Pre-birth acquisition of personhood: Incremental accrual of attributes as the framework for individualization by serial and concurrently acting developmental factors.

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.

Application of the estrogen threshold hypothesis to the physiologic hypoestrogenemia of lactation.

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.

Modeling endocrine control of the pituitary-ovarian axis: androgenic influence and chaotic dynamics.

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.

Inhibition of Neu-induced mammary carcinogenesis in transgenic mice expressing ERΔ3, a dominant negative estrogen receptor α variant.

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.

Accelerated mammary tumor onset in a HER2/Neu mouse model exposed to DDT metabolites locally delivered to the mammary gland.

Background: The association of DDT (dichlorodiphenyltrichloroethane) with breast cancer is controversial, but animal studies directly linking DDT to risk are lacking. Concerns with DDT reside in its environmental persistence, bioaccumulation in breast adipose tissue, and endocrine-disrupting actions. Whereas most attention has been focused on estrogenic congeners, we tested the cancer-inducing potential of the antiandrogen, p,p´-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the most prevalent and persistent DDT metabolite.

Interactions between life stress factors and carrying the APOE4 allele adversely impact self-reported health in old adults.

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.

Changes in serum antimüllerian hormone levels across the ovulatory menstrual cycle in late reproductive age.

Objective: The aim of this study was to assess the pattern of serum antimüllerian hormone (AMH) across the normal ovulatory menstrual cycle in women in late reproductive age when ovarian follicle reserve and, hence, serum AMH levels are reduced.

Methods: Serum AMH levels were determined by enzyme-linked immunosorbent assay across the ovulatory menstrual cycle from women in mid (n = 18) and late (n = 43) reproductive life, including the menopausal transition.

Result: : No intracycle variation in AMH level was observed in women in mid reproductive life nor in 33% (n = 14) of women with normal ovulatory cycles in late reproductive age.

Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications.

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.

Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition.

Objective: The menopausal transition is characterized by irregular menstrual cycles and unpredictable hormone levels, including dramatic swings in estradiol (E2). An increasing number of studies have found variable high E2 and low luteal phase progesterone occur with progression of Stages of Reproductive Aging Workshop (STRAW)stage, but the cause remains unclear. To explore the causes of the erratic changes in E2, individual within-cycle secretion patterns of E2, progesterone, follicle-stimulating hormone, luteinizing hormone, inhibin A, and inhibin B were explored in detail.

Black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbB2.

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.

Interrelationships between ovarian and pituitary hormones in ovulatory menstrual cycles across reproductive age.

Context: Ovarian hormones regulate pituitary gonadotropin secretion across the menstrual cycle via negative and positive feedback mechanisms. The contribution of individual hormones is complex and is a continuing area of research.

Objective: The aim of the study was to identify relationships between LH/FSH and estradiol, progesterone, inhibin A, inhibin B, and anti-Mullerian hormone (AMH) in ovulatory menstrual cycles across reproductive age.

A proposed classification system for menstrual cycles in the menopause transition based on changes in serum hormone profiles.

Objective: To characterize menstrual cycles in women in late reproductive age and the menopause transition, based on changes in serum hormone levels.

Design: Serum levels of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone, inhibin A, inhibin B, and antimüllerian hormone, as previously reported as mean data grouped according to the Stages of Reproductive Aging Workshop proposals, were analyzed in 55 women aged 45 to 55 and compared with those in 21 women aged 21 to 35.

Results: The ovulatory cycles in the older women were divided into three types.

Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system.

Context: Female reproductive aging based on changes in menstrual cycle length and frequency progresses through a number of stages as defined by the Stages of Reproductive Aging Workshop (STRAW) staging criteria.

Objective: This paper provides a comprehensive description of the endocrine features associated with the STRAW stages.

Design: Healthy women aged 21-35 and 45-55 yr submitted three blood samples a week over a single menstrual cycle.

Effect of the isoflavone genistein against galactose-induced cataracts in rats.

Worldwide, ocular cataracts are a major cause of human blindness. A key goal of cataract-related research is to identify simple, cost-efficient but effective ways to prevent cataract formation or progression. Genistein is a naturally occurring dietary isoflavone with well-documented estrogenic, antioxidant, and protein tyrosine kinase inhibitor activity, which in turn modulates the activity of several enzymes involved in cell signaling and proliferation.

Dioxin-like activity and maternal thyroid hormone levels in second trimester maternal serum.

Objective: Developmental exposure to dioxin-like compounds has been associated with cognitive and motor impairments in children. These toxicants have been shown to be thyroid toxicants in animal studies. Therefore, the objective of this study was to quantify the overall dioxin-like activity in maternal serum and determine the association between dioxin-like activity and thyroid hormone levels.

Dietary galactose inhibits GDF-9 mediated follicular development in the rat ovary.

Clinical evidence suggests an association between galactosemia and premature ovarian failure, but the mechanism is still not fully understood. Growth differentiation factor-9 (GDF-9) is thought to be an obligatory growth factor during the gonadotropin-independent phase of folliculogenesis. The objective of this study was to examine the effects of galactose on initiation of folliculogenesis in the peripubertal interval and the connection between galactose toxicity and GDF-9 expression in the ovary.

Ovarian effects of a high lactose diet in the female rat.

Young women with galactosemia experience ovarian failure at a very early age raising concern about the ovarian toxicity of galactose. While galactose may be present in the diet as a monosaccharide, it is predominantly derived from cleavage of the disaccharide lactose within the intestine. Our previous studies in animals have shown that high galactose diets inhibit ovarian follicular development and long-term exposure to high lactose diets retards growth of rats.

Metabolic effects of dietary lactose in adult female rats.

As an outgrowth of our interest in the potential toxicity of dietary galactose, we investigated the metabolic effects of high lactose diets in Long-Evans female rats. Seventy-five Long-Evans female rats (25-day-old) were randomized to receive one of 3 diets for 7 months: glucose diet (CON); low lactose diet (10.5%, LLD); or a high lactose diet (41.

Effects of genistein or soy milk during late gestation and lactation on adult uterine organization in the rat.

In utero and lactational exposure to estrogenic agents has been shown to influence morphological and functional development of reproductive tissues. Thus, consumption of dietary phytoestrogens, such as isoflavones, during pregnancy and lactation could influence important periods of development, when the fetus and neonate are more sensitive to estrogen exposure. In this study, reproductive outcomes after developmental exposure to isoflavones were examined in Long-Evans rats maternally exposed to isoflavones via a commercial soy beverage or as the isolated isoflavone, genistein.

Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein.

In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1x the acceptable daily intake.

Dietary compounds in relation to dietary diversity and human health.

The human diet contains numerous endocrine-active compounds that influence mammalian physiology. The effects of these dietary compounds may be mediated by interaction with well-characterized intracellular hormone receptors or by other effects on patterns of endogenous hormone production, metabolism, target tissue signaling, growth, or differentiation. Because humans evolved as omnivores, the spectrum of dietary compounds that can be tolerated at modest levels of intake without frank toxicity is broad.

Human developmental exposure to endocrine active compounds.

Quantification of exposure to environmental contaminants such as endocrine active chemicals (EACs) during critical periods of development, particularly in utero, remains largely unexplored. Therefore, we tested the hypothesis that EACs can be detected and quantified in second trimester human amniotic fluid. Amniotic fluid was obtained from women (n=175) undergoing routine amniocentesis between 14 and 21 weeks gestation.