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Vasantha Padmanabhan - One of the best experts on this subject based on the ideXlab platform.
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Developmental Programming: Gestational Bisphenol-A Treatment Alters Trajectory of Fetal Ovarian Gene Expression
Endocrinology, 2013Co-Authors: Almudena Veiga-lopez, Lacey J. Luense, Lane K. Christenson, Vasantha PadmanabhanAbstract:Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, Hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (>1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.
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Developmental Programming: Excess Weight Gain Amplifies the Effects of Prenatal Testosterone Excess On Reproductive Cyclicity—Implication for Polycystic Ovary Syndrome
Endocrinology, 2008Co-Authors: Teresa L. Steckler, Carol Herkimer, Daniel A. Dumesic, Vasantha PadmanabhanAbstract:Sheep exposed to testosterone (T) during early to midgestation exhibit reproductive defects that include Hypergonadotropism, functional hyperandrogenism, polycystic ovaries, and anovulatory infertility, perturbations similar to those observed in women with polycystic ovary syndrome. Obesity increases the severity of the phenotype in women with polycystic ovary syndrome. To determine whether prepubertal weight gain would exaggerate the reproductive disruptions in prenatal T-treated sheep, pregnant sheep were injected with 100 mg T propionate (∼1.2 mg/kg) im twice weekly, from d 30–90 of gestation. Beginning about 14 wk after birth, a subset of control and prenatal T-treated females were overfed to increase body weight to 25% above that of controls. Twice-weekly progesterone measurements found no differences in timing of puberty, but overfed prenatal T-treated females stopped cycling earlier. Detailed characterization of periovulatory hormonal dynamics after estrous synchronization with prostaglandin F2α fo...
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developmental programming differential effects of prenatal exposure to bisphenol a or methoxychlor on reproductive function
Endocrinology, 2006Co-Authors: Mozhgan Savabieasfahani, Kurunthachalam Kannan, Olga Astapova, Neil P Evans, Vasantha PadmanabhanAbstract:Increased occurrence of reproductive disorders has raised concerns regarding the impact of endocrine-disrupting chemicals on reproductive health, especially when such exposure occurs during fetal life. Prenatal testosterone (T) treatment leads to growth retardation, postnatal Hypergonadotropism, compromised estradiol-positive feedback, polycystic ovaries, and infertility in the adult. Prenatal dihydrotestosterone treatment failed to affect ovarian morphology or estradiol-positive feedback, suggesting that effects of prenatal T may be facilitated via conversion of T to estradiol, thus raising concerns regarding fetal exposure to estrogenic endocrine-disrupting chemicals. This study tested whether fetal exposure to methoxychlor (MXC) or bisphenol A (BPA) would disrupt cyclicity in the ewe. Suffolk ewes were administered MXC (n = 10), BPA (n = 10) (5 mg/kg·d sc in cotton seed oil) or the vehicle (C; n = 16) from d 30 to 90 of gestation. On d 60 of treatment, maternal MXC concentrations in fat tissue and BPA ...
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Fetal Programming: Excess Prenatal Testosterone Reduces Postnatal Luteinizing Hormone, But Not Follicle-Stimulating Hormone Responsiveness, to Estradiol Negative Feedback in the Female
Endocrinology, 2005Co-Authors: Hirendra N. Sarma, Mohan Manikkam, Carol Herkimer, James M. Dell’orco, Kathleen B. Welch, Douglas L. Foster, Vasantha PadmanabhanAbstract:Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal Hypergonadotropism manifest as a selective increase in LH. This Hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30–90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 μg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during an...
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Fetal Programming: Prenatal Testosterone Treatment Causes Intrauterine Growth Retardation, Reduces Ovarian Reserve and Increases Ovarian Follicular Recruitment
Endocrinology, 2005Co-Authors: Teresa L. Steckler, Jinrong Wang, Frank F. Bartol, Shyamal K. Roy, Vasantha PadmanabhanAbstract:Exposure to testosterone (T) during d 30-90 of fetal life results in low-birth-weight offspring, Hypergonadotropism, multifollicular ovaries, and early cessation of cyclicity. The multifollicular phenotype may result from failure of follicles to regress and consequent follicular persistence or, alternatively, increased follicular recruitment. We tested the hypothesis that prenatal exposure to excess T causes intrauterine growth retardation and increases ovarian follicular recruitment. Time-mated pregnant ewes were treated with 100 mg T propionate in cottonseed oil or vehicle twice weekly from d 30-90 of gestation. Ewes were euthanized near term, from d 139-141 of gestation (term is 147 d). After determining fetal measures and organ weights, ovaries were removed from fetuses of control and T-treated dams, and follicular distribution in each ovary was determined by morphometric quantification. Total number and percentage distribution of the various classes of follicles (primordial, primary, preantral, and antral follicles) were compared between treatment groups. Prenatally T-treated female fetuses were smaller in size, had an increased head circumference to fetal weight ratio (P < 0.01), increased adrenal to fetal weight ratio (P < 0.05), decreased number of follicles (P < 0.05), a decrease in percentage of primordial follicles (P < 0.001), and a corresponding increase in the remaining classes of follicles (P < 0.05). Ovarian findings support decreased ovarian reserve and enhanced follicular recruitment, potential contributors of early reproductive failure. The extent to which metabolic changes associated with intrauterine growth retardation contribute toward altered trajectory of ovarian folliculogenesis remains to be determined.
Carol Herkimer - One of the best experts on this subject based on the ideXlab platform.
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Developmental Programming: Excess Weight Gain Amplifies the Effects of Prenatal Testosterone Excess On Reproductive Cyclicity—Implication for Polycystic Ovary Syndrome
Endocrinology, 2008Co-Authors: Teresa L. Steckler, Carol Herkimer, Daniel A. Dumesic, Vasantha PadmanabhanAbstract:Sheep exposed to testosterone (T) during early to midgestation exhibit reproductive defects that include Hypergonadotropism, functional hyperandrogenism, polycystic ovaries, and anovulatory infertility, perturbations similar to those observed in women with polycystic ovary syndrome. Obesity increases the severity of the phenotype in women with polycystic ovary syndrome. To determine whether prepubertal weight gain would exaggerate the reproductive disruptions in prenatal T-treated sheep, pregnant sheep were injected with 100 mg T propionate (∼1.2 mg/kg) im twice weekly, from d 30–90 of gestation. Beginning about 14 wk after birth, a subset of control and prenatal T-treated females were overfed to increase body weight to 25% above that of controls. Twice-weekly progesterone measurements found no differences in timing of puberty, but overfed prenatal T-treated females stopped cycling earlier. Detailed characterization of periovulatory hormonal dynamics after estrous synchronization with prostaglandin F2α fo...
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Fetal Programming: Excess Prenatal Testosterone Reduces Postnatal Luteinizing Hormone, But Not Follicle-Stimulating Hormone Responsiveness, to Estradiol Negative Feedback in the Female
Endocrinology, 2005Co-Authors: Hirendra N. Sarma, Mohan Manikkam, Carol Herkimer, James M. Dell’orco, Kathleen B. Welch, Douglas L. Foster, Vasantha PadmanabhanAbstract:Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal Hypergonadotropism manifest as a selective increase in LH. This Hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30–90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 μg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during an...
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Fetal Programming: Testosterone Exposure of the Female Sheep During Midgestation Disrupts the Dynamics of Its Adult Gonadotropin Secretion During the Periovulatory Period
Biology of reproduction, 2004Co-Authors: Mozhgan Savabieasfahani, Carol Herkimer, Douglas L. Foster, James S. Lee, Tejinder Pal Sharma, Vasantha PadmanabhanAbstract:Abstract Prenatal exposure of the female sheep to excess testosterone (T) leads to Hypergonadotropism, multifollicular ovaries, and progressive loss of reproductive cycles. We have determined that prenatal T treatment delays the latency of the estradiol (E2)-induced LH surge. To extend this finding into a natural physiological context, the present study was conducted to determine if the malprogrammed surge mechanism alters the reproductive cycle. Specifically, we wished to determine if prenatal T treatment 1) delays the onset of the preovulatory gonadotropin surge during the natural follicular phase rise in E2, 2) alters pulsatile LH secretion and the dynamics of the secondary FSH surge, and 3) compromises the ensuing luteal function. Females prenatally T-treated from Day 60 to Day 90 of gestation (147 days is term) and control females were studied when they were ∼2.5 yr of age. Reproductive cycles of control and prenatally T-treated females were synchronized with PGF2α, and peripheral blood samples were ...
Teresa L. Steckler - One of the best experts on this subject based on the ideXlab platform.
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Developmental Programming: Excess Weight Gain Amplifies the Effects of Prenatal Testosterone Excess On Reproductive Cyclicity—Implication for Polycystic Ovary Syndrome
Endocrinology, 2008Co-Authors: Teresa L. Steckler, Carol Herkimer, Daniel A. Dumesic, Vasantha PadmanabhanAbstract:Sheep exposed to testosterone (T) during early to midgestation exhibit reproductive defects that include Hypergonadotropism, functional hyperandrogenism, polycystic ovaries, and anovulatory infertility, perturbations similar to those observed in women with polycystic ovary syndrome. Obesity increases the severity of the phenotype in women with polycystic ovary syndrome. To determine whether prepubertal weight gain would exaggerate the reproductive disruptions in prenatal T-treated sheep, pregnant sheep were injected with 100 mg T propionate (∼1.2 mg/kg) im twice weekly, from d 30–90 of gestation. Beginning about 14 wk after birth, a subset of control and prenatal T-treated females were overfed to increase body weight to 25% above that of controls. Twice-weekly progesterone measurements found no differences in timing of puberty, but overfed prenatal T-treated females stopped cycling earlier. Detailed characterization of periovulatory hormonal dynamics after estrous synchronization with prostaglandin F2α fo...
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Fetal Programming: Prenatal Testosterone Treatment Causes Intrauterine Growth Retardation, Reduces Ovarian Reserve and Increases Ovarian Follicular Recruitment
Endocrinology, 2005Co-Authors: Teresa L. Steckler, Jinrong Wang, Frank F. Bartol, Shyamal K. Roy, Vasantha PadmanabhanAbstract:Exposure to testosterone (T) during d 30-90 of fetal life results in low-birth-weight offspring, Hypergonadotropism, multifollicular ovaries, and early cessation of cyclicity. The multifollicular phenotype may result from failure of follicles to regress and consequent follicular persistence or, alternatively, increased follicular recruitment. We tested the hypothesis that prenatal exposure to excess T causes intrauterine growth retardation and increases ovarian follicular recruitment. Time-mated pregnant ewes were treated with 100 mg T propionate in cottonseed oil or vehicle twice weekly from d 30-90 of gestation. Ewes were euthanized near term, from d 139-141 of gestation (term is 147 d). After determining fetal measures and organ weights, ovaries were removed from fetuses of control and T-treated dams, and follicular distribution in each ovary was determined by morphometric quantification. Total number and percentage distribution of the various classes of follicles (primordial, primary, preantral, and antral follicles) were compared between treatment groups. Prenatally T-treated female fetuses were smaller in size, had an increased head circumference to fetal weight ratio (P < 0.01), increased adrenal to fetal weight ratio (P < 0.05), decreased number of follicles (P < 0.05), a decrease in percentage of primordial follicles (P < 0.001), and a corresponding increase in the remaining classes of follicles (P < 0.05). Ovarian findings support decreased ovarian reserve and enhanced follicular recruitment, potential contributors of early reproductive failure. The extent to which metabolic changes associated with intrauterine growth retardation contribute toward altered trajectory of ovarian folliculogenesis remains to be determined.
Oguz Ekmekcioglu - One of the best experts on this subject based on the ideXlab platform.
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Three cases of Klinefelter's syndrome with unilateral absence of vas deferens
Andrologia, 2017Co-Authors: Emre Can Akinsal, Numan Baydilli, Hakan İmamoğlu, Oguz EkmekciogluAbstract:Genital abnormalities such as congenital uni/bilateral absence of the vas deferens are very rare in Klinefelter's syndrome. Here, we report three cases of Klinefelter's syndrome with unilateral absence of the vas deferens. All cases had small testicles, and unilateral vas deferentia were not palpable. Hormonal evaluations revealed Hypergonadotropism. One case had elevated prolactin level, and pituitary adenoma was detected by magnetic resonance imaging. All cases were diagnosed as Klinefelter's syndrome (one of them had mosaicism) cytogenetically, and some CFTR gene mutations were detected. To our knowledge, this is the first case series of both conditions existing simultaneously.
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Klinefelter's syndrome with unilateral absence of vas deferens.
Fertility and Sterility, 2010Co-Authors: Numan Baydilli, Ahmet Gökçe, Sevda Yesim Karabulut, Oguz EkmekciogluAbstract:Objective To report a case of Klinefelter's syndrome with unilateral absence of vas deferens. Design Case report. Setting Tertiary-care infertility clinic. Patient(s) A 28-year-old man with the complaint of infertility. Intervention(s) None. Main Outcome Measure(s) Physical examination, genetic and hormonal evaluation. Result(s) Both testicles were approximately 2 mm, and unilateral vas deferens was not palpable. Hormonal evaluation revealed Hypergonadotropism, and genetic studies revealed a 47,XXY karyotype and delta F508 mutation of the cystic fibrosis gene. Conclusion(s) To our knowledge there are no previous reports of both conditions (Klinefelter's syndrome and unilateral absence of vas deferens) existing simultaneously. A detailed physical examination seems mandatory for patients seeking treatment for infertility, to determine any possible deleterious health-related condition(s) for both themselves and offspring.
Numan Baydilli - One of the best experts on this subject based on the ideXlab platform.
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Three cases of Klinefelter's syndrome with unilateral absence of vas deferens
Andrologia, 2017Co-Authors: Emre Can Akinsal, Numan Baydilli, Hakan İmamoğlu, Oguz EkmekciogluAbstract:Genital abnormalities such as congenital uni/bilateral absence of the vas deferens are very rare in Klinefelter's syndrome. Here, we report three cases of Klinefelter's syndrome with unilateral absence of the vas deferens. All cases had small testicles, and unilateral vas deferentia were not palpable. Hormonal evaluations revealed Hypergonadotropism. One case had elevated prolactin level, and pituitary adenoma was detected by magnetic resonance imaging. All cases were diagnosed as Klinefelter's syndrome (one of them had mosaicism) cytogenetically, and some CFTR gene mutations were detected. To our knowledge, this is the first case series of both conditions existing simultaneously.
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Klinefelter's syndrome with unilateral absence of vas deferens.
Fertility and Sterility, 2010Co-Authors: Numan Baydilli, Ahmet Gökçe, Sevda Yesim Karabulut, Oguz EkmekciogluAbstract:Objective To report a case of Klinefelter's syndrome with unilateral absence of vas deferens. Design Case report. Setting Tertiary-care infertility clinic. Patient(s) A 28-year-old man with the complaint of infertility. Intervention(s) None. Main Outcome Measure(s) Physical examination, genetic and hormonal evaluation. Result(s) Both testicles were approximately 2 mm, and unilateral vas deferens was not palpable. Hormonal evaluation revealed Hypergonadotropism, and genetic studies revealed a 47,XXY karyotype and delta F508 mutation of the cystic fibrosis gene. Conclusion(s) To our knowledge there are no previous reports of both conditions (Klinefelter's syndrome and unilateral absence of vas deferens) existing simultaneously. A detailed physical examination seems mandatory for patients seeking treatment for infertility, to determine any possible deleterious health-related condition(s) for both themselves and offspring.