The in vivo studies presented here demonstrate that epidermal growth factor (EGF) is an important autocrine and/or paracrine mediator of estrogen-induced growth and differentiation in mouse uterus and vagina. An antibody specific for EGF significantly inhibited estrogeninduced uterine and vaginal growth, thereby implicating EGF involvement in estrogen action. Furthermore, EGF administered via slow-release pellets in ovariectomized mice acted as a potent uterine and vaginal mitogen as well as an inducer of vaginal keratinization. Experiments with ovariectomized, adrenalectomized, hypophysectomized mice indicated that EGF mitogenesis does not require pituitary or adrenal hormones. Treatment with EGF also mimicked estrogen in the induction of uterine lactoferrin (a major estrogen-inducible secretory protein) mRNA and protein. These data suggest that EGF has estrogen-like effects in the promotion of cell growth in the reproductive tract and that EGF may serve as an important mediator of estrogen action in vivo.Estrogen-induced growth of various target tissues is mediated, in part, by the production of polypeptide growth factors, which may act in an autocrine or paracrine fashion to stimulate proliferation (1, 2). Two polypeptide growth factors, insulin-like growth factor I and epidermal growth factor (EGF), have been associated with the induction of uterine growth by estrogen (2, 3). Our laboratory and others have demonstrated that immunoreactive EGF precursor is present in the mouse uterus (3, 4), that estrogen treatment enhances the expression of EGF (3, 4) and EGF receptor (5) in the uterus, and that EGF is a potent mitogen in mouse uterine cell cultures (6). These studies provide evidence suggesting that EGF plays an important role in estrogen-induced uterine growth.Previous studies (3, 6) suggesting that EGF plays a role in uterine growth led us to further evaluate the role of EGF as a potential regulator of reproductive-tract growth in vivo. In this study, we demonstrate that estrogen action is inhibited by an EGF-specific antibody and that in vivo exposure to EGF alone mimics estrogen in the induction of uterine and vaginal growth and differentiation. Our results strongly suggest that EGF acts as an estrogen-inducible physiological mediator of mouse reproductive-tract growth in vivo. MATERIALS AND METHODS Quantitation of Uterine and Vaginal Growth FollowingExposure to an EGF-Specific Antibody. To determine whether an antibody specific for EGF could inhibit estrogen-induced growth, slow-release cholesterol-based pellets containing an antibody against EGF (whole antiserum; 2.5 mg per pellet; Collaborative Research) were prepared by Innovative Research of America. These pellets were divided into fourths and one quarter was implanted under the kidney capsule of 8-week-old female CD-1 mice that had been ovariectomized for at least 3 weeks. Appropriate control pellets containing normal whole serum (rabbit; 2.9 mg per pellet; Calbiochem) were also implanted. Three days following pellet implantation, the anim...
Objective To describe fertility patients' preferences for disposition of cryopreserved embryos and determine factors important to these preferences Design Cross-sectional survey conducted between June 2006 and July 2007 Setting Nine geographically diverse U.S. fertility clinics Participants 1020 fertility patients with cryopreserved embryos Interventions Self-administered questionnaire Main Outcome Measures Likelihood of selecting each of five conventional embryo disposition options: store for reproduction, thaw and discard, donate to another couple, freeze indefinitely, and donate for research; likelihood of selecting each of two alternative options identified in previous research: placement of embryos in the woman's body at an infertile time, and a disposal ceremony; importance of each of 26 considerations to disposition decisions; and views on the embryo's moral status. Results 54% of respondents with cryopreserved embryos were very likely to use them for reproduction, 21% were very likely to donate for research, 7% or fewer were very likely to choose any other option. Respondents who ascribed high importance to concerns about the health or well-being of the embryo, fetus, or future child were more likely to thaw and discard embryos or freeze them indefinitely. Conclusions Fertility patients frequently prefer disposition options not available to them or find available options unacceptable. Restructuring and standardizing the informed consent process and ensuring availability of all disposition options may benefit patients, facilitate disposition decisions and address problems of long term storage.
A total of 256 men were studied to evaluate whether serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) impacted semen quality or reproductive hormones. Blood and semen were collected and analyzed for perfluorochemicals and reproductive and thyroid hormones. Semen quality was assessed using standard clinical methods. Linear and logistic modeling was performed with semen profile measurements as outcomes and PFOS and PFOA in semen and plasma as explanatory variables. Adjusting for age, abstinence, and tobacco use, there was no indication that PFOA or PFOS was significantly associated with volume, sperm concentration, percent motility, swim-up motility and concentration, and directional motility (a function of motility and modal progression.) Follicle stimulating hormone was not associated with either PFOA or PFOS. Luteinizing hormone was positively correlated with plasma PFOA and PFOS, but not semen PFOS. Important methodological concerns included the lack of multiple hormonal measurements necessary to address circadian rhythms.
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