Maternal aromatase inhibition via letrozole altered RFamide-related peptide-3 and gonadotropin releasing hormone expression in pubertal female rat

2021 ◽  
Author(s):  
Zahra Shaaban ◽  
Amin Tamadon ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Amin Derakhshanfar
Keyword(s):  
Body Weight ◽  
Polycystic Ovary ◽  
Body Weight Gain ◽  
Late Pregnancy ◽  
Serum Testosterone ◽  
Female Offspring ◽  
Female Rats ◽  
Female Rat ◽  
Sprague Dawley ◽  
Letrozole Treatment

Abstract Despite the prevalence of polycystic ovary syndrome (PCOS) among childbearing women and the development of many animal models for this syndrome, information on its etiology is still scarce. Intrauterine hyperandrogenic environment may underlie changes at the levels of hypothalamus, pituitary and ovary organization in female offspring, and PCOS later in life. Letrozole, has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, the aim of this research was to assess the condition in a prenatal letrozole-treated rat model. Twenty-eight female rats from dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n = 21) received letrozole treatment on days 16–18 gestation at doses 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW). Prenatal letrozole-treatment delayed parturition time and reduced the litter size in pregnant dams (P < 0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, and serum testosterone concentration and reduced estradiol levels (P < 0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, Letrozole at 1.25 and 1 mg/kg BW showed increased Rfrp and decreased Gnrh mRNA expression (P < 0.0001). Letrozole treatment at doses 1 mg/kg BW and lower was not feto-toxic. It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.

scholarly journals Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

2020 ◽  
Author(s):  
Zahra Shaaban ◽  
Amin Tamadon ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Amin Derakhshanfar
Keyword(s):  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Body Weight Gain ◽  
Late Pregnancy ◽  
Female Offspring ◽  
Female Rats ◽  
Sprague Dawley ◽  
Ovary Syndrome ◽  
Letrozole Treatment

Abstract Background: Despite the prevalence of polycystic ovary syndrome (PCOS) among childbearing women and the development of many animal models for this syndrome, information on its etiology is still scarce. Intrauterine hyperandrogenic environment may underlie changes at the levels of hypothalamus, pituitary and ovary organization in female offspring, and PCOS later in life. Letrozole, has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, the aim of this research was to assess the condition in a prenatal letrozole-treated rat model. Methods: Twenty-eight female rats from dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on days 16-18 gestation at doses 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW).Results: Prenatal letrozole-treatment delayed parturition time and reduced the litter size in pregnant dams (P<0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, and serum testosterone concentration and reduced estradiol levels (P<0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, Letrozole at 1.25 and 1 mg/kg BW showed increased Rfrp and decreased Gnrh mRNA expression (P<0.0001). Conclusions: Letrozole treatment at doses 1 mg/kg BW and lower was not feto-toxic. It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.

Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone

1993 ◽  
Vol 264 (6) ◽  
pp. E986-E992 ◽  
Author(s):  
J. C. Byatt ◽  
N. R. Staten ◽  
W. J. Salsgiver ◽  
J. G. Kostelc ◽  
R. J. Collier
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Mature Female ◽  
Female Rats ◽  
Bovine Growth Hormone ◽  
Female Rat ◽  
Moisture Percentage

Recombinant bovine prolactin (rbPRL) or bovine growth hormone (rbGH) was administered to mature female rats (10/treatment group) by daily subcutaneous injection for 10 days. Doses ranged from 7 to 5,000 micrograms/day (0.03-24 mg/kg body wt). Both rbPRL and rbGH increased body weight gain and food intake, but these parameters were increased at lower doses of rbPRL (7-63 micrograms/day) than rbGH (> 190 micrograms/day). Weight gain and food intake were maximally stimulated by 190 micrograms/day rbPRL, whereas maximal increased weight gain was obtained with the highest dose of rbGH (5,000 micrograms/day). Total carcass protein was increased by both hormones; however, protein as a percentage of body weight was unchanged. Similarly, neither rbPRL nor rbGH changed the percentage of carcass moisture. Percentage of body fat was increased by rbPRL but was decreased by rbGH. Weight of the gastrointestinal tract and kidneys was increased by both hormones, but increases were in proportion to body weight gain. These data confirm that ungulate prolactin is a hyperphagic agent in the female rat. In addition, they suggest that, while prolactin stimulates growth in mature female rats, this growth is probably not via a somatogenic mechanism.

scholarly journals A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

scholarly journals Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-Induced Polycystic Ovarian Syndrome With Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Yidong Xie ◽  
Li Xiao ◽  
Shangwei Li
Keyword(s):  
Insulin Resistance ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Body Weight Gain ◽  
Female Offspring ◽  
Female Rats ◽  
Metabolic Characteristics ◽  
Continuous Release ◽  
Reproductive Endocrine ◽  
The Impact

The beneficial effects of metformin, especially its capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), explains why it is widely prescribed. However, its effect on the offspring of patients with PCOS remains uncertain. This study investigated the impact of metformin treatment on the first- and second-generation female offspring born to letrozole-induced PCOS-IR rats. Forty-five female Wistar rats were implanted with continuous-release letrozole pellets or placebo and treated with metformin or vehicle control. Rats exposed to letrozole showed PCOS-like reproductive, endocrine, and metabolic phenotypes in contrast to the controls. Metformin significantly decreased the risk of body weight gain and increased INSR expression in F1 female offspring in PCOS-IR rats, contributing to the improvement in obesity, hyperinsulinemia, and IR. Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS. Nevertheless, we found no significant differences in INSR, FSHR, and LHCGR expression or other PCOS phenotypes in F2 female offspring of PCOS-IR rats. These findings indicated widespread reproductive, endocrine, and metabolic changes in the PCOS-IR rat model, but the PCOS phenotypes could not be stably inherited by the next generations. Metformin might have contributed to the improvement in obesity, hyperinsulinemia, and IR in F1 female offspring. The results of this study could be used as a theoretical basis in support of using metformin in the treatment of PCOS-IR patients.

scholarly journals Maternal Chronodisruption Throughout Pregnancy Impairs Glucose Homeostasis and Adipose Tissue Physiology in the Male Rat Offspring

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Halabi ◽  
Hans G. Richter ◽  
Natalia Mendez ◽  
Thilo Kähne ◽  
Carlos Spichiger ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Tissue Response ◽  
Female Rats ◽  
Male Rat ◽  
Standard Diet ◽  
Sprague Dawley

Compelling evidence in rats support the idea that gestational chronodisruption induces major changes in maternal circadian rhythms and fetal development and that these changes impact adult life at many physiological levels. Using a model of chronic photoperiod shifting throughout gestation (CPS), in which pregnant female rats (Sprague–Dawley strain; n = 16 per group) were exposed to lighting schedule manipulation every 3–4 days reversing the photoperiod completely or light/dark photoperiod (12/12; LD), we explored in the adult rat male offspring body weight gain, glucose homeostasis, adipose tissue content, adipose tissue response to norepinephrine (NE), and adipose tissue proteomic in the basal condition with standard diet (SD) and in response to high-fat diet (HFD). In adult CPS male (100–200 days old; n = 8 per group), we found increasing body weight, under SD and adiposity. Also, we found an increased response to intraperitoneal glucose (IGTT). After 12 weeks of HFD, white adipose tissue depots in CPS offspring were increased further, and higher IGTT and lower intraperitoneal insulin tolerance response were found, despite the lack of changes in food intake. In in vitro experiments, we observed that adipose tissue (WAT and BAT) glycerol response to NE from CPS offspring was decreased, and it was completely abolished by HFD. At the proteomic level, in CPS adipose tissue, 275 proteins displayed differential expression, compared with LD animals fed with a standard diet. Interestingly, CPS offspring and LD fed with HFD showed 20 proteins in common (2 upregulated and 18 downregulated). Based on these common proteins, the IPA analysis found that two functional pathways were significantly altered by CPS: network 1 (AKT/ERK) and network 2 (TNF/IL4; data are available via ProteomeXchange with identifier PXD026315). The present data show that gestational chronodisruption induced deleterious effects in adipose tissue recruitment and function, supporting the idea that adipose tissue function was programmed in utero by gestational chronodisruption, inducing deficient metabolic responses that persist into adulthood.

Abstract 245: Role Of Melanocortin-4-receptor In The Blood Pressure Regulation In Female Hyperandrogenemic Rats, A Model Of Polycystic Ovary Syndrome

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Roberta Lima ◽  
Jussara M do Carmo ◽  
Alexander Da Silva ◽  
John E Hall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Food Intake ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Sprague Dawley ◽  
Ovary Syndrome ◽  
Melanocortin 4 Receptor ◽  
Ad Libitum

Women with polycystic ovary syndrome (PCOS) are characterized by hyperandrogenemia, hirsutism, infertility, and enlarged cystic ovaries. Obesity and hypertension are also frequently found in women with PCOS, although the mechanisms responsible for the elevated blood pressure (BP) are unclear. Thus we tested the hypothesis that the melanocortin-4 receptor (MC4R), known to contribute to obesity hypertension in males, contributes to the elevated BP in hyperandrogenemic female rats, a model of PCOS. Female Sprague Dawley rats (4 wks) were implanted with dihydrotestosterone (DHT; 7.5mg/90 days sc) or placebo pellets (PL) (n=5/grp) and aged to 12 wks. Body weight and food intake (whether rats were pair fed or had ad libitum access) were measured daily. Two wks following implantation of radiotelemetry transmitters and intracerebroventricular cannulae, baseline mean arterial pressure (MAP) was measured for 5 days; then rats received MC3/4R antagonist, SHU-9119 (SHU; 1 nmol/h ICV) or vehicle for 7 days and MAP was recorded. DHT-treated rats had higher body weight and MAP than PL rats (BW: PL: 266.0±8.7; DHT: 348.5±10.4 g, p<0.01; MAP: PL rats: 102±5; DHT: 114±5 mmHg, p<0.05). SHU significantly increased food intake and body weights in both placebo (PL) and DHT-treated rats fed ad libitum (PL: 379.2±28.5; DHT: 451/3±7.3 g, p<0.01 DHT vs PL; 0.01 SHU vs control), but had no effect on MAP compared to controls (PL: 104±5; HAF rats: 114±5 mmHg; p<0.05, HAF vs PL; p=NS, SHU vs controls). However, in other rats, when pair fed with little increase in body weight (PL: 253.7±2.0, SHU: 261.0±0.6, p<0.05; DHT: 306.7±2.6, SHU: 316.7±1.5 g, p<0.05), SHU decreased MAP in DHT treated rats but not placebo controls (PL rats: 102±1, SHU: 103±2 mmHg; p=NS; DHT rats: 110±1 vs. SHU: 97±1 mmHg; p<0.001). Thus MC4R antagonist reduces MAP in DHT-treated rats only when food intake and body weight are controlled. These data suggest that activation of MC4R contributes to elevated BP in our model of PCOS and may also contribute to the elevated BP in women with PCOS. Supported by NIH R01HL66072, P01HL05971 and AHA 14POST18640015.

scholarly journals Cannabinoid-1 receptor antagonists reduce caloric intake by decreasing palatable diet selection in a novel dessert protocol in female rats

2008 ◽  
Vol 295 (1) ◽  
pp. R67-R75 ◽  
Author(s):  
Clare M. Mathes ◽  
Marco Ferrara ◽  
Neil E. Rowland
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
Diet Selection ◽  
Female Rats ◽  
Sprague Dawley ◽  
Receptor Antagonists ◽  
Sprague Dawley Rats ◽  
Cb1 Receptor Antagonists

Although many feeding protocols induce obesity, few use multiple foods to analyze diet selection within a single group of animals. To this end, we describe a protocol using time-limited access to a dessert that induces hyperphagia and body weight gain while allowing simple analysis of diet selection. Female retired breeder Sprague-Dawley rats were provided with ad libitum access to standard moist chow (1.67 kcal/g) and daily 8-h nocturnal access to either a sugar gel (SG; 0.31 kcal/g) or sugar fat whip (SFW; 7.35 kcal/g) for 15 days, and food intake and body weight were measured daily. Rats given SFW reduced moist chow intake but not enough to compensate for the large amount of calories consumed from SFW, and thus gained weight. We use this SFW overconsumption protocol to investigate the hypothesis that cannabinoid (CB)1 receptor antagonists reduce caloric intake by selectively decreasing consumption of palatable foods. In two experiments, female retired breeder Sprague-Dawley rats were injected with either Rimonabant (1 mg/kg ip) or vehicle (equal parts polyethylene glycol and saline, 1 ml/kg ip) for 7 days, or one of three doses of AM251 (0.3, 1.0, or 3.0 mg/kg ip), or vehicle for 15 days; food intake and body weight were measured daily. Both Rimonabant and AM251 decreased 24-h caloric intake, but the reduction was specific to a decrease in SFW consumption. This supports the hypothesis that these CB1 receptor antagonists impact feeding by modulating the perception of palatability.

scholarly journals Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life

2015 ◽  
Vol 224 (3) ◽  
pp. 245-259 ◽  
Author(s):  
Elisa Keating ◽  
Ana Correia-Branco ◽  
João R Araújo ◽  
Manuela Meireles ◽  
Rita Fernandes ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Body Weight Gain ◽  
Female Offspring ◽  
Metabolic Phenotype ◽  
High Dose ◽  
Metabolic Dysfunction ◽  
Sprague Dawley ◽  
Female Progeny ◽  
Insulin Resistant

The aim of this study was to understand whether high folic acid (HFA) exposure during the perigestational period induces metabolic dysfunction in the offspring, later in life. To do this, female Sprague–Dawley rats (G0) were administered a dose of folic acid (FA) recommended for pregnancy (control, C, 2 mg FA/kg of diet,n=5) or a high dose of FA (HFA, 40 mg FA/kg of diet,n=5). Supplementation began at mating and lasted throughout pregnancy and lactation. Body weight and food and fluid intake were monitored in G0 and their offspring (G1) till G1 were 13 months of age. Metabolic blood profiles were assessed in G1 at 3 and 13 months of age (3M and 13M respectively). Both G0 and G1 HFA females had increased body weight gain when compared with controls, particularly 22 (G0) and 10 (G1) weeks after FA supplementation had been stopped. G1 female offspring of HFA mothers had increased glycemia at 3M, and both female and male G1 offspring of HFA mothers had decreased glucose tolerance at 13M, when compared with matched controls. At 13M, G1 female offspring of HFA mothers had increased insulin and decreased adiponectin levels, and G1 male offspring of HFA mothers had increased levels of leptin, when compared with matched controls. In addition, feeding of fructose to adult offspring revealed that perigestational exposure to HFA renders female progeny more susceptible to developing metabolic unbalance upon such a challenge. The results of this work indicate that perigestational HFA exposure the affects long-term metabolic phenotype of the offspring, predisposing them to an insulin-resistant state.

Effect of Fetal and Neonatal Hypothyroidism on Glucose Tolerance in Middle-Aged Female Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Sajad Jeddi ◽  
Saeedeh Khalifi ◽  
Mahboubeh Ghanbari ◽  
Asghar Ghasemi
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Female Offspring ◽  
Female Rats ◽  
Control Group ◽  
Female Rat ◽  
Middle Aged ◽  
Intravenous Glucose ◽  
Neonatal Hypothyroidism ◽  
Glucose Levels

Background and objective: The effects of hypothyroidism during pregnancy and lactation on carbohydrate metabolism have been mostly studied in male animals. The aim of this study is therefore to investigate effect of fetal and neonatal hypothyroidism (FH and NH) on the glucose tolerance in middle-aged female rat offspring. Methods: Pregnant female rats were divided into three groups: Rats in the control group consumed tap water, while those in the FH and NH groups consumed 250 mg/L of 6-propyl-2-thiouracil (PTU) in their drinking water during gestation or lactation periods, respectively. After weaning, the female offspring were separated and divided into 3 groups (n=8/group): Control, FH, and NH. Body weight was recorded monthly and intravenous glucose tolerance test (IVGTT) was performed at month 12. Results: Compared to controls, female rats in the FH group had significantly higher plasma glucose levels than controls throughout the IVGTT except at min 60. Values at min 5 of the FH and control group were 196.1±1.9 and 155.3±5.9 mg/dL, respectively (P<0.05). In the NH group, plasma glucose levels were significantly higher only at min 5 (185.7±14.1 vs. 155.3±5.9 mg/dL, P<0.05). Conclusion: Hypothyroidism during fetal or neonatal periods caused glucose intolerance in middle-aged female offspring rats.

Effects of the lipase inhibitor orlistat on intake and preference for dietary fat in rats

1996 ◽  
Vol 271 (1) ◽  
pp. R48-R54 ◽  
Author(s):  
K. Ackroff ◽  
A. Sclafani
Keyword(s):  
Body Weight ◽  
Dietary Fat ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
Female Rats ◽  
Control Group ◽  
Fat Intake ◽  
Fat Absorption ◽  
Drug Induced ◽  
Dietary Fat Intake

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.

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