Effects of aroclor 1254 on the expression of the KAP3 gene and reproductive function in rats

2007 ◽  
Vol 19 (4) ◽  
pp. 539 ◽  
Author(s):  
Chae Kwan Lee ◽  
Han Seung Kang ◽  
Ju Ran Kim ◽  
Byung Ju Lee ◽  
Jong Tae Lee ◽  
...  
Keyword(s):  
Sexual Differentiation ◽  
Reproductive Function ◽  
Female Rats ◽  
Mrna Levels ◽  
Critical Periods ◽  
Control Groups ◽  
Control Male ◽  
Control Female ◽  
Male Control ◽  
Brain Sexual Differentiation

The present study investigated the effects of aroclor 1254 (A1254) on the expression of the kinesin superfamily associated protein 3 (KAP3) gene in F1 rat brain during brain sexual differentiation and puberty. In addition, the effects of A1254 on reproductive function were examined. The KAP3 gene is involved in the neurogenesis and synaptogenesis of sexual differentiation in rats and also during puberty. In the present study, pregnant Sprague–Dawley rats each received a daily dose of A1254 (0, 10, 50 mg kg–1) dissolved in 1.0 mL corn oil by gavage, from gestational Day (GD) 8 to postnatal Day (PD) 21. The mRNA levels of the KAP3 gene in hypothalamic tissues were analysed by northern blot hybridisation during the critical periods of brain sexual differentiation (GD18 and PD5) and puberty (PD28). Variables affecting reproduction in F1 female rats, such as vaginal opening (VO), vaginal oestrus (VE) and oestrous cyclicity, were recorded. Depending on the sex and A1254 exposure (control or 50 mg kg–1 day–1), F1 rats were divided into three mating groups, namely control male–control female, control male–A1254-treated female and A1254-treated male–control female. During the critical periods of brain sexual differentiation (GD18, PD5) and puberty (PD28), KAP3 mRNA levels were significantly reduced in A1254-treated fetal and pubertal rat brains relative to those of control groups. In A1254-treated F1 female rats, VO and VE were delayed, the percentage of irregular oestrous cycles was increased and the duration of the oestrous cycle was extended in a dose-dependent manner compared with control groups. Treatment with a high dose of A1254 significantly impaired the reproductive function of both male and female F1 rats, including mating and pregnancy indices and the number of live fetuses. These data suggest that A1254 disrupts transcriptional regulation of the KAP3 gene in fetal and pubertal rat brains and that these effects may be related to A1254-induced abnormal brain sexual differentiation and lowered reproductive function in F1 rats.

Effects of maternal exposure to an aromatase inhibitor on sexual behaviour and neurochemical and endocrine aspects of adult male rat

2008 ◽  
Vol 20 (5) ◽  
pp. 557 ◽  
Author(s):  
Daniela C. C. Gerardin ◽  
Renata C. Piffer ◽  
Patrícia C. Garcia ◽  
Estefânia G. Moreira ◽  
Oduvaldo C. M. Pereira
Keyword(s):  
Aromatase Inhibitor ◽  
Sexual Differentiation ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Anogenital Distance ◽  
Sexual Behaviours ◽  
Brain Sexual Differentiation ◽  
Adult Male Rat

The present study examined the effects of letrozole exposure during brain sexual differentiation on endocrine, behavioural and neurochemical parameters in male rat descendants. Pregnant female rats received 1 mg kg–1 day–1 letrozole or vehicle by oral gavage on gestational Days 21 and 22. Exposure to letrozole reduced anogenital distance in males on postnatal Day (PND) 22. At adulthood (PND 75), plasma testosterone levels and hypothalamic dopaminergic activity were increased, but sexual competence was impaired, because fewer successful sexual behaviours (mount, intromission and principally ejaculation) were observed. The impairment of reproductive function by prenatal exposure to an aromatase inhibitor reinforces the importance of adequate oestrogenic activity during perinatal sexual differentiation for complete masculinisation of the hypothalamus.

scholarly journals Programming of the reproductive axis by hormonal and genetic manipulation in mice

Reproduction ◽  
2018 ◽  
Author(s):  
Susana B Rulli ◽  
María Julia Cambiasso ◽  
Laura D Ratner
Keyword(s):  
Sex Chromosome ◽  
Genetic Manipulation ◽  
Sex Differentiation ◽  
Reproductive Function ◽  
Gonadal Steroids ◽  
Critical Periods ◽  
Female Reproduction ◽  
Control Male ◽  
Male And Female ◽  
The Brain

In mammals, the reproductive function is controlled by the hypothalamic-pituitary-gonadal axis. During development, mechanisms mediated by gonadal steroids exert an imprinting at the hypothalamic-pituitary level, by establishing sexual differences in the circuits that control male and female reproduction. In rodents, the testicular production of androgens increases drastically during the fetal/neonatal stage. This process is essential for the masculinization of the reproductive tract, genitals and brain. The conversion of androgens to estrogens in the brain is crucial for the male sexual differentiation and behavior. Conversely, feminization of the brain occurs in the absence of high levels of gonadal steroids during the perinatal period in females. Potential genetic contribution to the differentiation of brain cells through direct effects of genes located on sex chromosomes is also relevant. In this review, we will focus on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal axis of transgenic mice with persistently elevated expression of the human chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal steroids due to a constant hCG stimulation is able to disrupt the developmental programming of the hypothalamic-pituitary axis in both transgenic males and females. Locally produced estrogens by the hypothalamic aromatase might play a key role in the phenotype of these mice. The “four core genotypes” mouse model demonstrated a potential influence of sex chromosome genes in brain masculinization before critical periods of sex differentiation. Thus, hormonal and genetic factors interact to regulate the local production of the neurosteroids necessary for the programming of the male and female reproductive function.

scholarly journals Subchronic toxicity of aqueous extract of Alstonia boonei de wild. (apocynaceae) stem bark in normal rats

2015 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Barnabé Lucien Nkono Ya Nkono ◽  
Selestin Dongmo Sokeng ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Frida Longo ◽  
Pierre Kamtchouing
Keyword(s):  
Aqueous Extract ◽  
Biochemical Study ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Control Male ◽  
Control Female ◽  
Hematological Analysis ◽  
Wbc Count ◽  
Dose Dependent

<p><strong>Methodology:</strong> Wistar rats were randomly assigned into eight groups of five animals each: four male groups and four female groups. Each sex group had a control group receiving distilled water and three test groups receiving 200, 500 and 1000mg/kg respectively. Animal’s body weights were recorded on the first day and once a week for the four experiment weeks. The hematological analysis included total WBC count, total RBC count, Hb, %HCT, MCV, MCH and MCHC. Biochemical/serum profile studies include TG, TC, ALT, AST, urea and TP. Tissue specimens of the liver, kidney and lung were subjected to histological examination using standard hematoxylin-eosin staining.</p><p><strong>Results:</strong> In male rats, aqueous extract showed significant decreases in relative weight of liver with extreme significance P&lt;0.001 at a dose of 200mg/kg (vs. control group), P&lt;0.001 of lung at all the doses, P&lt;0.05 (200 and 500mg/kg) and P&lt;0.01 (1000mg/kg) in heart weight. In relative kidney weight, only the dose of 1000mg/kg showed a significant increase vs. normal control male rats. Unlike male rats, only relative kidney weight in female rats was significantly different from the control group in a dose-dependent manner. The aqueous extract treated male groups showed significant increases P&lt;0.001 (1000mg/kg) of total WBC count and MCHC, significant decreases of %HTC (dose response manner), P&lt;0.05 total RBC count (at doses of 500 and 1000mg/kg) and Hb P&lt;0.01 (500mg/kg) vs. normal male rats. In female rats, the haematological study showed significant increase P&lt;0.01 of total WBC count (at the doses of 500 and 1000mg/kg), significant decreases P&lt;0.05 and P&lt;0.01 of total RBC respectively at the doses of 200 and 1000mg/kg, significant decrease of Hb with extreme significance P&lt;0.001 at the dose 1000mg/kg, %HTC also decrease dose response manner vs. control female rats. Biochemical study showed in male rats significant decreases in level of TG P&lt;0.001 (at the doses of 200 and 500mg/kg) and urea, although it showed any dose-dependent effect vs. control male rats. AST also decreases (P&lt;0.05) in male rats at the dose of 200mg/kg but significantly increase P&lt;0.001 at the dose of 500mg/kg. In the female rats, biochemical study revealed significant increases in level of TG P&lt;0.001 and urea P&lt;0.01 at the dose of 200mg/kg and significant decreases in level of TG P&lt;0.01, AST P&lt;0.05 and urea P&lt;0.05 at the dose of 500mg/kg (vs. control female rats). Microscopically, there were mild hepatic and renal tissue injuries supporting the hematological analysis.</p><p><strong>Conclusion:</strong> The results indicated that aqueous extract of <em>Alstonia boonei</em> De Wild is toxic in high doses.</p>

Abstract 17462: Relevance of Regulatory T Cells to Gender Dimorphism in Pulmonary Hypertension

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Rasa Tamosiuniene ◽  
Linh Nguyen ◽  
Ayala Luria ◽  
Joshua Sante ◽  
Toshie Saito ◽  
...  
Keyword(s):  
T Cell ◽  
Vascular Wall ◽  
Reciprocal Relationship ◽  
Female Rats ◽  
Gender Dimorphism ◽  
Control Male ◽  
Control Female ◽  
Male And Female Rats ◽  
Endogenous Estrogen

Idiopathic Pulmonary Arterial Hypertension (IPAH) is a disease with female predominance. A growing body of evidence shows reciprocal relationship between sex steroids and the immune system. The aim of the present study was to determine whether the absence of Tregs with the presence of endogenous estrogen mediate the development of PH in a gender-specific manner and if protective signaling pathways of Tregs prevent gender dimorphism of PH susceptibility in T cell deficient animal model of PH. Methods and Results: in two utilized models of PH inbred Wag T cell deficient athymic (AT) nude male and female rats were given s/c SU5416 in normoxia or treated with chronic hypoxia (CH) for 21d. In IR experiments, AT rats received purified CD4+CD25+hi/Tregs. We also tested the effect of murine/human Tregs or CD4+CD25- on primary rat lung, cardiac and human lung microvascular ECs (RLMECs, HLMECs, RCMECs) with set-up of cocultures. In both PH models treatment resulted in development of PH with significantly higher RVSP and particular significantly pronounced RVH in female than in male in both SU5416 and CH groups (Fulton index: 0.41±0.01vs.0.33±0.02 and 0.52±0.03vs.0.37±0.01, p< 0.05). However, circulating estrogen levels were found to be significantly elevated in female than in male in all animal groups. For both female and male AT animals IR of Tregs prevented PH with RV remodeling, as well as decreased perivascular fibrosis and increased estrogen receptor (ER)β expression in lung and RV vascular wall. In vitro studies on coculture of Tregs with RLMECs and RCMECs resulted in an upregulation of IL-10, HO-1, PDL1, ERα, ERβ, activation of pAKT pathway, and endothelial nitric oxide synthase (eNOS), which was abrogated with ER antagonist ICI182,780. In addition, compared with control male AT rats, control female animals had increased expression of HO1, HO2 enzymes in lung and RV vascular wall endothelial/Reca+ cells as well as increased capillary density in RV. Thus, differential HO expression between the genders might account for the PH susceptibility. Conclusions: Our data suggest that Tregs signaling is required as a major mechanism with possible mutual interaction of endogenous estrogen to prevent endothelial injury related gender dimorphism for the development of PH.

scholarly journals Effect of GABA-T on Reproductive Function in Female Rats

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 567
Author(s):  
Wenyu Si ◽  
Hailing Li ◽  
Tiezhu Kang ◽  
Jing Ye ◽  
Zhiqiu Yao ◽  
...  
Keyword(s):  
Mrna Level ◽  
Reproductive Function ◽  
Female Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Lactation Performance ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Expression Of Genes

This study explored the role of γ-aminobutyric acid transaminase (GABA-T) in the puberty and reproductive performance of female rats. Immunofluorescence technique, quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution of GABA-T and the expression of genes and hormones in female rats, respectively. The results showed that GABA-T was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and periventricular nucleus (PeN) of the hypothalamus, and in the adenohypophysis, ovarian granulosa cells and oocytes. Abat mRNA level at 28 d was lowest in the hypothalamus and the pituitary; at puberty, it was lowest in the ovary. Abat mRNA level was highest in adults in the hypothalamus; at infancy and puberty, it was highest in the pituitary; and at 21 d it was highest in the ovary. After vigabatrin (GABA-T irreversible inhibitor) was added to hypothalamus cells, the levels of Abat mRNA and Rfrp-3 mRNA were significantly reduced, but Gnrh mRNA increased at the dose of 25 and 50 μg/mL; Kiss1 mRNA was significantly increased but Gabbr1 mRNA was reduced at the 50 μg/mL dose. In prepubertal rats injected with vigabatrin, puberty onset was delayed. Abat mRNA, Kiss1 mRNA and Gnrh mRNA levels were significantly reduced, but Rfrp-3 mRNA level increased in the hypothalamus. Vigabatrin reduced the concentrations of GABA-T, luteinizing hormone (LH) and progesterone (P4), and the ovarian index. Lactation performance was reduced in adult rats with vigabatrin treatment. Four hours after vigabatrin injection, the concentrations of GABA-T and LH were significantly reduced in adult and 25 d rats, but follicle-stimulating hormone (FSH) increased in 25 d rats. In conclusion, GABA-T affects the reproductive function of female rats by regulating the levels of Gnrh, Kiss1 and Rfrp-3 in the hypothalamus as well as the concentrations of LH and P4.

scholarly journals Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3681-3691 ◽  
Author(s):  
Beverly S. Rubin ◽  
Jenny R. Lenkowski ◽  
Cheryl M. Schaeberle ◽  
Laura N. Vandenberg ◽  
Paul M. Ronsheim ◽  
...  
Keyword(s):  
Sex Differences ◽  
Bisphenol A ◽  
Brain Development ◽  
Sexual Differentiation ◽  
Female Offspring ◽  
Sexually Dimorphic ◽  
Critical Periods ◽  
Neuron Number ◽  
Brain Sexual Differentiation ◽  
Estrogenic Chemical

Humans are routinely exposed to bisphenol A (BPA), an estrogenic chemical present in food and beverage containers, dental composites, and many products in the home and workplace. BPA binds both classical nuclear estrogen receptors and facilitates membrane-initiated estrogenic effects. Here we explore the ability of environmentally relevant exposure to BPA to affect anatomical and functional measures of brain development and sexual differentiation. Anatomical evidence of alterations in brain sexual differentiation were examined in male and female offspring born to mouse dams exposed to 0, 25, or 250 ng BPA/kg body weight per day from the evening of d 8 of gestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hydroxylase (TH) neurons in the rostral periventricular preoptic area, an important brain region for estrous cyclicity and estrogen-positive feedback. The significant sex differences in TH neuron number observed in control offspring were diminished or obliterated in offspring exposed to BPA primarily because of a decline in TH neuron number in BPA-exposed females. As a functional endpoint of BPA action on brain sexual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Data from these studies revealed significant sex differences in the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capable of altering important events during critical periods of brain development.

scholarly journals Hypothalamic alterations in fetuses of high fat diet-fed obese female rats

2008 ◽  
Vol 200 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Anshu Gupta ◽  
Malathi Srinivasan ◽  
Supaporn Thamadilok ◽  
Mulchand S Patel
Keyword(s):  
Insulin Receptor ◽  
Insulin Signaling ◽  
Maternal Obesity ◽  
Late Gestation ◽  
Female Rats ◽  
Melanocortin Receptor ◽  
Mrna Levels ◽  
High Fat ◽  
Control Female ◽  
Protein Levels

The offspring of high fat (HF) diet-fed rats display increased body weight during adulthood. However, it is not known whether the changes in appetite regulation in these animals occur in utero or postnatally. We investigated the effects of maternal obesity induced by a HF diet prior to and during pregnancy on leptin and insulin signaling and the expression of orexigenic and anorexigenic peptides in term fetal hypothalami. The consumption of a HF diet prior to and during pregnancy resulted in obesity in HF female rats; additionally, HF female rats exhibited hyperinsulinemia and hyperleptinemia which were exaggerated in late gestation compared with control female rats that were fed a standard rodent laboratory chow (LC). Term fetuses of HF female rats (FHF) also had significantly higher serum leptin and insulin levels compared with control fetuses (FLC) while there was no difference in average fetal weight between the two groups. FHF hypothalami showed elevated levels of mRNA and proteins for leptin long receptor and insulin receptor β-subunit. However, the protein levels of signal transducers and activators of transcription-3 and insulin receptor substrate-2, the downstream signaling components of leptin and insulin signaling respectively were decreased. Also, FHF hypothalami had increased mRNA levels of neuropeptide Y and agouti-related polypeptide indicating that orexigenic neuropeptides in HF progeny are already upregulated by term fetal stage. Additionally, the mRNA levels of pro-opiatemelanocortin and melanocortin receptor-4 were also increased in the HF fetal hypothalami. These findings indicate potential programming effects of an altered intrauterine environment induced by HF diet consumption on appetite-regulating neuropeptides and leptin and insulin signaling in the late fetal period.

PEPTIDASE ACTIVITY IN THE HYPOTHALAMI OF RATS TREATED NEONATALLY WITH OESTROGEN

1973 ◽  
Vol 72 (1) ◽  
pp. 9-17 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper
Keyword(s):  
Sexual Differentiation ◽  
Critical Period ◽  
Testosterone Propionate ◽  
Marked Decrease ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Peptidase Activity ◽  
Rat Hypothalamus ◽  
Lh Secretion

ABSTRACT The previous paper (Griffiths & Hooper 1973) described the activity of certain hypothalamic peptidases following orchidectomy and testosterone propionate injection, and suggested that changes in enzyme levels may be used as an index of gonadotrophin release in male rats, in a similar way to that previously described for female rats (Griffiths & Hooper 1972a). Using this approach, the effect of neonatally administered oestrogen on the hypothalamus was investigated. The marked increase in supernatant activity in male rats and the equally marked decrease in supernatant activity in female rats, both injected during the critical period of hypothalamic sexual differentiation, are interpreted as indicating decreased LH secretion in males and increased LH secretion in females respectively. It can be concluded that the changes in reproductive function produced by neonatally administered oestrogen are caused by alterations in LH-RF metabolism and that the peptidases in the rat hypothalamus are responsible for this metabolism.

STUDIES OF SEXUAL DIFFERENTIATION OF SHEEP

1978 ◽  
Vol 89 (1) ◽  
pp. 182-189 ◽  
Author(s):  
P. R. Wilson ◽  
M. F. Tarttelin
Keyword(s):  
Blood Plasma ◽  
Sexual Differentiation ◽  
Female Offspring ◽  
Plasma Testosterone ◽  
Plasma Samples ◽  
Normal Appearance ◽  
Control Male ◽  
Control Female ◽  
Male And Female ◽  
Males And Females

ABSTRACT Forty ewes were given intramuscular injections of testosterone cypionate (200 mg) on each of the 20th, 27th and 40th days of gestation. This treatment ensured foetal exposure to testosterone from day 20 to day 65. Forty untreated ewes acted as controls. At birth, pre-natally androgenised male lambs were anatomically normal, but similarly treated female offspring displayed complete external genital masculinisation including the presence of a prepuce, penis and scrotum and the absence of an external vulval opening. No male gonads were present. Internally, the female lambs possessed ovaries, uteri, cervices and vagina of normal appearance. Two-weekly blood plasma samples were withdrawn from 10 androgenised and 6 control female offspring and 8 androgenised and 8 control male offspring from 4–30 weeks of age. Testosterone levels in males and LH levels in males and females were measured by radioimmunoassays. Analyses of variance showed that post-natal plasma LH levels in pre-natally androgenised lambs (male and female) were significantly depressed (P < 0.001), and that plasma testosterone concentrations in pre-natally androgenised males were subsequently depressed (P < 0.001). These results suggested that pre-natal androgenisation impaired hypothalamic hypophysiotrophic and/or pituitary function during the first 30 weeks of post-natal life which resulted either directly, or indirectly via reduced LH output, in a suppression of testosterone production by the testes.

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