The Relation of Ovarian Steroid Levels in Young Female Rats to Subsequent Estrous Cyclicity and Reproductive Function during Aging1

Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.

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Immunotoxic Destruction of Distinct Catecholaminergic Neuron Populations Disrupts the Reproductive Response to Glucoprivation in Female Rats

Endocrinology ◽

10.1210/en.2003-0258 ◽

2003 ◽

Vol 144 (10) ◽

pp. 4325-4331 ◽

Cited By ~ 51

Author(s):

Helen I’Anson ◽

Lois A. Sundling ◽

Shannon M. Roland ◽

Sue Ritter

Keyword(s):

Cycle Length ◽

Reproductive Function ◽

Female Rats ◽

Estrous Cycles ◽

Neuron Populations ◽

Reproductive Response ◽

Estrous Cyclicity ◽

Catecholaminergic Neuron ◽

Catecholamine Neurons ◽

Glucoprivic Feeding

We tested the hypothesis that hindbrain catecholamine (norepinephrine or epinephrine) neurons, in addition to their essential role in glucoprivic feeding, are responsible for suppressing estrous cycles during chronic glucoprivation. Normally cycling female rats were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to monoclonal dopamine β-hydroxylase antibody (DSAP) into the paraventricular nucleus (PVN) of the hypothalamus to selectively destroy norepinephrine and epinephrine neurons projecting to the PVN. Controls were injected with unconjugated saporin. After recovery, we assessed the lesion effects on estrous cyclicity under basal conditions and found that DSAP did not alter estrous cycle length. Subsequently, we examined effects of chronic 2-deoxy-d-glucose-induced glucoprivation on cycle length. After two normal 4- to 5-d cycles, rats were injected with 2-deoxy-d-glucose (200 mg/kg every 6 h for 72 h) beginning 24 h after detection of estrus. Chronic glucoprivation increased cycle length in seven of eight unconjugated saporin rats but in only one of eight DSAP rats. Immunohistochemical results confirmed loss of dopamine β-hydroxylase immunoreactivity in PVN. Thus, hindbrain catecholamine neurons with projections to the PVN are required for inhibition of reproductive function during chronic glucose deficit but are not required for normal estrous cyclicity when metabolic fuels are in abundance.

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Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats

Endocrinology ◽

10.1210/en.2015-1740 ◽

2016 ◽

Vol 157 (5) ◽

pp. 2015-2027 ◽

Cited By ~ 24

Author(s):

Melinda A. Mittelman-Smith ◽

Sally J. Krajewski-Hall ◽

Nathaniel T. McMullen ◽

Naomi E. Rance

Keyword(s):

Arcuate Nucleus ◽

Hypogonadotropic Hypogonadism ◽

Reproductive Function ◽

Female Rats ◽

Lh Surge ◽

Serum Lh ◽

Estrous Cyclicity ◽

17Β Estradiol ◽

Neurokinin 3 Receptor ◽

Kndy Neurons

Abstract In the human infundibular (arcuate) nucleus, a subpopulation of neurons coexpress kisspeptin and neurokinin B (NKB), 2 peptides required for normal reproductive function. A homologous group of neurons exists in the arcuate nucleus of rodents, termed KNDy neurons based on the coexpression of kisspeptin, NKB, and dynorphin. To study their function, we recently developed a method to selectively ablate KNDy neurons using NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (SAP). Here, we ablated KNDy neurons in female rats to determine whether these neurons are required for estrous cyclicity and the steroid induced LH surge. NK3-SAP or Blank-SAP (control) was microinjected into the arcuate nucleus using stereotaxic surgery. After monitoring vaginal smears for 3–4 weeks, rats were ovariectomized and given 17β-estradiol and progesterone in a regimen that induced an afternoon LH surge. Rats were killed at the time of peak LH levels, and brains were harvested for NKB and dual labeled GnRH/Fos immunohistochemistry. In ovary-intact rats, ablation of KNDy neurons resulted in hypogonadotropic hypogonadism, characterized by low levels of serum LH, constant diestrus, ovarian atrophy with increased follicular atresia, and uterine atrophy. Surprisingly, the 17β-estradiol and progesterone-induced LH surge was 3 times higher in KNDy-ablated rats. Despite the marked increase in the magnitude of the LH surge, the number of GnRH or anterior ventral periventricular nucleus neurons expressing Fos was not significantly different between groups. Our studies show that KNDy neurons are essential for tonic levels of serum LH and estrous cyclicity and may play a role in limiting the magnitude of the LH surge.

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MODULATION OF TRIGLYCERIDES IN FEMALE RATTUS RATTUS WITH STEROID CONTRACEPTIVE ALGESTONE ACETOPHENIDE (DHPA)

FLORA AND FAUNA ◽

10.33451/florafauna.v25i1pp78-80 ◽

2019 ◽

Vol 25 (1) ◽

Author(s):

ASHOK KUMAR ◽

ALPANA PARMAR ◽

ANAND KUMAR BAJPEYEE

Keyword(s):

Mixed Type ◽

Rattus Rattus ◽

Young Female ◽

Female Rats ◽

Control Group ◽

Black Rat ◽

Long Acting ◽

Steroid Contraceptive

Young female Black rat (Rattus rattus), were administered monthly long acting steroid contraceptive to induce hypertriglyceridemia. It was observed that by 3 weeks of the second injection of estrogen containing mixed type of contraceptive, female rats developed consistent and frank hyperglyceridemia . TG in the treated rats was 195.8 ± 7.44 mg /100 ml as compared to 91.5 ± 6.27 mg/100ml in plasma of the control group.

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Effect of Exposure to Mixture of Heavy Metals Arsenic, Cadmium and Lead on Reproductive Function and Oxidative Stress in Female Rats

INTERNATIONAL JOURNAL OF TOXICOLOGICAL AND PHARMACOLOGICAL RESEARCH ◽

10.25258/ijtpr.v9i03.9075 ◽

2017 ◽

Vol 9 (03) ◽

Author(s):

Choudhuri D. ◽

Bhattacharjee T.

Keyword(s):

Oxidative Stress ◽

Heavy Metals ◽

Ascorbic Acid ◽

Reproductive Function ◽

Reproductive Organs ◽

Female Rats ◽

Corpora Lutea ◽

Oestrus Cycle ◽

Implantation Sites ◽

Live Fetus

Background : Toxicological consequences arising from exposure to mixtures of heavy metals especially at low, chronic and environmentally relevant doses are poorly recognised. In the present study, we evaluated effects of chronic exposure to combinations of three metals arsenic (As), cadmium (Cd) and lead (Pb) present frequently in drinking water on reproductive function and oxidative damage caused to reproductive organs of female rats. Method : Female rats were exposed to mixture of metals (As, Cdand Pb) for 90 consecutive days. The gain in body weight and weight of reproductive organs were recorded following autopsy on 91 stday. The oestrus cycle were monitored during entire treatment period. Numbers of corpora lutea, implantation sites, live fetus and survival of the fetus were evaluated in rats mated successfully with untreated male after completion of their respective treatment. Ovarian cholesterol, protein, ascorbic acid and enzyme Δ 5 -3β HSD levels were estimated. Serum levels of steroid hormones oestrogen and progesterone were estimated. Histopathological picture of both ovary and uterus were assessed. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidise (GPX) activity, amount of reduced glutathione (GSH) and malondyaldehyde (MDA) in blood, ovary and uterus were measured as biomarkers of oxidative stress. Results : The treated rats showed reduced body weight gain and reduction in the weight of ovary and uterus. Oestrus cycle was disrupted with continuous diestrous in treated animals. Number of corpora lutea, implantation sites and live fetus and the survival of fetus evaluate were reduced significantly in treated groups. The levels of ovarian cholesterol and ascorbic acid increased in treated rats with decrease Δ5 -3β HSD level. There was reduction in serum level of both the ovarian steroid hormones oestrogen and progesterone. The protein levels did not differ between the groups. There was a significant increase in levels of MDA and decrease in levels of all the antioxidant enzymes in treated group. Conclusion : The results revealed there was disruption to reproductive functions with decrease in stereoidogenic activity and associated oxidative stress in female rats treated with combination of mixture of metals (Cd, As and Pb) at low dose for 90 consecutive days.

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Assessment of Superoxide Dismutase and Catalase Evolution in Different Stages of an Experimental Endometriosis

Revista de Chimie ◽

10.37358/rc.17.6.5678 ◽

2017 ◽

Vol 68 (6) ◽

pp. 1381-1383

Author(s):

Allia Sindilar ◽

Carmen Lacramioara Zamfir ◽

Eusebiu Viorel Sindilar ◽

Alin Constantin Pinzariu ◽

Eduard Crauciuc ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Reproductive Function ◽

Female Rats ◽

Oxygen Species ◽

Efficient Treatment ◽

Endometrial Cells ◽

Gynecological Disorder ◽

The Impact

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.

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Marijuana and β-estradiol interactions on spatial learning and memory in young female rats: Lack of role of the G protein-coupled estrogen receptor (GPR30)

Life Sciences ◽

10.1016/j.lfs.2021.119723 ◽

2021 ◽

pp. 119723

Author(s):

Mohadeseh Chahkandi ◽

Gholamreza Komeili ◽

Gholamreza Sepehri ◽

Mohammad Khaksari ◽

Sedigheh Amiresmaili

Keyword(s):

Estrogen Receptor ◽

Learning And Memory ◽

G Protein ◽

Spatial Learning ◽

Young Female ◽

Female Rats ◽

Spatial Learning And Memory ◽

G Protein Coupled

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Protective Effects of Moderate Ca Supplementation against Cd-Induced Bone Damage under Different Population-Relevant Doses in Young Female Rats

Nutrients ◽

10.3390/nu11040849 ◽

2019 ◽

Vol 11 (4) ◽

pp. 849 ◽

Cited By ~ 3

Author(s):

Huang ◽

Liu ◽

Zhao ◽

Fu ◽

Wang ◽

...

Keyword(s):

Growth Factor ◽

Bone Formation ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Young Female ◽

Female Rats ◽

Bone Biomechanics ◽

Protective Effects ◽

Fibroblast Growth ◽

Bone Damage

Estimation of the skeleton-protective effects of Ca in Cd-induced bone damage is helpful in the assessment of Cd health risk. The aim of this study was to identify whether Ca supplementation during exposure to different population-relevant doses of Cd can prevent Cd-induced bone damage under the tolerable upper intake level of Ca supplementation. Young female Sprague-Dawley rats were given different population-relevant doses of Cd (1, 5, and 50 mg Cd/kg diet) and Ca supplementation (0.4% Ca supplementation) intervention. Ca supplementation significantly decreased Cd-induced bone microstructure damage, increased bone biomechanics (p < 0.05), serum bone formation marker level (p < 0.05) and expression of osteogenic gene markers exposure to the 5 and 50 mg Cd/kg diets. However, it had no impact on these indicators under the 1 mg Cd/kg diets, with the exception of expression of osteogenic marker genes. Ca supplementation significantly decreased serum Klotho level (p < 0.05), and fibroblast growth factor 23/Klotho-associated gene expression in the kidney and bone showed significant changes. In conclusion, Ca supplementation has a positive effect on bone formation and bone quality against the damaging impact of Cd, especially with exposure to the 5 mg and 50 mg Cd/kg diet, which may be related to its impact on the fibroblast growth factor 23/Klotho axis.

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Ovarian steroid regulation of angiotensin II-induced water intake in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.1.r90 ◽

1999 ◽

Vol 276 (1) ◽

pp. R90-R96 ◽

Cited By ~ 7

Author(s):

Lori R. Kisley ◽

Randall R. Sakai ◽

Li Yun Ma ◽

Steven J. Fluharty

Keyword(s):

Water Intake ◽

Peptide Hormone ◽

Estradiol Benzoate ◽

Female Rats ◽

Female Rat ◽

Ang Ii ◽

Concurrent Administration ◽

Ovarian Steroid ◽

Steroid Administration ◽

Dose Dependent

Spontaneous water intake as well as thirst elicited by ANG II has been shown to be influenced by the stage of the estrous cycle in the female rat. In these experiments, the contribution of each of the ovarian steroid hormones to the regulation of water intake was examined. Ovariectomized female rats were given replacement doses of estrogen, progesterone, or both, and their responsiveness to an intracerebroventricular injection of ANG II was tested. Forty-eight-hour treatment with estradiol benzoate attenuated ANG II-induced thirst by as much as 70% compared with control animals. The effect of estrogen on drinking was dose dependent and could be completely blocked with concurrent administration of the antiestrogen CI-628. In contrast, progesterone, given alone or after estrogen, did not significantly affect ANG II-induced water intake when animals were tested at 4 or 24 h after steroid administration. A central interaction between the peptide hormone ANG II and estrogen, involving a genomic mechanism, may underlie the cyclicity in water intake behavior observed in the rat.

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Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00476.2003 ◽

2003 ◽

Vol 95 (6) ◽

pp. 2614-2623 ◽

Cited By ~ 37

Author(s):

A. G. Zabka ◽

G. S. Mitchell ◽

E. B. Olson ◽

M. Behan

Keyword(s):

Intermittent Hypoxia ◽

Young Female ◽

Time Dependent ◽

Female Rats ◽

Chronic Intermittent Hypoxia ◽

Middle Aged ◽

Short Term ◽

Hypoxic Response ◽

Long Term Facilitation

Age and the estrus cycle affect time-dependent respiratory responses to episodic hypoxia in female rats. Respiratory long-term facilitation (LTF) is enhanced in middle-aged vs. young female rats ( 72 ). We tested the hypothesis that phrenic and hypoglossal (XII) LTF are diminished in acyclic geriatric rats when fluctuating sex hormone levels no longer establish conditions that enhance LTF. Chronic intermittent hypoxia (CIH) enhances LTF ( 41 ); thus we further predicted that CIH would restore LTF in geriatric female rats. LTF was measured in young (3-4 mo) and geriatric (20-22 mo) female Sasco Sprague-Dawley rats and in a group of geriatric rats exposed to 1 wk of nocturnal CIH (11 vs. 21% O2 at 5-min intervals, 12 h/night). In anesthetized, paralyzed, vagotomized, and ventilated rats, time-dependent hypoxic phrenic and XII responses were assessed. The short-term hypoxic response was measured during the first of three 5-min episodes of isocapnic hypoxia (arterial Po2 35-45 Torr). LTF was assessed 15, 30, and 60 min postepisodic hypoxia. Phrenic and XII short-term hypoxic response was not different among groups, regardless of CIH treatment ( P > 0.05). LTF in geriatric female rats was smaller than previously reported for middle-aged rats but comparable to that in young female rats. CIH augmented phrenic and XII LTF to levels similar to those of middle-aged female rats without CIH ( P < 0.05). The magnitude of phrenic and XII LTF in all groups was inversely related to the ratio of progesterone to estradiol serum levels ( P < 0.05). Thus CIH and sex hormones influence the magnitude of LTF in geriatric female rats.

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