes, Claude L
    The estrogen receptor α (ERα) splicing variant with an in-frame deletion of exon 3 (ERΔ3) is frequently expressed in the normal breast, but its influence on tumorigenesis has not been explored. In vitro, ERΔ3 has dominant negative activity, suggesting it may suppress estrogen stimulation in the breast. ERΔ3 may inhibit classical signaling on estrogen response element (ERE)-regulated genes as well as activate non-classical pathways at Sp1 and AP-1 sites. Transgenic mice were developed that express mouse ERΔ3 in all tissues examined, including the mammary gland. To investigate if ERΔ3 expression affects tumorigenesis, ERΔ3 mice were crossbred with MMTV-Neu mice. Mammary tumor onset was significantly delayed in ERΔ3/Neu versus MMTV-Neu females and metastatic incidence and burden was significantly reduced. Consequently, ERΔ3 expression suppressed tumor development and metastasis in this aggressive model of HER2/Neu-positive breast cancer. To determine if ER ligands with anticancer activity may augment ERΔ3 protection, the bitransgenic mice were treated with tamoxifen and soy isoflavones starting at age 2 months. Soy protein with isoflavones (181 mg/1,800 kcal) did not affect tumor development in MMTV-Neu or ERΔ3/Neu mice; however, metastatic progression was not inhibited in soy-treated ERΔ3/Neu mice, as it was in untreated ERΔ3/Neu mice. In contrast, tamoxifen (20 mg/1,800 kcal) significantly enhanced tumor prevention in ERΔ3/Neu versus MMTV-Neu mice (98% vs. 81% tumor free). The results in ERΔ3/Neu mice demonstrate that ERΔ3 influences estrogen-dependent mammary carcinogenesis and, thus, may be protective in women expressing ERΔ3 in the breast. However, exposure to different estrogens may augment or block its beneficial effects.
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    Interactions between life stress factors and carrying the APOE4 allele adversely impact self-reported health in old adults.
    (The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2011-10) Zeng, Yi; Hughes, Claude L; Lewis, Megan A; Li, Jianxin; Zhang, Fengyu
    Based on the multiple logistic regression analysis of data from a random sample of 1,023 old adults collected in Taiwan in 2000, we found that interactions between carrying the APOE4 allele and one of four life stress factors (relocated mainlander, living in a crowded household with six or more persons, living in an earthquake-damaged house, and monthly financial difficulty) significantly increased the odds ratio of poor self-reported health. Correlations between carrying the APOE4 allele and the life stress factors were ruled out by statistical tests. These life stress factors had a substantially larger adverse impact on self-reported health in APOE4 allele carriers than in noncarriers. This study provides evidence that interaction between carrying APOE4 allele and chronic life stressors has significant impacts on self-reported health while controlling for various sociodemographic and health behavior factors. Further studies with richer biomarkers are warranted for deeper understanding of the biological mechanisms.
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    Modeling endocrine control of the pituitary-ovarian axis: androgenic influence and chaotic dynamics.
    (Bulletin of mathematical biology, 2014-01) Hendrix, Angelean O; Hughes, Claude L; Selgrade, James F
    Mathematical models of the hypothalamus-pituitary-ovarian axis in women were first developed by Schlosser and Selgrade in 1999, with subsequent models of Harris-Clark et al. (Bull. Math. Biol. 65(1):157-173, 2003) and Pasteur and Selgrade (Understanding the dynamics of biological systems: lessons learned from integrative systems biology, Springer, London, pp. 38-58, 2011). These models produce periodic in-silico representation of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P4), inhibin A (InhA), and inhibin B (InhB). Polycystic ovarian syndrome (PCOS), a leading cause of cycle irregularities, is seen as primarily a hyper-androgenic disorder. Therefore, including androgens into the model is necessary to produce simulations relevant to women with PCOS. Because testosterone (T) is the dominant female androgen, we focus our efforts on modeling pituitary feedback and inter-ovarian follicular growth properties as functions of circulating total T levels. Optimized parameters simultaneously simulate LH, FSH, E2, P4, InhA, and InhB levels of Welt et al. (J. Clin. Endocrinol. Metab. 84(1):105-111, 1999) and total T levels of Sinha-Hikim et al. (J. Clin. Endocrinol. Metab. 83(4):1312-1318, 1998). The resulting model is a system of 16 ordinary differential equations, with at least one stable periodic solution. Maciel et al. (J. Clin. Endocrinol. Metab. 89(11):5321-5327, 2004) hypothesized that retarded early follicle growth resulting in "stockpiling" of preantral follicles contributes to PCOS etiology. We present our investigations of this hypothesis and show that varying a follicular growth parameter produces preantral stockpiling and a period-doubling cascade resulting in apparent chaotic menstrual cycle behavior. The new model may allow investigators to study possible interventions returning acyclic patients to regular cycles and guide developments of individualized treatments for PCOS patients.
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    Pre-birth acquisition of personhood: Incremental accrual of attributes as the framework for individualization by serial and concurrently acting developmental factors.
    (Frontiers in reproductive health, 2023-01) Hughes, Claude L; Hughes, Gavin C
    Discrete events and processes influence development of individual humans. Attribution of personhood to any individual human being cannot be disconnected from the underlying biological events and processes of early human development. Nonetheless, the philosophical, sociological and legal components that are integral to the meaning of the term as commonly used cannot be deduced from biology alone. The challenge for biomedical scientists to inform discussion in this arena then rests on profiling the key biological events and processes that must be assessed when considering how one might objectively reason about the task of superimposing the concept of personhood onto the developing biological entity of a potential human being. Endogenous genetic and epigenetic events and exogenous developmental milieu processes diversify developmental trajectories of potential individual humans prior to livebirth. First, fertilization and epigenetic resetting of each individual's organismic clock to time zero (t = 0) at the gastrulation/primitive streak stage (day 15 of embryogenesis), are two discrete unseen biological events that impact a potential individual human's attributes. Second, those two discrete unseen biological events are immersed in the continuous developmental process spanning pre-fertilization and gestation, further driving individualization of diverse attributes of each future human before the third discrete and blatant biological event of parturition and livebirth. Exposures of the gravida to multiple diverse exogenous exposures means that morphogenesis and physiogenesis of every embryo/fetus has individualized attributes for its future human lifespan. Our proposed framework based on the biological discrete events and processes spanning pre-fertilization and prenatal development, implies that personhood should be incrementally attributed, and societal protections should be graduated and applied progressively across the pre-birth timespan.
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    The Impact of Endometriosis on the Health of Women.
    (BioMed research international, 2015-01) Hughes, Claude L; Foster, Warren G; Agarwal, Sanjay K; Mettler, Liselotte