Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats

1995 ◽  
Vol 133 (3) ◽  
pp. 375-380 ◽  
Author(s):  
Andrea R Genazzani ◽  
Marco A Palumbo ◽  
Antonio A de Micheroux ◽  
Paolo G Artini ◽  
Mario Criscuolo ◽  
...  

Genazzani AR, Palumbo MA, de Micheroux AA, Artini PG, Criscuolo M, Ficarra G, Guo A-L, Benelli A, Bertolini A, Petraglia E. Purdy RH. Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats. Eur J Endocrinol 1995;133:375–80. ISSN 0804–4643 The present study investigated the effect of allopregnanolone (5α-pregnan-3α-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on highpressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events. AR Genazzani, Institute of Obstetrics and Gynecology, University of Pisa, via Roma 67, 56100 Pisa, Italy

Author(s):  
Oyedeji K.O ◽  
Momoh R.O ◽  
Oderinde Gbenga

This study was designed to investigate the effect of penicillin on reproductive function in female Wistar rats. Fifteen female rats (120 – 160 g) were used for the estrous cycle and histopathological studies. Penicillin (17.14 mg/kg) was administered orally on daily basis for 21 and 50 days respectively for the estrous cycle and histological studies. Estrous cycle was carried out using the technique of Marcondes et al., histologies of the ovaries and uteri were also carried out. Data were analysed using descriptive statistics and student’s t-test at p=0.05. Treatment of rats for 21 days with penicillin (17.14 mg/kg) produced significant (p<0.05) increments in the estrous and metestrous phases as well as a significant (p<0.05) reduction in the proestrous phase of the estrous cycle relative to their respective controls. The histopathological study presented with a moderate endometrial congestion. It can therefore be concluded that penicillin probably has a pro-fertility effect with a moderate deleterious effect on the uteri at histological level in female Wistar rats.


2000 ◽  
Vol 278 (6) ◽  
pp. R1627-R1633 ◽  
Author(s):  
A. A. Ammar ◽  
F. Sederholm ◽  
T. R. Saito ◽  
A. J. W. Scheurink ◽  
A. E. Johnson ◽  
...  

Many studies have indicated that neuropeptide Y (NPY) stimulates and leptin inhibits food intake. In line with this, intracerebroventricular injection of NPY (10 μg) stimulated and leptin (10 μg) inhibited intake of a sucrose solution when female rats were required to obtain the solution from a bottle. However, NPY inhibited and leptin stimulated intake if the solution was infused intraorally. Thus NPY stimulates the responses used to obtain food but inhibits those used to consume food, and leptin has the opposite effects. To test the specificity of these responses the sexual behavior of male rats was examined. NPY-treated males showed minor deficits in sexual behavior but chose to ingest a sucrose solution rather than copulate with a female if offered the choice. By contrast, leptin-treated males ingested little sucrose and displayed an increase in ejaculatory frequency if given the same choice. It is suggested that NPY is not merely an orexigenic peptide, but one that directs attention toward food. Similarly, leptin may not be an anorexic peptide, but one that diverts attention away from food toward alternate stimuli.


Author(s):  
Oyedeji K.O

This study was designed to investigate the effect of artesunate on reproductive function in female Wistar rats. Fifteen female rats (120 – 160 g) were used for the estrous cycle and histopathological studies. Artesunate (1.43 mg/kg) was administered orally on daily basis for 21 and 50 days respectively for the estrous cycle and histological studies. Estrous cycle was carried out using the technique of Marcondes et al., histologies of the ovaries and uteri were also carried out. Data were analysed using descriptive statistics and student’s t-test at p=0.05. Treatment of rats for 21 days with artesunate (1.43 mg/kg) produced significant (p<0.05) increments in the estrous and metestrous phases as well as a significant (p<0.05) reduction in the proestrous phase of the estrous cycle relative to their respective controls. The histopathological study presented with ovarian medullar that is severely congested (hemorrhagic) including expanded lumen of the endometrial glands. It can therefore be concluded that artesunate probably has pro-fertility effect with deleterious effect on the ovaries at histological level in female Wistar rats.


2005 ◽  
Vol 184 (2) ◽  
pp. 435-445 ◽  
Author(s):  
C M Gomes ◽  
C Raineki ◽  
P Ramos de Paula ◽  
G S Severino ◽  
C V V Helena ◽  
...  

Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis.


Behaviour ◽  
1972 ◽  
Vol 41 (3-4) ◽  
pp. 288-297 ◽  
Author(s):  
Donna Fitzroy Hardy

AbstractThe succession of vaginal and behavioral changes was followed throughout the estrous cycle of ten continuously cycling female rats. Interruption of cycles by pregnancy or pseudopregnancy was prevented by the use of the vaginal mask. The behavioral indices were Lordosis Quotient, a measure of sexual responsiveness, and Rejection Quotient, a measure of tolerance by the female of mounting by the male. Before the onset of lordosis, which took place during proestrus, females rejected males on many attempted mounts, although rejection decreased rapidly with rise in frequency of lordosis. Full receptivity was displayed for 6 to 9 hours, but females began to reject the males while still displaying high levels of lordosis. The total period of 19 hours over which lordosis is shown was divided into pre-heat, heat, and post-heat periods.


2019 ◽  
pp. 46-54
Author(s):  
L. M. Malanchuk ◽  
L. O. Krasnyanska ◽  
Z. M. Kuchma ◽  
V. M. Martynuik

The objective of the work was to make a comparative analysis of the result of external genital endometriosis treatment with the use of traditional surgical intervention and hormone therapy together with the use of low-molecular-weight metabolic immune response modifier 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione of sodium salt. Materials and methods: the experimental part of the study was previously conducted on 50 female rats which consisted of studying the influence of the immune response modifier on the course of experimentally induced endometriosis in experimental animals, in particular on changes in the estrous cycle. Injection of the immune response modifier caused retrogression of endometrioid heterotopias and normalization of the estrous cycle in the animals. The comparative analysis of the results of external genital endometriosis treatment in 66 women was conducted on the basis of experimental research. 34 women, apart from surgical intervention and hormone therapy, were injected with the immune response modifier 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione of sodium salt during the post surgical period. Cellular immunity, T- and B-lymphocytes, and equipment and instrumental methods, such as medical ultrasound of the organs of the lower pelvis and laparoscopy, were used to assess the results of treatment. As a result of the treatment with the use of the immune response modifier the indicators of cells immunity changed, pain severity decreased, menstrual function normalized, relapse frequency reduced, and the overall quality of life for patients improved. Socially significant effect of treatment of external genital endometriosis using metabolic immune response modifier is manifested in implementation of reproductive function ‒ elimination of infertility in 50 % of women during the first year of observation.


Author(s):  
Oyedeji K.O ◽  
Nwume B. E ◽  
Zachariah Richard

This study was designed to investigate the effect of methotrexate on reproductive function in female Wistar rats. Eighteen female rats (120 – 160 g) were used for the estrous cycle and histopathological studies. Methotrexate (0.071 mg/kg) was administered orally on daily basis for 21 and 50 days respectively for the estrous cycle and histological studies. Estrous cycle was carried out using the technique of Marcondes et al., histologies of the ovaries and uteri were also carried out. Data were analysed using descriptive statistics and student’s t-test at p=0.05. Treatment of rats for 21 days with methotrexate (0.071 mg/kg) produced significant (p<0.05) reductions in the proestrous and estrous phase of the estrous cycle as well as significant (p<0.05) increments in the metestrous and diestrous phases of the estrous cycle relative to their respective controls. The histopathological study revealed that treatment of rats with methotrexate (0.071 mg/kg) for 50 days presented with ovarian medullary part that is congested and oedematous as well as with multiple foci of hemorrhage within the endometria. It can therefore be concluded that that methotrexate probably has dominant pro-fertility effect, but also probably induced deleterious effects on the ovaries and uteri in female Wistar rats.


Author(s):  
Seliukova N. Yu.

Sexual behaviour is an integral part of reproduction and is considered as a neuroendocrine function of the body. It is the result of sexual differentiation of the brain in the early stages of development of the body and is regulated by steroids of the gonads, which is confirmed by the presence of receptors for these hormones in the centre of sexual behaviour. Any negative factors during pregnancy can cause a lot of harm to the unborn child. To date, it is almost unknown how fetoplacental insufficiency affects the reproductive function of offspring of both sexes from birth to puberty very little. The purpose of this work was to study the effects of fetoplacental insufficiency of mothers of different ages on the sexual behaviour of female offspring. Materials and methods of research. The experiment involved healthy sexually mature female mothers of Wistar rats, young (3 months) and mature (10 months) of reproductive age, with a normal four to five day estrous cycle. 4 groups of 7 pregnant females were formed: 1 group, intact young animals; group 2, intact females of mature reproductive age; group 3, young females with experimental fetoplacental insufficiency; 4 - females with experimental fetoplacental insufficiency of mature reproductive age. Modelling of fetoplacental insufficiency was performed by daily subcutaneous injection to females from the 12th to the 18th day of pregnancy 50% oil solution of carbon tetrachloride at a dose of 2 ml/kg body weight. The sexual behaviour of females was studied according to generally accepted methods. After a study of sexual behaviour at the age of 3 months, female offspring were removed from the experiment. The uterus and ovaries were weighed, and the number of follicles in the ovary was counted. The estrous cycle of females was studied. Serum samples were taken to determine the concentration of the hormones estradiol and testosterone. Conclusions and prospects for further development. Fetoplacental insufficiency in young mothers of reproductive age affects the sexual behaviour of female offspring, reduces the number of lordosis reactions by almost 20% and increasing the receptive indicators of sexual behaviour. Such changes occur against the background of elevated levels of sex hormones while reducing the number of cycling females and the number of follicles in the ovary. Due to the fact that the rupture of the follicle and the release of the egg require sequential activation of the secretion of hypothalamic gonadotropin and luteinizing hormone, and against the background of fetoplacental insufficiency, there may be no preovulatory growth of their levels in the blood due to refractoriness of the ovaries. In the study of sexual behaviour of offspring of females born to mothers of mature reproductive age with fetoplacental insufficiency, a decrease in the number of lordosis reactions by 50% of the intact group and increased receptive behaviour were noted. Also, this group of offspring had a reduced number of cycling females but the number of follicles in the ovaries remained within the intact group. Such reproductive changes occurred against the background of elevated testosterone levels, without changes in estradiol concentrations, which led to the relative androgenization of females. The prospect of further development is to study the effects of fetoplacental insufficiency on the fertility of mature offspring of both sexes born to female rats of different reproductive ages with fetoplacental insufficiency. Key words: fetoplacental insufficiency, reproductive system, sexual behaviour, female offspring.


Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5592-5598 ◽  
Author(s):  
Daniele Della Seta ◽  
Francesca Farabollini ◽  
Francesco Dessì-Fulgheri ◽  
Leonida Fusani

Xenoestrogens are endocrine-disrupting chemicals that mimic the action of endogenous estrogen hormones. Effects of xenoestrogen on aquatic wildlife are well documented, whereas the experimental evidence for impairment of reproductive behavior and physiology in mammals after exposure to xenoestrogens has been debated. The strongest arguments against such studies have been that the route, time course, and intensity of exposure did not simulate environmental exposure and that the chemicals tested have additional nonestrogenic toxic effects, hindering generalization of actual xenoestrogenic effects. Here we show that environmental-like exposure to the pure estrogen 17α-ethinylestradiol during development alters reproductive behavior and physiology in adult female Sprague-Dawley rats. We simulated environmental exposure by giving low doses (0.4 and 0.004 μg/kg·d) of 17α-ethinylestradiol orally to pregnant females from conception to weaning of the pups, which continued to receive the treatment until puberty. We studied the sexual behavior, estrous cycle, and estradiol plasma levels of intact female rats when they reached 3 months of age. Exposure to the higher dose strongly affected female sexual behavior and physiology, with suppression of lordosis and the estrous cycle and enhanced aggression toward males. The lower dose disrupted appetitive components of sexual behavior that influence the rate of copulation. Estradiol plasma levels were not affected by the treatment. Our study revealed that exposure to low oral doses of a pure estrogen during development alters female sexual behavior and physiology. These results suggest potential risks of reproductive failure from xenoestrogen exposure in realistic ecological conditions.


2000 ◽  
Vol 19 (5) ◽  
pp. 284-296 ◽  
Author(s):  
T Nagao ◽  
Y Saito ◽  
K Usumi ◽  
M Nakagomi ◽  
S Yoshimura ◽  
...  

A number of alkylphenolic compounds are used in a variety of commercial products and have been shown in in vitro studies to be weakly estrogenic, but few in vivo data are available addressing this issue in mammals. Human ex-posure to alkylphenols may occur not only from these environmental contaminants but also through contact with manufactured and metabolic breakdown products. The reproductive function of rats treated subcutaneously with nonylphenol (NP, 500 mg/kg/day) or 17Q3-estradiol (E2, 2 mg/kg/day) as a positive control, from postnatal days 1 to 5 was examined after puberty. In addition, masculine sexual behavior, sperm motion, plasma testosterone concentration and histopathological changes in the reproductive organs of the rats were examined. Furthermore, male rats were subjected to an open field test and wheel cage test to evaluate locomotor activity, and the estrous cycle was examined in female rats. All male and female rats exposed neonatally to NP or E2 showed macroscopic and/or microscopic altera-tions of the gonads. Females treated with NP or E2 showed an altered estrous cycle and abnormal reproductive function, while males treated with NP or E2 showed normal reproduc-tion. In males exposed neonatally to NP or E2, no abnorm-alities were observed in locomotor activity, sperm motion or plasma testosterone concentration. The results of this study indicate that early neonatal exposure to NP causes dysfunc-tion of postpubertal reproductive function in female rats, as well as disrupted development of gonads in male and female rats. More detailed studies are warranted to assess the possible risks to human and wildlife reproduction from exposure to NP and other environmental chemicals with estrogenic activity.


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