scholarly journals Evidence for increased tissue androgen sensitivity in neurturin knockout mice

2013 ◽  
Vol 218 (2) ◽  
pp. 151-163 ◽  
Author(s):  
Ulla Simanainen ◽  
Yan Ru (Ellen) Gao ◽  
Reena Desai ◽  
Mark Jimenez ◽  
Jennifer Spaliviero ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Structural Changes ◽  
Reproductive Function ◽  
Reproductive Organs ◽  
Gnrh Analogue ◽  
Accessory Glands ◽  
Serum Lh ◽  
Androgen Sensitivity ◽  
In The Wild ◽  
Circulating Levels

Neurturin (NTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family and signals through GDNF family receptor alpha 2 (GFRα2). We hypothesised that epithelial atrophy reported in the reproductive organs ofNtn(Nrtn)- andGfrα2(Gfra2)-deficient mice could be due to NTN affecting the hormonal environment. To investigate this, we compared the reproductive organs ofNtn- andGfrα2-deficient male mice in parallel with an analysis of their circulating reproductive hormone levels. There were no significant structural changes within the organs of the knockout mice; however, serum and intratesticular testosterone and serum LH levels were very low. To reconcile these observations, we tested androgen sensitivity by creating a dihydrotestosterone (DHT) clamp (castration plus DHT implant) to create fixed circulating levels of androgens, allowing the evaluation of androgen-sensitive endpoints. At the same serum DHT levels, serum LH levels were lower and prostate and seminal vesicle weights were higher in theNtnknockout (NTNKO) mice than in the wild-type mice, suggesting an increased response to androgens in the accessory glands and hypothalamus and pituitary of the NTNKO mice. Testicular and pituitary responsiveness was unaffected in the NTNKO males, as determined by the response to the human chorionic gonadotrophin or GNRH analogue, leuprolide, respectively. In conclusion, our results suggest that NTN inactivation enhances androgen sensitivity in reproductive and neuroendocrine tissues, revealing a novel mechanism to influence reproductive function and the activity of other androgen-dependent tissues.

The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis

2018 ◽  
Vol 106 (4) ◽  
pp. 389-400 ◽  
Author(s):  
Kirsty A. Walters ◽  
Melissa C. Edwards ◽  
Dijana Tesic ◽  
Aimee S.L. Caldwell ◽  
Mark Jimenez ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Mrna Expression ◽  
Knockout Mice ◽  
Ovarian Follicle ◽  
Reproductive Function ◽  
Fold Increase ◽  
Antral Follicle ◽  
Hpg Axis ◽  
Serum Lh

The androgen receptor (AR) is expressed throughout the hypothalamic-pituitary-gonadal (HPG) axis, and findings from female global AR knockout mice confirm that AR-mediated androgen actions play important roles in regulating female reproductive function. We generated neuron-specific AR knockout mice (NeurARKO) to investigate the functional role of neuronal AR-mediated androgen action in regulating the female HPG axis and fertility. Relative to control females, NeurARKO females exhibited elevated luteinizing hormone (LH) levels at diestrus (p < 0.05) and a compromised serum LH response to ovariectomy and E2 priming (p < 0.01). Furthermore, NeurARKO females displayed reduced Kiss1 mRNA expression in the anteroventral periventricular nucleus at diestrus (p < 0.05) and proestrus (p < 0.05), but elevated Kiss1 (p < 0.05) and neurokinin B (Tac2, p < 0.05) mRNA expression in the arcuate nucleus at proestrus compared to WT controls. Ovarian follicle dynamics were also altered in NeurARKO ovaries at 3 months of age, with a significant reduction in large antral follicle numbers at the proestrus stage compared to control WT ovaries (p < 0.05). Increased follicular atresia was evident in NeurARKO ovaries with a 4-fold increase in unhealthy large preantral follicles (p < 0.01). Despite the findings of aberrant neuroendocrine and ovarian characteristics in the NeurARKO females, estrous cyclicity and overall fertility were comparable between NeurARKO and WT females. In conclusion, our findings revealed that selective loss of neuronal AR actions impacts the kisspeptin/GnRH/LH cascade leading to compromised ovarian follicle dynamics.

Morphological features of endo- and myometrium in patients with uterine leiomyoma and infertility

2020 ◽  
pp. 33-37
Author(s):  
M.A. Flaksenberg ◽  
◽  
Keyword(s):  
Uterine Leiomyoma ◽  
Negative Impact ◽  
Reproductive Function ◽  
Cell Types ◽  
Underlying Disease ◽  
Reproductive Organs ◽  
Pathological Process ◽  
Simple Type ◽  
Morphological Examination ◽  
Blastocyst Implantation

The objective: determination of morphofunctional features of leiomatous nodes and endometrium in women with uterine leiomyoma and infertility to restore reproductive function and prevent recurrence of the underlying disease. Materials and methods. In order to restore reproductive function and prevent recurrence of the underlying disease, morphofunctional features of leiomatous nodes and endometrium in women with uterine leiomyoma and infertility were determined. Thirty samples of leiomyomatous nodes and endometrium were examined, among which 15 were obtained from women with multiple uterine leiomyoma and infertility and 15 samples from women with uterine leiomyoma with isolated uterine leiomyoma. During the study, a general-histological method was used for staining with hematoxylin-eosin and picrofuxin by van Gizon, as well as immunohistochemical methods. Histological examination of the endometrium was performed according to conventional protocol, taking into account the day of the menstrual cycle and R.W. Noyes criteria. Results. In the morphological examination of leiomyomatous nodes in the vast majority of cases the presence of uterine leiomyomas of simple and cell types or their combination was established. In women with multiple uterine leiomyoma, simple-type leiomyoma (53.3%) was predominant, and in patients with isolated leiomyoma the signs of cellular uterine leiomyoma (66.7%) were more frequently found. In 80.0% of women with uterine leiomyoma revealed pathology of the endometrium, such as glandular and glandular-fibrous polyps, simple and complex atypical endometrial hyperplasia, which confirms the theory about the only pathogenetic mechanisms of the emergence of hyperplastic processes of female organs. In 66.7% of women with multiple leiomyomas, signs of chronic endometritis have been found, which exacerbates the pathological process and can have a negative impact on the reproductive function, such as secretory endometrial transformation and impaired blastocyst implantation, and explains a much higher percentage of infertility in the group. Conclusion. In women with impaired reproductive function, patients with uterine leiomyoma, it is necessary to conduct a study of the receptivity of the reproductive organs, namely - the endometrium and leiomatous nodes. This will make it possible to use one or another method of treatment in order to restore reproductive function and prevent recurrence of the underlying disease. Keywords: infertility, uterine leiomyoma, endometrium, receptive apparatus.

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

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.

scholarly journals Twice-Daily Subcutaneous Injection of Kisspeptin-54 Does Not Abolish Menstrual Cyclicity in Healthy Female Volunteers

2013 ◽  
Vol 98 (11) ◽  
pp. 4464-4474 ◽  
Author(s):  
C. N. Jayasena ◽  
A. N. Comninos ◽  
G. M. K. Nijher ◽  
A. Abbara ◽  
A. De Silva ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Reproductive Function ◽  
Reproductive Hormones ◽  
Follicular Phase ◽  
Hypothalamic Amenorrhea ◽  
Healthy Women ◽  
Lh Pulsatility ◽  
Serum Lh ◽  
Healthy Female ◽  
Ultrasound Parameters

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P &lt; .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P &lt; .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P &lt; .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

ENDOCRINE STUDIES AND SUCCESSFUL TREATMENT IN A PATIENT WITH TRUE HERMAPHRODITISM

1979 ◽  
Vol 91 (1) ◽  
pp. 184-192
Author(s):  
Evangelina Valdés ◽  
Carlos Fernández del Castillo ◽  
Raul Gutiérrez ◽  
Fernando Larrea ◽  
Martha Medina ◽  
...  
Keyword(s):  
Chromosome Complement ◽  
Reproductive Function ◽  
External Genitalia ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Normal Children ◽  
Serum Lh ◽  
Genital Ambiguity ◽  
And Gender ◽  
Lh Rh

ABSTRACT A 12-year old, 46 XX true hermaphrodite born with genital ambiguity was studied and successfully treated. The serum LH and FSH profile resembled that of a pubertal normal individual, and LH-RH administration induced a normal LH response. Baseline testosterone serum levels were within the range for normal children. Exogenous HCG stimulation induced a significant serum testosterone increase up to values similar to those observed in normal post-pubertal males. Surgical examination disclosed the presence of bilateral ovotestis, normal Mullerian derivatives, epididymis, and vas deferens. A complete ovotestis with testicular predominance and the testicular portion of the contralateral ovotestis as well as the Wolffian derivatives, were removed. A further HCG stimulation 3 months after surgery, failed to induce serum testosterone increase. Spontaneous menarche was observed 6 months after surgery and ovulation was well documented. At present the patient has several characteristics of female sex including those of chromosome complement, gonad, internal and external genitalia, hormone levels and gender identity, thus demonstrating that treatment was successful and that reproductive function could be obtained. The finding of spontaneous ovulation following removal of the testicular portion suggests normal cyclic gonadotrophic release implying a difference between animal models and man in regard to hypothalamic virilization.

Memoirs: On the Development of the Male Genitalia and the Efferent Genital Ducts in Lepidoptera

1933 ◽  
Vol s2-76 (301) ◽  
pp. 35-61
Author(s):  
DEV RAJ MEHTA
Keyword(s):  
Male Genitalia ◽  
Abdominal Segment ◽  
Larval Instar ◽  
Ejaculatory Duct ◽  
External Genitalia ◽  
Reproductive Organs ◽  
Proximal Portion ◽  
Genital System ◽  
Larval Life ◽  
Accessory Glands

A general account of the internal reproductive organs and the external genitalia and their development is given. The ‘penis lobes’ develop earlier than the ‘valvae lobes’, and independently of them. The tegumen is the modified ninth tergite. The tenth segment is visibly distinguished into a tergal and sternal part in the pupal stages, and the anal tube passes between the two sclerites. The uncus and the gnathos are dorsal and ventral processes respectively of the tenth segment. The anellus lobes develop as lateral processes of the ninth sternite on either side of the penis. The vasa deferentia during larval life do not extend beyond the eighth abdominal segment and lie in a latero-ventral position. They meet the extensions from the ectodermal ‘ductus ejaculatorius duplex’ during the last larval stadium. From the earliest caterpillar stage there exists a pair of ectodermal ducts formed by the differentiation of the epidermis on the ninth sternite. Towards the end of larval life they divide by constriction to form the accessory glands and the ‘ductus ejaculatory duplex’. At this stage they extend on either side to meet the vasa deferentia. The vesiculae seminales develop by distension from the region of junction between the vasa deferentia and the proximal portion of the ejaculatory duct. The ‘ductus ejaculatorius simplex’ arises as an ectodermal invagination between the pair of ‘penis lobes’ during the final larval instar. It is established that, with the exception of the vasa deferentia, all the remaining elements in the efferent genital system are derived from the ectoderm.

scholarly journals Assembly of T-Antigen Double Hexamers on the Simian Virus 40 Core Origin Requires Only a Subset of the Available Binding Sites

1998 ◽  
Vol 18 (5) ◽  
pp. 2677-2687 ◽  
Author(s):  
Woo S. Joo ◽  
Henry Y. Kim ◽  
John D. Purviance ◽  
K. R. Sreekumar ◽  
Peter A. Bullock
Keyword(s):  
Structural Changes ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Wild Type ◽  
The Core ◽  
Structural Distortions ◽  
In The Wild ◽  
Sv40 Dna ◽  
Initial Assembly

ABSTRACT Initiation of simian virus 40 (SV40) DNA replication is dependent upon the assembly of two T-antigen (T-ag) hexamers on the SV40 core origin. To further define the oligomerization mechanism, the pentanucleotide requirements for T-ag assembly were investigated. Here, we demonstrate that individual pentanucleotides support hexamer formation, while particular pairs of pentanucleotides suffice for the assembly of T-ag double hexamers. Related studies demonstrate that T-ag double hexamers formed on “active pairs” of pentanucleotides catalyze a set of previously described structural distortions within the core origin. For the four-pentanucleotide-containing wild-type SV40 core origin, footprinting experiments indicate that T-ag double hexamers prefer to bind to pentanucleotides 1 and 3. Collectively, these experiments demonstrate that only two of the four pentanucleotides in the core origin are necessary for T-ag assembly and the induction of structural changes in the core origin. Since all four pentanucleotides in the wild-type origin are necessary for extensive DNA unwinding, we concluded that the second pair of pentanucleotides is required at a step subsequent to the initial assembly process.

scholarly journals Changes in African Elephant (Loxodonta africana) faecal steroid concentrations post-defaecation

Bothalia ◽  
2018 ◽  
Vol 48 (1) ◽  
Author(s):  
Judith T. Webber ◽  
Michelle D. Henley ◽  
Yolanda Pretorius ◽  
Michael J. Somers ◽  
Andre Ganswindt
Keyword(s):  
Reproductive Function ◽  
Loxodonta Africana ◽  
African Elephant ◽  
Sample Collection ◽  
Male And Female ◽  
Freeze Dried ◽  
Metabolite Concentrations ◽  
Endocrine Status ◽  
In The Wild ◽  
Sun And Shade

Background: Faecal hormone metabolite measurement is a widely used tool for monitoring reproductive function and response to stressors in wildlife. Despite many advantages of this technique, the delay between defaecation, sample collection and processing may influence steroid concentrations, as faecal bacterial enzymes can alter steroid composition post-defaecation.Objectives: This study investigated changes in faecal glucocorticoid (fGCM), androgen (fAM) and progestagen (fPM) metabolite concentrations in faeces of a male and female African elephant (Loxodonta africana) post-defaecation and the influence of different faeces-drying regimes.Method: Subsamples of fresh faeces were frozen after being dried in direct sun or shade for 6, 20, 24, 48 and 72 h and 7 and 34 days. A subset of samples for each sex was immediately frozen as controls. Faecal hormone metabolite concentrations were determined using enzyme immunoassays established for fGCM, fAM and fPM monitoring in male and female African elephants.Results: Hormone metabolite concentrations of all three steroid classes were stable at first, but changed distinctively after 20 h post-defaecation, with fGCM concentrations decreasing over time and fPM and fAM concentrations steadily increasing. In freeze-dried faeces fGCM concentrations were significantly higher than respective concentrations in sun-dried material, which were in turn significantly higher than fGCM concentrations in shade-dried material. In contrast, fAM concentrations were significantly higher in sun- and shade-dried faeces compared to freeze-dried faeces. Higher fPM concentrations were also found in air-dried samples compared to lyophilised faeces, but the effect was only significant for sun-dried material.Conclusion: The revealed time restriction for collecting faecal material for hormone monitoring from elephants in the wild should be taken into account to assure reliable and comparable results. However, if logistics allow a timely collection, non-invasive hormone measurement remains a powerful and reliable approach to provide information about an elephant’s endocrine status.

scholarly journals Analysis of menstrual and reproductive function in women with infertility and varicose gonadic veins

2018 ◽  
Vol 22 (4) ◽  
pp. 660-665
Author(s):  
O.V. Astakhova ◽  
O.B. Malinina ◽  
A.M. Grigorenko
Keyword(s):  
Menstrual Cycle ◽  
Functional Properties ◽  
Structural Changes ◽  
Varicose Veins ◽  
Venous Blood ◽  
Reproductive Function ◽  
Uterine Bleeding ◽  
Endocrine Function ◽  
Venous Blood Flow ◽  
Significant Percentage

The problem of reproductive health in Ukraine over the last decade has become very important. The greatest clinical interest is infertility, which is accompanied by a violation of the ovulatory function of the ovaries due to hypothalamic-pituitary-ovarian failure. Sustained anovulation for a long time, as well as the lack of adequate correction of menstrual disorders, lead to the development of endocrine-dependent gynecological diseases, the manifestation of which is primary or secondary infertility. Increased flow of venous blood through the ovarian veins is accompanied by phlebostasis and phlebohypertension in the venous sector of the internal genital organs. Increasing the viscosity and rheological properties of blood that occurs at the same time leads to a deterioration of transcapillary metabolism and transport of oxygen to tissues. In the ischemic ovary, degenerative changes in the follicular apparatus, yellow bodies, followed by spreading to all the ovarian structural elements, which leads to its atrophy and reduced functional properties. Considering the importance of venous blood flow in the development of hormonal imbalance as a result of a violation of the endocrine function of the ovaries, the purpose of our study was to assess the menstrual and reproductive function of infertile women against the background of varicose veins. The reproductive function of women with infertility and varicose changes in ovarian veins is represented by a significant percentage of unauthorized miscarriages (41.9%) in the period of pregnancy after 6 weeks (30.6%). In patients with varicose veins in the ovaries, there was a tendency to increase the duration of infertility compared with patients without varicose dilatation of ovarian veins, which may indirectly indicate more significant functional and structural changes in the reproductive organs. In women, both the primary and the comparator groups are predominantly the late and early menarche, but the rates in groups differ slightly in their direction in women with infertility and varicose veins in the ovaries, although they do not reach statistically significant values. The menstrual function of women in the main group is characterized by a regular menstrual cycle (77.5%), regular duration (43.6%) with excessive blood loss during menstruation (54.8%) and a duration of more than 6 days (50.1%) with acyclic uterine bleeding (37.1%), dysmenorrhea (56.4%) and premenstrual disorders (51.6%), which significantly impairs the quality of life of women. At the same time, the violation of the menstrual cycle in the form of its shortening of 16,1% and acyclic uterine bleeding — 6,5%, was gradually increasing with age and was statistically significant against women from the comparison group. Conclusion in the analysis of clinical characteristics, the more significant percentage of changes in the menstrual cycle, reproductive function in women with functional infertility and varicose veins of the ovary compared with patients with infertility without structural changes in ovarian veins indicates the significant importance of venous hemodynamics in the functional properties of the ovary.

The stem-loop binding protein CDL-1 is required for chromosome condensation, progression of cell death and morphogenesis inCaenorhabditis elegans

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Yuki Kodama ◽  
Joel H. Rothman ◽  
Asako Sugimoto ◽  
Masayuki Yamamoto
Keyword(s):  
Cell Death ◽  
Structural Changes ◽  
Binding Protein ◽  
Core Histone ◽  
Loss Of Function ◽  
Histone Proteins ◽  
Stem Loop ◽  
C Elegans ◽  
Morphological Defects ◽  
In The Wild

Histones play important roles not only in the structural changes of chromatin but also in regulating gene expression. Expression of histones is partly regulated post-transcriptionally by the stem-loop binding protein (SLBP)/hairpin binding protein (HBP). We report the developmental function of CDL-1, the C. elegans homologue of SLBP/HBP. In the C. elegans cdl-1 mutants, cell corpses resulting from programmed cell death appear later and persist much longer than those in the wild type. They also exhibit distinct morphological defects in body elongation and movement of the pharyngeal cells toward the buccal opening. The CDL-1 protein binds to the stem-loop structures in the 3′-UTR of C. elegans core histone mRNAs, and the mutant forms of this protein show reduced binding activities. A decrease in the amount of core histone proteins phenocopied the cdl-1 mutant embryos, suggesting that CDL-1 contributes to the proper expression of core histone proteins. We propose that loss-of-function of cdl-1 causes aberrant chromatin structure, which affects the cell cycle and cell death, as well as transcription of genes essential for morphogenesis.

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