EFFECTS OF •1–24 SYNTHETIC CORTICOTROPHIN ON REPRODUCTIVE TRACT AND KIDNEYS OF IMMATURE FEMALE MICE

1967 ◽  
Vol 55 (1) ◽  
pp. 62-70 ◽  
Author(s):  
John J. Christian

ABSTRACT Four units of synthetic β1–24 corticotrophin (Ciba) were given daily to 12 sham-adrenalectomized (»intact«) and to 12 adrenalectomized female mice beginning at 33–39 days of age. Adrenalectomy was at 24–30 days of age and daily injections of 50 μg of cortisol acetate were begun at once. Synthetic corticotrophin (ACTH), like porcine ACTH, inhibited reproductive function in intact and adrenalectomized mice. One intact mouse had degenerate corpora lutea, but the other intact mice had none. There were no ripe follicles and uteri were anoestrous and usually mucified. Effects of synthetic ACTH in adrenalectomized mice were similar but less marked. This ACTH resulted in glomerular lesions similar to those produced by highly purified porcine ACTH at a roughly comparable dose (4 IU). Lesions were marked by an increase in intercapillary weakly PAS+, fibrillar-appearing material, increased size and cellularity of tuft, reduction in number and peripheralization of patent glomerular capillaries, and occasional deposits of brightly PAS positive material in the tufts, juxtaglomerular regions, and at bases of epithelial cells of distal tubules in proximity to glomeruli. Since β1–24 ACTH is very weakly antigenic compared to β1–24 or natural ACTH, it is unlikely that the production of renal lesions and inhibition of reproductive function result from an immune response and therefore is probably an inherent extra-adrenal action of the β1–24 ACTH core. Other pertinent effects of the synthetic ACTH are given.

1993 ◽  
Vol 7 (6) ◽  
pp. 599-606 ◽  
Author(s):  
Laura M. Walters ◽  
Arthur W. Rourke ◽  
Victor P. Eroschenko

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1879-1885 ◽  
Author(s):  
Christine K. Ratajczak ◽  
Katie L. Boehle ◽  
Louis J. Muglia

Evidence in humans and rodents suggests that normal circadian rhythmicity is important for supporting reproductive function. A molecular clock underlies circadian rhythmicity. Impaired fertility is observed in some genetically altered mice with deficiencies in genes of the molecular clock, suggesting a critical role for these genes in reproduction. Here we systematically characterize the reproductive phenotype of females deficient in the clock gene Bmal1. Bmal1−/− females are infertile. They exhibit progression through the estrous cycle, although these cycles are prolonged. Normal follicular development occurs in Bmal1−/− females, and healthy embryos of the expected developmental stage are found in the reproductive tract of Bmal1−/− females 3.5 d after mating to wild-type males. However, serum progesterone levels are significantly lower in Bmal1−/−vs. Bmal1+/± females on d 3.5 of gestation. Low progesterone levels in Bmal1−/− females are accompanied by decreased expression of steroidogenic acute regulatory protein in corpora lutea of Bmal1−/−vs. Bmal1+/± females. Whereas implantation of embryos is not observed in untreated or vehicle-treated Bmal1−/− females, exogenous administration of progesterone to Bmal1−/− females is able to reinstitute implantation. These data suggest that implantation failure due to impaired steroidogenesis causes infertility of Bmal1−/− females.


2020 ◽  
Vol 176 (1) ◽  
pp. 74-85 ◽  
Author(s):  
Isabela V Sarmento ◽  
Eduardo Merlo ◽  
Silvana S Meyrelles ◽  
Elisardo C Vasquez ◽  
Genoa R Warner ◽  
...  

Abstract Tributyltin (TBT) chloride is an endocrine disrupting chemical associated with reproductive complications. Studies have shown that TBT targets the reproductive tract, impairing ovarian folliculogenesis, and uterine morphophysiology. In this investigation, we assessed whether subchronic and low dose of TBT exposure results in abnormal ovarian follicular reserve and other irregularities in female mice. TBT was administered to female mice (500 ng/kg/day for 12 days via gavage), and reproductive tract morphophysiology was assessed. We further assessed reproductive tract inflammation and oxidative stress. Improper functioning of the reproductive tract in TBT mice was observed. Specifically, irregular estrous cyclicity and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. In addition, improper follicular development and a reduction in antral follicles, corpora lutea, and total healthy ovarian follicles together with an increase in cystic follicles were apparent. Evidence of uterine atrophy, reduction in endometrial gland number, and inflammation and oxidative stress were seen in TBT mice. Further, strong negative correlations were observed between testosterone levels and primordial, primary, and total healthy ovarian follicles. Thus, these data suggest that the subchronic and low dose of TBT exposure impaired ovarian follicular reserve, uterine gland number, and other reproductive features in female mice.


1985 ◽  
Vol 38 (1) ◽  
pp. 115 ◽  
Author(s):  
Victor WK Lee ◽  
William RGibson

Ovarian follicular growth was induced in immature female mice with varying doses of pregnant mare's serum gonadotrophin. The numbers of ovulations were determined either by counting tubal oocytes or corpora lutea in the ovary. Ovarian and circulatory levels of inhibin rose progressively with increasing doses of PMSG and a positive correlation (P < O� 0 I) was found between circulating inhibin levels and ovulation rate. The latter correlation makes it likely that the growing preovulatory ovarian follicles are the predominant source for the secretion of inhibin into the circulatory system.


1979 ◽  
Vol 41 (04) ◽  
pp. 804-810 ◽  
Author(s):  
Knut Nordstoga

SummaryThe composition of the occlusive material within dilated glomerular capillaries, following intravenous injections of Liquoid in blue foxes, was studied electron microscopically; it was found that it mainly consisted of a debris in which disintegrated red cells constituted the major component. Damaged platelets and necrotic endothelial remnants were other components. These observations were interpreted as a result of glomerular stasis, and it was concluded that stasis in glomerular capillaries is a basic event in the development of the renal lesions accompanying the generalized Shwartzman reaction.


1960 ◽  
Vol XXXIV (III) ◽  
pp. 375-389 ◽  
Author(s):  
P. S. Brown

ABSTRACT Selected human urinary gonadotrophins were assayed against one another using various measures of response in the same immature female mice. Intact or hypophysectomized animals were used and in some experiments the results of hypophysectomy were checked in complete serial sections. Extracts from the urine of two subjects with Turner's syndrome were compared. In intact mice, the relative potency judged by the ovarian response differed from that shown by the uterine response and the 95 % fiducial limits of the two estimates did not overlap. When the mice were hypophysectomized, one extract became much less potent while the other did not. Similar differences were shown in the response of intact mice to urinary extracts from two subjects with Klinefelter's syndrome. There was a marked disparity between the relative potencies shown by the uterine response and by the incidence of vaginal opening. Similar differences were not shown between the responses to different extracts from the urine of normal postmenopausal women, but these extracts were known to differ little in quality. The results are interpreted in terms of qualitative differences between human urinary gonadotrophins.


Author(s):  
Choudhuri D. ◽  
Bhattacharjee T.

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.


2004 ◽  
Vol 183 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Mika Suzuki ◽  
Hiroshi Kobayashi ◽  
Yoshiko Tanaka ◽  
Naohiro Kanayama ◽  
Toshihiko Terao

Bikunin, a Kunitz-type protease inhibitor, is found in blood and urine. It has been established by two laboratories independently that the bikunin knockout female mice display a severe reduction in fertility: the cumulus oophorus has a defect in forming the extracellular hyaluronan-rich matrix during expansion. Proteins of the inter-alpha-trypsin inhibitor (ITI) family are eliminated in mice in which the bikunin gene has been inactivated, since bikunin is essential for their biosynthesis. Proteins of the ITI family may contribute to the microenvironment in which ovulation takes place. It is not clear, however, whether a single mechanism affects the reproductive function including ovulation. For identifying the full repertoire of the ITI deficiency-related genes, a cDNA microarray hybridization screening was conducted using mRNA from ovaries of wild-type or bik−/− female mice. A number of genes were identified and their regulation was confirmed by real-time RT-PCR analysis. Our screen identified that 29 (0.7%) and 5 genes (0.1%) of the genes assayed were, respectively, up- and down-regulated twofold or more. The identified genes can be classified into distinct subsets. These include stress-related, apoptosis-related, proteases, signaling molecules, aging-related, cytokines, hyaluronan metabolism and signaling, reactive oxygen species-related, and retinoid metabolism, which have previously been implicated in enhancing follicle development and/or ovulation. Real-time RT-PCR analysis confirmed that these genes were up- and down-regulated two- to tenfold by bikunin knockout. These studies demonstrate that proteins of the ITI family may exert potent regulatory effects on a major physiological reproductive process, ovulation.


2017 ◽  
Vol 29 (7) ◽  
pp. 1426 ◽  
Author(s):  
K. A. Walters ◽  
M. C. Edwards ◽  
M. Jimenez ◽  
D. J. Handelsman ◽  
C. M. Allan

Androgens synergise with FSH in female reproduction but the nature of their interaction in ovarian function and fertility is not clear. In the present study, we investigated this interaction, notably whether higher endogenous FSH can overcome defective androgen actions in androgen receptor (AR)-knockout (ARKO) mice. We generated and investigated the reproductive function of mutant mice exhibiting AR resistance with or without expression of human transgenic FSH (Tg-FSH). On the background of inactivated AR signalling, which alone resulted in irregular oestrous cycles and reduced pups per litter, ovulation rates and antral follicle health, Tg-FSH expression restored follicle health, ovulation rates and litter size to wild-type levels. However, Tg-FSH was only able to partially rectify the abnormal oestrous cycles observed in ARKO females. Hence, elevated endogenous FSH rescued the intraovarian defects, and partially rescued the extraovarian defects due to androgen insensitivity. In addition, the observed increase in litter size in Tg-FSH females was not observed in the presence of AR signalling inactivation. In summary, the findings of the present study reveal that FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility.


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