It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by ...pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent acceleration of follicular growth and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, although this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary and an important regulator of folliculogenesis.
Mailed questionnaires can be a convenient method for collecting data on women's health, although poor response rates are a concern.
As part of a survey of women's health conducted in Maryland in ...2001, a randomized trial was performed to assess the effects of two incentives (US dollars 1.00 or a lottery ticket) as well as precontact with an introductory postcard on response rates. Questionnaires were mailed to 3000 women aged 40-60 who were randomized to one of six incentive/precontact groups: lottery/postcard, money/postcard, postcard only, lottery only, money only, or no incentive/no postcard.
The overall response rate was 37.6%. Each incentive/precontact group yielded a higher response rate than the no incentive/no postcard group, although only the response rates for the lottery/postcard group (41.3%) and the money only group (40.0%) were significantly higher than that of the no incentive/no postcard group (33.1%). Money was the only factor that had a significant independent effect on likelihood of response (hazards ratio HR compared to no incentive = 1.22, 95% confidence interval CI = 1.03, 1.43). Response rates were lower in minority ZIP codes, although the effects of the incentives were generally greater than in the nonminority ZIP codes.
These results indicate that response rates to mailed women's health questionnaires may be improved with modest incentives, particularly cash incentives.
Although tamoxifen (TAM) is the predominant adjuvant therapy for estrogen receptor positive (ER(+)) breast tumors, 50% of breast cancer patients do not respond positively to this therapy, or they ...experience adverse side effects. This variability in TAM responsiveness may be due to differences in TAM metabolism that stem from differences in race, age, and body mass index (BMI). Thus, the purpose of this study was to test the hypothesis that race, age, and BMI are associated with the metabolism of TAM to two primary metabolites, N-desmethyltamoxifen (N-DMT) and 4-hydroxytamoxifen (4-OHT).
The study design was cross-sectional, and data were analyzed using independent sample t tests and multiple linear regression models. Breast cancer patients (n = 99) taking TAM for at least 30 days were recruited from a local hospital clinic. Each participant provided informed consent, completed a questionnaire, and donated a blood sample. The questionnaire was used to ascertain race, age, and BMI. The blood samples were used to measure plasma concentrations of TAM, N-DMT, and 4-OHT.
Plasma concentrations of TAM, N-DMT, and 4-OHT differed among individual patients. Age, but not race and BMI, was positively associated with plasma concentrations of TAM and N-DMT, even after adjustment for potential confounders (p = 0.02 for TAM and p = 0.03 for N-DMT).
This study suggests that aging may alter the metabolism of TAM. As increased levels of TAM and TAM metabolites may provide a possible explanation for why older women taking TAM are at increased risk for adverse side effects, future studies should determine whether age-related differences in the concentrations of TAM and TAM metabolites are associated with differences in TAM toxicity or responsiveness.
Exposure of females to environmental chemicals can disrupt reproductive function by altering the normal functions of the oviducts, uterus, cervix, hypothalamus, anterior pituitary, or ovary. ...Compounds that directly affect the ovary can have a profound impact on fertility. Chemicals which destroy oocytes contained in primordial follicles cause early menopause and permanent infertility because only a finite number of these oocytes is contained within the ovary at birth and cannot be replaced. 4-vinylcyclohexene diepoxide (VCD) is one compound that has been shown to destroy oocytes contained in primordial follicles in rats and mice. The purpose of this dissertation was to determine: (1) the contribution of ovarian metabolism to VCD-induced oocyte depletion, (2) whether age is an important factor in the ability of VCD to disrupt reproduction, (3) the initial follicular and cellular target for destruction of oocytes by VCD, and (4) a possible mechanism by which VCD induces ovotoxicity. Data from this dissertation have shown that ovarian metabolism contributes to VCD-induced ovotoxicity because small pre-antral follicles (those follicles which are susceptible to VCD) were shown to have a reduced capacity to detoxify VCD compared to nontarget tissues such as large pre-antral follicles and hepatocytes. It has also been shown that age may not be an important factor in the ability of VCD to destroy oocytes because VCD destroyed oocytes to an equal extent in adult and immature rats. Age, however, was a factor in the ability of VCD to disrupt cyclicity and uterine function since reduced cyclicity and uterine weights were observed in adult, but not immature rats. Additionally, these studies have shown that the initial follicular target for VCD is the primordial follicle, 7-15 days of daily dosing are required to observe oocyte destruction, and VCD modulates secretion of a factor by granulosa cells that may lead to destruction of oocytes via inhibition of protein synthesis. Collectively, these studies have enhanced our understanding of factors which contribute to destruction of oocytes in small pre-antral follicles. Additionally, these studies have provided information regarding interactions of granulosa cells and oocytes contained in those follicles.
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