Embryo Survival, and Fetal and Placental Growth Following Elevation of Maternal Estradiol Blood Concentrations in the Rat1

Bartholomeusz, R. K.; Bruce, Neville; Lynch, Ann‐Maree

doi:10.1095/biolreprod61.1.46

Cited by 37 publications

(35 citation statements)

References 25 publications

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“…Estrogen and progesterone are both essential for the initiation and maintenance of pregnancy and closely related to placental growth. Estrogen is known as an inhibitor of placental growth and its deficiency may induce placental hypertrophy [2,8]. In this study, we found that ketoconazole treatment evoked increased mitosis of trophoblasts in the labyrinth zone on GD 15 without giving any unfavorable effects on maternal condition or severe damage of trophoblasts in the labyrinth zone, although cystic dilatation of maternal sinusoids was observed.…”

Section: Discussionmentioning

confidence: 50%

“…Therefore, even a subtle alteration or deviation of function in the placenta induced by chemicals may lead to miscarriage and/or fetal death. Whereas, overgrowth of placentas is induced with/without fetal effects under various conditions, such as hormonal incoordination [2,8], unfavorable maternal environment, facilitating compensatory recovery of fetal-growth retardation [3,4,17,18], and others. Placental hypertrophy is also detected in the intact uterus with less than six fetuses in rats [7].…”

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confidence: 99%

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Histopathological Effect of Ketoconazole on Rat Placenta

Furukawa

Hayashi

Usuda

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. In order to investigate the morphological effects of ketoconazole on hypertrophied placentas, we examined the sequential histopathological changes in the placenta from rats exposed to ketoconazole. Ketoconazole was administered orally at 0 and 25 mg/kg/day during gestation days (GDs) 12 to 14, and the placentas were sampled on GDs 15, 17 and 21. All dams showed neither effect on body weight nor any abnormal clinical signs during the experimental period. In the treated group, the placentas appeared more hypertrophic with increases in the weight, diameter and thickness on GD 21. Histopathologically, increased thickness was noted in the labyrinth zone and basal zone on GDs 17 and 21, while on GD 15 the change had been already evident in the former zone. In the labyrinth zone, the mitotic figures of the trophoblasts were significantly elevated on GD 15. A multiple cystic dilatation of maternal sinusoids was observed in some placentas on GDs 15, 17 and 21. In the basal zone, an increase in spongiotrophoblasts and clusters of glycogen cells were detected on GDs 17 and 21. In the decidua basalis, there were no significant changes in either histology or thickness between the control and treated group during GDs 15 to 21. In conclusion, ketoconazole increased the population of composed cells in the labyrinth and basal zone, leading to placental hypertrophy in pregnant rats.

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Section: Discussionmentioning

confidence: 50%

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Histopathological Effect of Ketoconazole on Rat Placenta

Furukawa

Hayashi

Usuda

et al. 2008

The Journal of Veterinary Medical Science

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“…Similarly, embryo quality was not responsible, because embryos were obtained from the same pool of donor mice, culture and transfer conditions were the same, and the embryos were randomly allocated to recipients. It is well established that preimplantation changes in the maternal environment can affect fetal development and implantation rates, such as asynchrony between the endometrium and embryo (2,47,53) or changes to the hormonal milieu (3,26). Our results show that rhFSH alters the maternal environment so that pregnancy rates are reduced and fetal development perturbed.…”

Section: Discussionmentioning

confidence: 56%

“…It has been demonstrated in several species that endogenous ovarian hormone concentrations are altered by gonadotropin stimulation (17,28,31,32), so it is likely that stimulation influences the uterus indirectly by altering estradiol and progesterone production. Changes in steroid hormone concentrations can also influence implantation rates and fetal development in the rat and sheep (3,26). Changes in the expression of steroid hormone receptors [which have been observed after gonadotropin stimulation in women (20,23,33,36)] may also influence endometrial receptivity, because they mediate cellular responses to those hormones.…”

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Recombinant human follicle-stimulating hormone alters maternal ovarian hormone concentrations and the uterus and perturbs fetal development in mice

Kelley

Kind

Lane

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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human follicle-stimulating hormone alters maternal ovarian hormone concentrations and the uterus and perturbs fetal development in mice. Am J Physiol Endocrinol Metab 291: E761-E770, 2006. First published May 23, 2006 doi:10.1152 doi:10. /ajpendo.00079.2006pins are routinely administered to produce multiple oocytes for clinical in vitro fertilization (IVF) treatment, laboratory research, and livestock industries. Studies in mice have shown gonadotropin stimulation using equine chorionic gonadotropin (eCG) affects the endometrium, implantation, and fetal development. Evidence from clinical studies also indicates that stimulation with recombinant human follicle-stimulating hormone (rhFSH) may be detrimental to the endometrium and implantation rates. We investigated the effect of rhFSH in mice on maternal plasma hormone concentrations and uterine gene and protein expression and the effect of a stimulated maternal environment on pregnancy. Adult females were stimulated with rhFSH or eCG, followed by human chorionic gonadotropin (hCG). On day 4 of pseudopregnancy, mice either had embryos transferred to the uterus or were killed, and blood and uterine samples were collected. Pregnancy outcomes were examined on day 15. Gonadotropin stimulation increased plasma progesterone concentrations on day 4 compared with controls, whereas estradiol concentrations were unaffected. Stimulation also reduced uterine leukemia inhibitory factor (Lif) mRNA, but the expression of estrogen and progesterone receptors (Esr1 and Pgr), homeobox gene Hoxa10, and Vegf mRNA were unchanged. Furthermore, distribution of uterine PGR protein expression was altered by stimulation, but LIF protein was unchanged. Stimulated embryo transfer recipients had lower pregnancy rates than controls, and fetuses from the rhFSH group had reduced weight, length, and maturity. These results demonstrate that gonadotropin stimulation with rhFSH or eCG alters the preimplantation maternal environment, which results in reduced pregnancy rates and fetal development in the mouse. endometrium; equine chorionic gonadotropin; ovarian stimulation; gonadotropin; mouse GONADOTROPIC HORMONES ARE routinely administered during in vitro fertilization (IVF) treatment to stimulate the ovaries to produce high numbers of oocytes. Typically, exogenous follicle-stimulating hormone (FSH) is used to mature multiple follicles, then human chorionic gonadotropin (hCG) mimics luteinizing hormone (LH) by inducing ovulation. Although this procedure is widely used in human IVF, laboratory research and livestock industries, the possible consequences of gonadotropin stimulation are largely unknown. Evidence from some studies indicates that stimulation before IVF causes endometrial abnormalities and may reduce implantation rates (6,13,33,34). Studies in mice have revealed that exogenous gonadotropins perturb embryo and oocyte development (15)(16)(17)(18)50) and cause changes to the mother (40, 44, 45), both of which contribute to reduced implantation rate, fetal development rate, and fetal weight (1...

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“…(McCarthy, 2008). In our model, we have chosen to use the estrogen, 17-b estradiol and the doses chosen are comparable to those used in other studies of sexual differentiation (Bartholomeusz et al, 1999;Patisaul et al, 2006).…”

Section: Preliminary Findings In An Animal Modelmentioning

confidence: 99%

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

Aiello

Whitaker‐Azmitia

2011

The Anatomical Record

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The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphicthe amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-b estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Anat Rec, 294:1663-1670, 2011. V V C 2011 Wiley-Liss, Inc.Key words: autism; oxytocin; cortisol; sexual differentiation; extreme male TWO HYPOTHESESSimply stated, the hypothesis which we are proposing in this article, and the work currently ongoing in our lab, is that enhanced sexual differentiation of the brain, towards the male phenotype, leads to changes in the neuroendocrine factors, oxytocin and cortisol. These factors are involved in the processing and evaluation of social bonding experiences and any disruption in their typical function can lead to the primary defining characteristic of the autism phenotype-inadequate social bonding. The Extreme Male Hypothesis of AutismAutism is a disorder of brain development and thus any factors which regulate brain development and are known to be altered in autism should be considered as possibly contributing to the phenotype. For example, much of our previous work and work of others, has focused on the known role of serotonin in brain development as well as the well known hyperserotonemia which occurs in autism (Whitaker-Azmitia, 2005). More recently, researchers have proposed a role for sexual differentiation of the brain in the phenotypic behaviors of

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Embryo Survival, and Fetal and Placental Growth Following Elevation of Maternal Estradiol Blood Concentrations in the Rat1

Cited by 37 publications

References 25 publications

Histopathological Effect of Ketoconazole on Rat Placenta

Histopathological Effect of Ketoconazole on Rat Placenta

Recombinant human follicle-stimulating hormone alters maternal ovarian hormone concentrations and the uterus and perturbs fetal development in mice

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

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