scholarly journals Maternal Perinatal Undernutrition Drastically Reduces Postnatal Leptin Surge and Affects the Development of Arcuate Nucleus Proopiomelanocortin Neurons in Neonatal Male Rat Pups

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 470-475 ◽  
Author(s):  
Fabien Delahaye ◽  
Christophe Breton ◽  
Pierre-Yves Risold ◽  
Mihaela Enache ◽  
Isabelle Dutriez-Casteloot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Metabolic Disorders ◽  
Arcuate Nucleus ◽  
Nerve Fibers ◽  
Male Rats ◽  
Male Rat ◽  
Maternal Undernutrition ◽  
Rat Pups ◽  
Plasma Leptin

A growing body of evidence suggests that maternal undernutrition sensitizes the offspring to the development of energy balance metabolic disorders such as type 2 diabetes, dyslipidemia, and obesity. The present study aimed at examining the impact of maternal undernutrition on leptin plasma levels in newborn male rats and on the arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons that are major leptin targets. Using a model of perinatal maternal 50% food-restricted diet (FR50) in the rat, we evaluated leptin plasma levels and hypothalamic POMC and NPY gene expression from postnatal day (PND) 4 to PND30 in both control and FR50 offspring. In control rats, a postnatal peak of plasma leptin was observed between PND4 and PND14 that reached a maximal value at PND10 (5.17 ± 0.53 ng/ml), whereas it was dramatically reduced in FR50 pups with the higher concentration at PND7 (0.93 ± 0.23 ng/ml). In FR50 animals, using semiquantitative RT-PCR and in situ hybridization, we showed that the hypothalamic POMC mRNA level was decreased from PND14 until PND30, whereas NPY gene expression was not significantly modified. In PND21 FR50 animals, we observed strikingly reduced immunoreactive β-endorphin nerve fibers projecting to the hypothalamic paraventricular nucleus without affecting NPY projections. Our data showed that maternal undernutrition drastically reduces the postnatal surge of plasma leptin, disturbing particularly the hypothalamic wiring as well as the gene expression of the anorexigenic POMC neurons in male rat pups. These alterations might contribute to the adult metabolic disorders resulting from perinatal growth retardation.

CONCENTRATIONS OF TESTOSTERONE IN NEONATAL MALE RATS SUCKLED NATURALLY AND HAND-FED

1982 ◽  
Vol 92 (3) ◽  
pp. 419-424 ◽  
Author(s):  
P. J. B. ANDERSON ◽  
A. E. FATINIKUN ◽  
A. D. SWIFT
Keyword(s):  
Human Milk ◽  
Plasma Levels ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Milk Replacer ◽  
Testosterone Concentration ◽  
Rat Pups ◽  
Lh Rh ◽  
Lh Releasing Hormone

Concentrations of testosterone were measured daily in plasma of neonatal male rats from the day of birth for 7 days. It was found that a significant (P <0·001) increase in mean plasma levels of testosterone occurs on day 2 of life, followed by a decrease on day 3. Separation of male rat pups from their mothers on the second day of life for as little as 2 h was associated with a significant (P <0·001) fall in plasma testosterone concentration. Hand-feeding the pups with a proprietary human milk substitute (milk-replacer) from birth until the expected time of the testosterone peak resulted in no increase in plasma levels of testosterone; inclusion of an antiserum to LH-releasing hormone (LH-RH) in the milk-replacer decreased the testosterone levels as did removing any supposed endogenous LH-RH in the milk replacer. Addition of a highly potent analogue of LH-RH, either in the presence or absence of the LH-RH antiserum, to the milk-replacer resulted in mean plasma levels of testosterone similar to those in naturally suckled rats. Rats fed with human milk showed an increase in plasma levels of testosterone. It is concluded that the increase in the plasma testosterone concentration found in male rat pups on the second day of life, which may have an important effect on the organization of the brain, is provoked indirectly by LH-RH ingested during suckling.

Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drug in utero

2003 ◽  
Vol 147 (1-2) ◽  
pp. 153-162 ◽  
Author(s):  
Pierre-Antoine H. Noailles ◽  
Kevin G. Becker ◽  
William H. Wood ◽  
Diane Teichberg ◽  
Jean-Lud Cadet
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
In Utero ◽  
Male Rat ◽  
Rat Pups

scholarly journals The Effect of Neonatal Maternal Stress on Plasma Levels of Adrenocorticotropic Hormone, Corticosterone, Leptin, and Ghrelin in Adult Male Rats Exposed to Acute Heterotypic Stressor

2016 ◽  
pp. S557-S566 ◽  
Author(s):  
A. HOLUBOVÁ ◽  
A. ŠTOFKOVÁ ◽  
J. JURČOVIČOVÁ ◽  
R. ŠLAMBEROVÁ
Keyword(s):  
Hpa Axis ◽  
Adult Male ◽  
Plasma Levels ◽  
Adrenocorticotropic Hormone ◽  
Acute Stress ◽  
Male Rats ◽  
Lower Sensitivity ◽  
Male Progeny ◽  
Swimming Stress ◽  
Plasma Leptin

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is important for maintenance of homeostasis during stress. Recent studies have shown a connection between the HPA axis and adipose tissue. The present study investigated the effect of acute heterotypic stress on plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), leptin, and ghrelin in adult male rats with respect to neonatal maternal social and physical stressors. Thirty rat mothers and sixty of their male progeny were used. Pups were divided into three groups: unstressed control (C), stressed by maternal social stressor (S), stressed by maternal social and physical stressors (SW). Levels of hormones were measured in adult male progeny following an acute swimming stress (10 min) or no stress. ELISA immunoassay was used to measured hormones. The ACTH and CORT levels were significantly increased in all groups of adult progeny after acute stress; however, CORT levels were significantly lower in both neonatally stressed groups compared to controls. After acute stress, plasma leptin levels were decreased in the C and SW groups but increased in the S group. The data suggest that long-term neonatal stressors lead to lower sensitivity of ACTH receptors in the adrenal cortex, which could be a sign of stress adaptation in adulthood. Acute stress in adult male rats changes plasma levels of leptin differently relative to social or physical neonatal stressors.

In utero exposure to dicyclohexyl and di-n-hexyl phthalate possess genotoxic effects on testicular cells of male rats after birth in the comet and TUNEL assays

2013 ◽  
Vol 33 (3) ◽  
pp. 230-239 ◽  
Author(s):  
M A Ahbab ◽  
Ü Ündeğer ◽  
N Barlas ◽  
N Başaran
Keyword(s):  
Comet Assay ◽  
Corn Oil ◽  
Tail Length ◽  
Male Rats ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Male Rat ◽  
Control Group ◽  
Pregnant Rats ◽  
Rat Pups ◽  
Testicular Cells

Phthalates are diester derivatives of phthalic acid widely used in many commercial applications. The aim of this study is therefore to evaluate possible genotoxicity of di- n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) at different concentrations using single-cell gel electrophoresis (comet) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling (TUNEL) assays in testes samples of male rat pups. DCHP and DHP in corn oil were administered to the pregnant rats by gavage at the doses of 0 (vehicle), 20, 100, and 500 mg kg−1 day−1 from gestational day 6 (GD6) to GD19. After delivery, male rats were allowed to grow until prepubertal, pubertal, and adulthood. At necropsy, the blood samples were collected from heart and were excised immediately. The apoptotic cells of prepubertal, pubertal, and adult testis were detected using TUNEL assay. The comet assay was performed on blood lymphocytes and testes samples of adult male rats. The comet assay results showed that tail length, tail intensity, olive tail moment (OTM), and percentage of DNA present in tail were higher when DHP content was increased. Judging from the values of OTM and percentage of DNA, DHP could significantly induce DNA breakage at doses of 100 and 500 mg kg−1 day−1 compared with the control group. An increase in TUNEL-positive cells of prepubertal, pubertal, and adult testicular cells was observed in the treated groups. In conclusion, prenatal exposure to DHP and DCHP may possess genotoxic risk to testicular cells of rats at all stages of development, even at adulthood.

scholarly journals Chronic Blockade of the Melanocortin 4 Receptor Subtype Leads to Obesity Independently of Neuropeptide Y Action, with No Adverse Effects on the Gonadotropic and Somatotropic Axes**This work was supported by grants from the Swiss National Research Science Foundation (31–39729-93, 31–55732-98, and 32–04912 3–97) and in part by Ferring Pharmaceuticals Ltd. Research Laboratories.

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4419-4427 ◽  
Author(s):  
Paula D. Raposinho ◽  
Einar Castillo ◽  
Violaine D’alleves ◽  
Pierre Broqua ◽  
François P. Pralong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuropeptide Y ◽  
High Plasma ◽  
Male Rats ◽  
Receptor Subtype ◽  
Somatotropic Axis ◽  
Intracerebroventricular Infusion ◽  
Melanocortin 4 Receptor ◽  
Chronic Infusion ◽  
Plasma Leptin

Abstract Neuropeptide Y (NPY) is a powerful orexigenic factor, and αMSH is a melanocortin (MC) peptide that induces satiety by activating the MC4 receptor subtype. Genetic models with disruption of MC4 receptor signaling are associated with obesity. In the present study, a 7-day intracerebroventricular infusion to male rats of either the MC receptor antagonist SHU9119 or porcine NPY (10 nmol/day) was shown to strongly stimulate food and water intake and to markedly increase fat pad mass. Very high plasma leptin levels were found in NPY-treated rats (27.1 ± 1.8 ng/ml compared with 9.9 ± 0.9 ng/ml in SHU9119-treated animals and 2.1 ± 0.2 ng/ml in controls). As expected, NPY infusion induced hypogonadism, characterized by an impressive decrease in seminal vesicle and prostate weights. No such effects were seen with the SHU9119 infusion. Similarly, whereas the somatotropic axis of NPY-treated rats was fully inhibited, this axis was normally activated in the obese SHU9119-treated rats. Chronic infusion of SHU9119 strikingly reduced hypothalamic gene expression for NPY (65.2 ± 3.6% of controls), whereas gene expression for POMC was increased (170 ± 19%). NPY infusion decreased hypothalamic gene expression for both POMC and NPY (70 ± 9% and 75.4 ± 9.5%, respectively). In summary, blockade of the MC4 receptor subtype by SHU9119 was able to generate an obesity syndrome with no apparent side-effects on the reproductive and somatotropic axes. In this situation, it is unlikely that hyperphagia was driven by increased NPY release, because hypothalamic NPY gene expression was markedly reduced, suggesting that hyperphagia mainly resulted from loss of the satiety signal driven by MC peptides. NPY infusion produced hypogonadism and hyposomatotropism in the face of markedly elevated plasma leptin levels and an important reduction in hypothalamic POMC synthesis. In this situation NPY probably acted both by exacerbating food intake through Y receptors and by reducing the satiety signal driven by MC peptides.

Gonadotrophin-releasing hormone regulation of gonadotrophin subunit gene expression: studies in tri-iodothyronine-suppressed rats

1989 ◽  
Vol 122 (1) ◽  
pp. 117-125 ◽  
Author(s):  
D. J. Haisenleder ◽  
G. A. Ortolano ◽  
A. C. Dalkin ◽  
S. J. Paul ◽  
W. W. Chin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blot Hybridization ◽  
Male Rats ◽  
Male Rat ◽  
Mrna Levels ◽  
Dot Blot ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Prolactin Mrna

ABSTRACT We have previously shown that a pulsatile gonadotrophin-releasing hormone (GnRH) stimulus can increase steady-state levels of α and LH-β subunit mRNAs in the male rat pituitary. Since α subunit is produced in both thyrotroph and gonadotroph cells, the effect of GnRH specifically on gonadotroph α gene expression is uncertain. To address this tissue, adult male rats were given injections of tri-iodothyronine (T3; 20 μg/100 g body wt, i.p.) daily for 8 days (day 8 = day of death) in order to decrease thyrotroph α mRNA levels (+ T3 group). Saline injections (i.p.) were given to control animals (− T3 group). Three days before GnRH administration, the animals were castrated and testosterone implants inserted s.c., to inhibit endogenous GnRH secretion. GnRH pulses (25 ng/pulse; 30-min interval) were given to freely moving animals (saline pulses to controls) via an atrial cannula for 12, 24 or 48 h. Serum LH and FSH were measured before and 20 min after the last GnRH pulse. Pituitary RNA was extracted and α, LH-β, FSH-β and prolactin mRNA levels were determined by dot-blot hybridization using 32P-labelled cDNA probes. Castration and testosterone replacement reduced α and LH-β mRNA levels by 30 and 40% respectively, compared with levels in untreated intact males, but did not decrease FSH-β concentrations. T3 administration further decreased α mRNA to 30% of values seen in intact males, but LH-β mRNA levels were unchanged. FSH-β mRNA concentrations were decreased by 23% in T3-treated rats (P < 0·05 vs intact controls). In −T3 rats, 12 h of GnRH pulses increased FSH-β mRNA levels (twofold) vs saline-pulsed controls, but significant increases in α or LH-β mRNA levels were not seen until after 24 h of GnRH pulses. In the +T3 group, an increase in α mRNA was observed earlier, after 12 h of GnRH pulses. After 24 and 48 h of GnRH, the increments in α and LH-β were of similar magnitude in both the +T3 and − T3 groups (4–5 and 3–4 fold increases in α and LH-β respectively; P < 0·05 vs saline-pulsed controls). In contrast, the stimulatory effect of GnRH on FSH-β mRNA was lost in + T3 animals after 48 h of pulses. In order to examine whether this loss in FSH-β mRNA responsiveness to GnRH was related to an inhibitory interaction of T3 in the presence of testosterone, a second study was conducted in castrated animals. The results showed that α mRNA levels were decreased by 33% in +T3 compared with −T3 castrated animals (P < 0·05), but LH-β and FSH-β mRNAs were unaffected by T3 administration. In castrated animals given GnRH pulses, T3 inhibited subunit mRNA responses and this effect was most marked for FSH-β mRNA. In contrast, prolactin mRNA levels were significantly higher (P < 0·05) in all +T3 experimental groups compared with their −T3 controls. These data indicate that T3 can inhibit FSH-β mRNA responses to pulsatile GnRH and that this action occurs in the absence of testosterone. Journal of Endocrinology (1989) 122, 117–125

Maternal prenatal undernutrition programs adipose tissue gene expression in adult male rat offspring under high-fat diet

2011 ◽  
Vol 301 (3) ◽  
pp. E548-E559 ◽  
Author(s):  
Marie-Amélie Lukaszewski ◽  
Sylvain Mayeur ◽  
Isabelle Fajardy ◽  
Fabien Delahaye ◽  
Isabelle Dutriez-Casteloot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
The Body ◽  
Male Rat ◽  
Adult Offspring ◽  
High Fat ◽  
Maternal Undernutrition ◽  
The Metabolic Syndrome ◽  
Leptin Sensitivity

Several studies have shown that maternal undernutrition leading to low birth weight predisposes offspring to the development of metabolic pathologies such as obesity. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we evaluated whether postweaning high-fat (HF) diet would amplify the phenotype observed under standard diet. We investigated biological parameters as well as gene expression profile focusing on white adipose tissues (WAT) of adult offspring. FR30 procedure does not worsen the metabolic syndrome features induced by HF diet. However, FR30HF rats displayed catch-up growth to match the body weight of adult control HF animals, suggesting an increase of adiposity while showing hyperleptinemia and a blunted increase of corticosterone. Using quantitative RT-PCR array, we demonstrated that FR30HF rats exhibited leptin and Ob-Rb as well as many peptide precursor and receptor gene expression variations in WAT. We also showed that the expression of genes involved in adipogenesis was modified in FR30HF animals in a depot-specific manner. We observed an opposite variation of STAT3 phosphorylation levels, suggesting that leptin sensitivity is modified in WAT adult FR30 offspring. We demonstrated that 11β-HSD1, 11β-HSD2, GR, and MR genes are coexpressed in WAT and that FR30 procedure modifies gene expression levels, especially under HF diet. In particular, level variation of 11β-HSD2, whose protein expression was detected by Western blotting, may represent a novel mechanism that may affect WAT glucocorticoid sensitivity. Data suggest that maternal undernutrition differently programs the adult offspring WAT gene expression profile that may predispose for altered fat deposition.

Sign in / Sign up

Export Citation Format

Share Document