Prenatal Inflammation Dampens Neurogenesis and Enhances Serotonin Transporter Expression in the Hippocampus of Adult Female Rats

Background/Aims: Prenatal exposure to lipopolysaccharide (LPS) dampens hippocampal neurogenesis. This effect is associated with increased anxiety-like behavior in adult offspring. Furthermore, blocking serotonin transporters (SERT) promotes adult neurogenesis. Previous studies were performed largely in males. Therefore, we explored the impact of prenatal LPS on neurogenesis, SERT expression in the hippocampus, and anxiety-like behavior in female rats during prepubertal and adulthood stages. Materials and Methods: Timed pregnant rats were injected with either saline or LPS (100 µg/kg, i.p.) on gestational days 15, 17, and 19. Newly born neurons were monitored by immunohistochemistry, and anxiety-like behavior was monitored using the elevated plus maze and open-field test. SERT expression in the hippocampus was assessed by Western blot and immunofluorescence. Results: Prenatal LPS led to reduced hippocampal neurogenesis in adult but not in prepubertal female offspring. This reduced neurogenesis was associated with enhanced hippocampal expression of SERT protein. However, there was no significant impact of prenatal LPS on anxiety-like behavior. Conclusions: Prenatal LPS-induced reduction in neurogenesis was dissociated from anxiety-like behavior in adult female rats. Furthermore, the long-lasting impact of prenatal LPS on neurogenesis in female offspring was age-dependent.

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METABOLISM OF 20β-HYDROXY-4-PREGNEN-3-ONE IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO

Acta Endocrinologica ◽

10.1530/acta.0.0830604 ◽

1976 ◽

Vol 83 (3) ◽

pp. 604-620 ◽

Cited By ~ 3

Author(s):

B. P. Lisboa ◽

M. Holtermann

Keyword(s):

Biological Activity ◽

Adult Female ◽

Female Rats ◽

Uterine Tissue ◽

Rat Uterus ◽

Adult Rats ◽

Pregnant Rats ◽

Progesterone Metabolites ◽

Ovariectomized Adult Rats

ABSTRACT In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20β-hydroxysteroid-oxidoreductase which catalyzes the conversion of 20β-hydroxy-4-pregnen-3-one to progesterone. Since a hepatic 20β-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20β-hydroxy-4-pregnen-3-one in these animals. Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20β-hydroxy-4-pregnen-3-one with uterine tissue: 20β-hydroxy-5α-pregnan-3-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3α,20β-diol, 4-pregnene-3α,20β-diol and 4-pregnene-3β,20β-diol. The conversion of 20β-hydroxy-4-pregnen-3-one to progesterone permits us to regard all five steroids isolated as progesterone metabolites in the rat uterus. 20β-hydroxy-5β-pregnan-3-one is the first C21-metabolite with a 5β(H)-configuration isolated in the rat uterus, which indicates the presence of 5β-reductase in this tissue.

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Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524922666211231095507 ◽

2021 ◽

Vol 22 ◽

Author(s):

Trina Sengupta ◽

Sutirtha Ghosh ◽

Archana Gaur T. ◽

Prasunpriya Nayak

Keyword(s):

Body Weight ◽

Young Adult ◽

Adult Female ◽

Developmental Stages ◽

Elevated Plus Maze ◽

Age Groups ◽

Female Rats ◽

Acute Exposure ◽

Adult Rats ◽

Plus Maze

Background: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium’s effect on anxiety in rodents at the different developmental stages is inconsistent. Aims: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. Objective: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. Methods: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. Results: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. Conclusion: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

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Modest maternal protein restriction fails to program adult hypertension in female rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00037.2003 ◽

2005 ◽

Vol 289 (4) ◽

pp. R1131-R1136 ◽

Cited By ~ 139

Author(s):

Lori L. Woods ◽

Julie R. Ingelfinger ◽

Ruth Rasch

Keyword(s):

Renin Angiotensin System ◽

Female Gender ◽

Female Offspring ◽

Protein Restriction ◽

Female Rats ◽

Male Rats ◽

Pregnant Rats ◽

Angiotensin System ◽

Low Protein ◽

Maternal Protein Restriction

Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50–65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 ± 3 mmHg vs. NP: 121 ± 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 ± 2,071 vs. NP: 26,248 ± 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 ± 0.11 106μm3, LP vs. NP: 1.07 ± 0.11 106μm3); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender.

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Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2007.05505.x ◽

2007 ◽

Vol 25 (8) ◽

pp. 2473-2482 ◽

Cited By ~ 69

Author(s):

Melissa J. Glenn ◽

Erin M. Gibson ◽

Elizabeth D. Kirby ◽

Tiffany J. Mellott ◽

Jan K. Blusztajn ◽

...

Keyword(s):

Adult Female ◽

Hippocampal Neurogenesis ◽

Female Rats

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SAT-717 Region-Specific Effects of the Exposome on Brain Monoamine Levels in Female Rats

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1863 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Amrita Kaimal ◽

Jessica Hooversmith ◽

Maryam H Al Mansi ◽

Philip V Holmes ◽

Sheba M J MohanKumar ◽

...

Keyword(s):

Prenatal Exposure ◽

Adult Female ◽

High Performance ◽

Endocrine Disrupting Chemicals ◽

Female Offspring ◽

Female Rats ◽

Saline Control ◽

Estradiol Treatment ◽

Specific Effects ◽

End Of Treatment

Abstract Prenatal programming with endocrine disrupting chemicals (EDCs), in particular the ubiquitous plasticizers bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP), can induce long-lasting behavioral changes in rats. Additionally, changes in estrogen are correlated with the development of mood disorders in women; however, the underlying neurobiological mechanisms are unclear. This study was conducted to determine the cumulative effects of prenatal exposure to EDCs followed by chronic estradiol treatment in adult female rats on monoamine levels in the prefrontal cortex (PFC) and hippocampus (HC). Dams were orally administered saline (control; 10 µL/kg), BPA (B; 5 µg/kg), DEHP (D; 7.5 mg/kg) or a combination of BPA+DEHP (B+D) during days 6 through 21 of pregnancy. Adult female offspring were sham-implanted or implanted with pellets that release 17β-estradiol (E2) for 90 days (20 ng/day; Innovative Research America). The offspring then underwent a battery of behavioral tests at the end of treatment. Brains collected from the offspring were sectioned and the PFC and HC were microdissected and analyzed for levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), using High-Performance Liquid Chromatography (HPLC). Significant reductions in monoamine levels were observed in the PFC while NE and 5-HT levels were markedly reduced in the HC after prenatal exposure to D or BD. BPA’s effects on monoamines were comparatively modest. E2 exposure increased DA but decreased 5-HT levels in the PFC of control animals. Prenatal exposure to EDCs made the offspring non-responsive to E2. The marked reduction in monoamine levels could have implications for learning and memory.

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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

Frontiers in Endocrinology ◽

10.3389/fendo.2021.701590 ◽

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.

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High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Nutrients ◽

10.3390/nu13010089 ◽

2020 ◽

Vol 13 (1) ◽

pp. 89

Author(s):

Soniya Xavier ◽

Jasmine Gili ◽

Peter McGowan ◽

Simin Younesi ◽

Paul F. A. Wright ◽

...

Keyword(s):

Maternal Diet ◽

Female Offspring ◽

Female Rats ◽

Omega 3 ◽

Male And Female ◽

Offspring Development ◽

Metabolic Outcomes ◽

Male And Female Rats ◽

The Impact

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.

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Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure

Journal of Endocrinology ◽

10.1677/joe.1.06506 ◽

2006 ◽

Vol 188 (3) ◽

pp. 435-442 ◽

Cited By ~ 31

Author(s):

P W F Hadoke ◽

R S Lindsay ◽

J R Seckl ◽

B R Walker ◽

C J Kenyon

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Adult Female ◽

Vascular Function ◽

Mesenteric Arteries ◽

Female Rats ◽

Control Group ◽

Pregnant Rats ◽

Vascular Contractility

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.

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