human
***task***
the task is to summarize an input biomedical literature in six sentences

***input***
the input is a biomedical literature

***output***
the output is the summary of an input biomedical literature in six sentences

***documentation***

***examples***

input: polycystic ovary syndrome ( pcos ) characterized by menstrual disturbances and clinical and biochemical manifestations of hyperandrogenism , is the most common gynecological endocrinopathy in women of reproductive age . familial clustering and studies on the prevalence of syndrome in twins suggest an interaction of genetic and environmental factors in the pathogenesis of pcos ( 1 , 2 ) . emerging research findings from animals mentioned fetal androgen excess as a main environmental factor , which could be the origin of the syndrome ( 3 ) . experimental induction of androgen excess during prenatal life in female rhesus monkeys , ewes , and rats has been shown to exert appropriate pcos - like phenotypes ( 4 - 6 ) . among these , rodent models which display reproductive and metabolic disturbances associated with the syndrome , are most cost - effective ones to study ovarian dysfunction and pcos ( 7 , 8 ) . fetal exposure to androgen excess could promote changes in gene expression in differentiating tissues , leading to development of pcos during adulthood ( 9 - 11 ) . over the past decade many candidate genes from pathways assumed to be involved in the etiology of pcos , have been investigated , but none of them were found to play a crucial role in pcos pathogenesis and the genetic pathway of the syndrome has remained unknown ( 12 ) . based on pathophysiologic mechanisms , candidate genes can be categorized as follows : those involved in androgen biosynthesis and metabolism , those involved in insulin resistance , those encoding inflammatory cytokines and those involved in folliculogenesis . among those markers involved in folliculogenesis , antimullerian hormone ( amh ) it has been shown that women with pcos have two to three fold higher amh levels compared to their normal counterparts ( 13 ) . however , data revealed controversial results on amh concentration and gene expression in pcos animal models . in prenatally androgenized sheep findingswere similar to pcos women and amh expression showed reduction in granulosa cells of preantral follicles and increase in antral follicles compared to age - matched adult controls ( 14 ) . wistar rats androgenization , whether pre - or post - natal led to fewer amh - positive follicles in ovaries of adult females ( 15 ) . the aim of the current study was to examine amh and its receptor gene expression in ovaries in rats with prenatally testosterone induced pcos compared to the control group . our study was the first one to investigate amh ( and its receptor ) gene expression in newborn , 10 - day old and adult rats . animals and treatments : all used procedures were approved by the local ethics committee of research institute for endocrine sciences ( ries ) of shahid beheshti university of medical sciences ( tehran , iran ) . adult female wistar rats ( n = 12 , body weight 170 - 190 grams ) were supplied by the animal center of the ries . each virgin female rat was housed in a separate polypropylene cage ( 43 cm 30 cm 15 cm ) with a fertile male of the same strain ( 1 female with 1 male ) for 48 hours in an environmentally controlled room ( temperature 223c , relative humidity 246 % with 12 - h light / dark cycles , light period beginning at 07:00 a.m ) . twelve pregnant rats were randomly divided into experimental and control groups ( n = 6 each ) . presence of a vaginal plug was designated as the first day of pregnancy . on the 20th day of pregnancy , pregnant rats in the experimental group were treated with subcutaneous injection of 5 mg free testosterone ( t - 1500 ; sigma , germany ) dissolved in 500 ml sesame oil and benzyl benzoate ( b6630 , sigma , germany ) , while the control group received only 500 ml of solvent ( sesame oil and benzyl benzoate ) . time and dosage of treatment were determined based on previous published data ( 16 - 18 ) . female pups of each mother were randomly divided into three groups and killed at three stages of life ( day 0 ( newborn ) , 10 - day old and day 75 - 85 ( adult ) ) . hormonal and histological changes of adult offspring confirmed pcos by exhibition of hyperandrogenemia , ovarian cysts and reduction of ovulation . details of these manifestations in experimental group compared to their controls were described previously by ramezani tehrani et al . they reported that testosterone and lh levels , lh / fsh ratio and the number of preantral and antral follicles in ovaries were increased in prenatally androgenized adult female offspring . in contrast , the number of preovulatory follicles and corpora lutea were decreased in these animals . blood and tissue collection and hormones assay : at the time of killing , collected blood samples were centrifuged for five minutes ( 3000 g at 4c ) and plasma was stored at -80 c for further measurements . plasma amh and testosterone levels were measured using rat amh and testosterone elisa kit ( cusabio biotech co , ltd , japan ) . assay sensitivity was 0.6 ng / ml for amh and 0.06 ng / ml for testosterone . rna extraction and real - time quantitative pcr : total rna was extracted from ovarian tissues using the rneasy kit ( qiagen , germany ) . rna quantity and purity were measured using the nanodrop 1000 ( thermo scientific , waltham , and mass ) . amh and amhr2 gene expression were quantitatively assessed by taqman real - time polymerase chain reaction ( qrt - pcr ) . the reactions were performed in 25 l volumes containing 12.5 l probe - pcr master mix ( qiagen , germany ) , 0.25 l rt - mix , 0.8 l forward primer , 0.8 l reverse primer , 0.6 l probe , 8.05 l rnase - free water , and 2 l of the total rna . pcr was performed using the rotor - gene 6000 real - time pcr machine ( corbett research , sydney , australia ) with initial denaturation ( 5 minutes at 95c ) and then a one - step amplification program ( 5 minutes at 95c followed by 45 seconds at 60c ) was repeated 40 times . the relative amount of mrna in each sample was calculated based on its threshold cycle ( ct ) compared to the ct of the housekeeping gene ( - actin ) . relative expression in samples from treated animals and the controls was compared by relative expression analysis using the 2ct method as follows : 2 ( 19 ) . statistical analysis was performed using spss 15.0 software ( chicago , il , usa ) . the means of experimental and controls were compared using a two - tailed unpaired sample t - test . one - way analysis of variance ( anova ) was used to test differences of means between the groups . quantitative rt - pcr results were assessed using rest 2009 software ( qiagen , hilden , germany ) . statistical analysis was performed using spss 15.0 software ( chicago , il , usa ) . the means of experimental and controls were compared using a two - tailed unpaired sample t - test . one - way analysis of variance ( anova ) was used to test differences of means between the groups . quantitative rt - pcr results were assessed using rest 2009 software ( qiagen , hilden , germany ) . female pups of each mother ( 43 experimental and 34 controls ) were randomly divided into three groups as newborn ( n = 26 ) , 10 - day old ( n = 19 ) and adult ( n = 32 ) . measurement of hormones was performed in all female offspring , while gene expression was only evaluated in offspring of those mothers which had female offspring in all age groups ( newborn ( n = 10 ) , 10 - day old ( n = 10 ) and adult ( n = 12 ) ) . plasma total amh levels : hormone levels of amh and testosterone are shown in table 2 . the experimental group had lower , but not significant amh levels in newborns , 10 - day - olds and adults compared to controls ; however , mean testosterone hormone levels in the experimental group were higher than controls in these three groups . a decrease in amh concentrationwas observed in 10 day - olds compared to newborns in both the case and control groups . furthermore , amh level was higher in adults , compared to the 10 day - old and newborns in each group ( p 0.001 ) . compared to the controls , testosterone level was increased , not significantly , in all the three age groups ( p 0.05 ) ; however , a significant positive trend was found from 10 day - olds to adults in cases and controls within the groups ( p 0.001 ) . amh and amhr mrna expression level in ovary : compared to the control group , a relative non - significant decrease was observed for amh gene expression in all three experimental age groups ( newborns 0.806 , 10 day - olds 0.443 , and adults 0.809 fold ) ( figure 1 ) . moreover , amhr mrna relative expression was higher in newborns and adults and lower in 10 - day old experimental group ( 1.432 , 1.057 and 0.263 fold , respectively ) , with none of the differences were statistically significant . in this study , we aimed to examine variation of amh and its receptor gene expression in rats with intrauterine exposure to testosterone excess and exhibited pcos manifestations during adulthood . our results demonstrated that contrary to pcos in women , intrauterine exposure to testosterone excess , reduced biosynthesis and circulating amh concentrations in rats . our data furthermore confirmed that amh receptor expression and testosterone levels were higher in rat pcos models than controls . the pathogenesis of pcos is not clear ; however , growing evidence reveals a strong interaction of genetic components and environmental factors in disease development . one of the indices in pcos women is elevated amh level , which represents an increase in the number of growing follicles and associated with severity of the disease ( 20 ) . however , animal studies on pcos and amh had different results ; for instance , in ewes treated with androgens before birth , amh production was increased by antral follicles in adult animals ( 14 ) ; in contrast pre - and postnatally androgenized wistar rats had fewer numbers of follicles that produced amh , and also greater numbers of follicles , which had been recruited and subsequently undergone atresia compared to controls . furthermore , the number of aromatase - positive antral follicles was greater in these postnatal treated rats compared to controls ( 15 ) . similar results of other studies reported in wistar rats demonstrated a decreased amh expression in experimental group , which could be due to decreased proliferation of granulosa cells in response to prenatal exposure to increased amounts of testosterone . amh serum concentrations observed in our study were appropriate based on the results of its gene expression . in the present study , we observed a non - significant increase in serum testosterone levels in the experimental group . however , the difference between 10 - day - old and adult rats of the both groups was significant . in agreement with the present study , there were no significant differences for serum testosterone levels in adulthood in sprague - dawley rats that received testosterone daily on embryonic days 16 - 19 compared to the controls ( 6 ) . however wang et al . treated pregnant rats with epiandrosterone sulfoconjugate ( dheas ) and found a significant difference in serum testosterone levels in female offspring of the experimental group ( 21 ) . these controversial observations could be partly explained by lack of measurement of free testosterone , which is physiologically active and mediates the biological action of hormone in the target tissues of both genders ( 22 ) . the major limitation of our study was its small sample size , which limited our power to assess the differences . however , to the best of our knowledge , this was the first study investigating amh and its receptor gene expression in rats with prenatally testosterone - induced pcos . furthermore , for the first time we examined amh and amhr gene expression in immature rats . in conclusion , amh receptor expression was higher in rats prenatally exposed to androgen , but serum concentration of amh was decreased in these rats , contrary to those observed in pcos women . further researches with greater sample size and measurement of bioactive forms of hormones are recommended to confirm the findings of this study .
output:

agent
background : anti - mullerian hormone ( amh ) levels reflect the number of small antral follicles in ovaries and expression changes of amh and its receptor are suspected to be involved in the pathogenesis of polycystic ovary syndrome ( pcos ) . objectives : the aim of this study was to evaluate gene expression of amh and its receptor in immature and adult rats prenatally exposed to androgen excess.materials and methods : six pregnant wistar rats in the experimental group were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy , while controls ( n = 6 ) received only 500 ml of solvent . female pups of each mother were randomly divided into three groups as day 0 ( newborn ) , 10 - day old and days 75 - 85 ( adult ) . rnas were extracted from ovarian tissues and relative expression levels for amh and its receptor genes were measured using taqman real - time pcr . serum amh and testosterone levels were measured using elisa method.results : relative amh expression decreased in newborns , 10 - day olds and adults ( 0.806 , 0.443 and 0.809 fold , respectively ) . amhr expression was higher in newborns and adults ( 1.432 and 1.057 fold , respectively ) , while it decreased by 0.263 fold in 10 - day olds , although none of them were significant ( p > 0.05 ) . in addition , amh levels were consistent with the results of gene expression . testosterone hormone levels from 10 day - olds to adults were significantly increased in both study groups ( p = 0.016 ) . conclusions : while amh receptor expression was higher in experimental rats , their serum concentrations of amh were decreased . further researches with greater sample sizes and measurement of bioactive forms of hormones are recommended to confirm the findings of this study .
***task***
the task is to summarize an input biomedical literature in six sentences

***input***
the input is a biomedical literature

***output***
the output is the summary of an input biomedical literature in six sentences

***documentation***

***examples***

input: polycystic ovary syndrome ( pcos ) characterized by menstrual disturbances and clinical and biochemical manifestations of hyperandrogenism , is the most common gynecological endocrinopathy in women of reproductive age . familial clustering and studies on the prevalence of syndrome in twins suggest an interaction of genetic and environmental factors in the pathogenesis of pcos ( 1 , 2 ) . emerging research findings from animals mentioned fetal androgen excess as a main environmental factor , which could be the origin of the syndrome ( 3 ) . experimental induction of androgen excess during prenatal life in female rhesus monkeys , ewes , and rats has been shown to exert appropriate pcos - like phenotypes ( 4 - 6 ) . among these , rodent models which display reproductive and metabolic disturbances associated with the syndrome , are most cost - effective ones to study ovarian dysfunction and pcos ( 7 , 8 ) . fetal exposure to androgen excess could promote changes in gene expression in differentiating tissues , leading to development of pcos during adulthood ( 9 - 11 ) . over the past decade many candidate genes from pathways assumed to be involved in the etiology of pcos , have been investigated , but none of them were found to play a crucial role in pcos pathogenesis and the genetic pathway of the syndrome has remained unknown ( 12 ) . based on pathophysiologic mechanisms , candidate genes can be categorized as follows : those involved in androgen biosynthesis and metabolism , those involved in insulin resistance , those encoding inflammatory cytokines and those involved in folliculogenesis . among those markers involved in folliculogenesis , antimullerian hormone ( amh ) it has been shown that women with pcos have two to three fold higher amh levels compared to their normal counterparts ( 13 ) . however , data revealed controversial results on amh concentration and gene expression in pcos animal models . in prenatally androgenized sheep findingswere similar to pcos women and amh expression showed reduction in granulosa cells of preantral follicles and increase in antral follicles compared to age - matched adult controls ( 14 ) . wistar rats androgenization , whether pre - or post - natal led to fewer amh - positive follicles in ovaries of adult females ( 15 ) . the aim of the current study was to examine amh and its receptor gene expression in ovaries in rats with prenatally testosterone induced pcos compared to the control group . our study was the first one to investigate amh ( and its receptor ) gene expression in newborn , 10 - day old and adult rats . animals and treatments : all used procedures were approved by the local ethics committee of research institute for endocrine sciences ( ries ) of shahid beheshti university of medical sciences ( tehran , iran ) . adult female wistar rats ( n = 12 , body weight 170 - 190 grams ) were supplied by the animal center of the ries . each virgin female rat was housed in a separate polypropylene cage ( 43 cm 30 cm 15 cm ) with a fertile male of the same strain ( 1 female with 1 male ) for 48 hours in an environmentally controlled room ( temperature 223c , relative humidity 246 % with 12 - h light / dark cycles , light period beginning at 07:00 a.m ) . twelve pregnant rats were randomly divided into experimental and control groups ( n = 6 each ) . presence of a vaginal plug was designated as the first day of pregnancy . on the 20th day of pregnancy , pregnant rats in the experimental group were treated with subcutaneous injection of 5 mg free testosterone ( t - 1500 ; sigma , germany ) dissolved in 500 ml sesame oil and benzyl benzoate ( b6630 , sigma , germany ) , while the control group received only 500 ml of solvent ( sesame oil and benzyl benzoate ) . time and dosage of treatment were determined based on previous published data ( 16 - 18 ) . female pups of each mother were randomly divided into three groups and killed at three stages of life ( day 0 ( newborn ) , 10 - day old and day 75 - 85 ( adult ) ) . hormonal and histological changes of adult offspring confirmed pcos by exhibition of hyperandrogenemia , ovarian cysts and reduction of ovulation . details of these manifestations in experimental group compared to their controls were described previously by ramezani tehrani et al . they reported that testosterone and lh levels , lh / fsh ratio and the number of preantral and antral follicles in ovaries were increased in prenatally androgenized adult female offspring . in contrast , the number of preovulatory follicles and corpora lutea were decreased in these animals . blood and tissue collection and hormones assay : at the time of killing , collected blood samples were centrifuged for five minutes ( 3000 g at 4c ) and plasma was stored at -80 c for further measurements . plasma amh and testosterone levels were measured using rat amh and testosterone elisa kit ( cusabio biotech co , ltd , japan ) . assay sensitivity was 0.6 ng / ml for amh and 0.06 ng / ml for testosterone . rna extraction and real - time quantitative pcr : total rna was extracted from ovarian tissues using the rneasy kit ( qiagen , germany ) . rna quantity and purity were measured using the nanodrop 1000 ( thermo scientific , waltham , and mass ) . amh and amhr2 gene expression were quantitatively assessed by taqman real - time polymerase chain reaction ( qrt - pcr ) . the reactions were performed in 25 l volumes containing 12.5 l probe - pcr master mix ( qiagen , germany ) , 0.25 l rt - mix , 0.8 l forward primer , 0.8 l reverse primer , 0.6 l probe , 8.05 l rnase - free water , and 2 l of the total rna . pcr was performed using the rotor - gene 6000 real - time pcr machine ( corbett research , sydney , australia ) with initial denaturation ( 5 minutes at 95c ) and then a one - step amplification program ( 5 minutes at 95c followed by 45 seconds at 60c ) was repeated 40 times . the relative amount of mrna in each sample was calculated based on its threshold cycle ( ct ) compared to the ct of the housekeeping gene ( - actin ) . relative expression in samples from treated animals and the controls was compared by relative expression analysis using the 2ct method as follows : 2 ( 19 ) . statistical analysis was performed using spss 15.0 software ( chicago , il , usa ) . the means of experimental and controls were compared using a two - tailed unpaired sample t - test . one - way analysis of variance ( anova ) was used to test differences of means between the groups . quantitative rt - pcr results were assessed using rest 2009 software ( qiagen , hilden , germany ) . statistical analysis was performed using spss 15.0 software ( chicago , il , usa ) . the means of experimental and controls were compared using a two - tailed unpaired sample t - test . one - way analysis of variance ( anova ) was used to test differences of means between the groups . quantitative rt - pcr results were assessed using rest 2009 software ( qiagen , hilden , germany ) . female pups of each mother ( 43 experimental and 34 controls ) were randomly divided into three groups as newborn ( n = 26 ) , 10 - day old ( n = 19 ) and adult ( n = 32 ) . measurement of hormones was performed in all female offspring , while gene expression was only evaluated in offspring of those mothers which had female offspring in all age groups ( newborn ( n = 10 ) , 10 - day old ( n = 10 ) and adult ( n = 12 ) ) . plasma total amh levels : hormone levels of amh and testosterone are shown in table 2 . the experimental group had lower , but not significant amh levels in newborns , 10 - day - olds and adults compared to controls ; however , mean testosterone hormone levels in the experimental group were higher than controls in these three groups . a decrease in amh concentrationwas observed in 10 day - olds compared to newborns in both the case and control groups . furthermore , amh level was higher in adults , compared to the 10 day - old and newborns in each group ( p 0.001 ) . compared to the controls , testosterone level was increased , not significantly , in all the three age groups ( p 0.05 ) ; however , a significant positive trend was found from 10 day - olds to adults in cases and controls within the groups ( p 0.001 ) . amh and amhr mrna expression level in ovary : compared to the control group , a relative non - significant decrease was observed for amh gene expression in all three experimental age groups ( newborns 0.806 , 10 day - olds 0.443 , and adults 0.809 fold ) ( figure 1 ) . moreover , amhr mrna relative expression was higher in newborns and adults and lower in 10 - day old experimental group ( 1.432 , 1.057 and 0.263 fold , respectively ) , with none of the differences were statistically significant . in this study , we aimed to examine variation of amh and its receptor gene expression in rats with intrauterine exposure to testosterone excess and exhibited pcos manifestations during adulthood . our results demonstrated that contrary to pcos in women , intrauterine exposure to testosterone excess , reduced biosynthesis and circulating amh concentrations in rats . our data furthermore confirmed that amh receptor expression and testosterone levels were higher in rat pcos models than controls . the pathogenesis of pcos is not clear ; however , growing evidence reveals a strong interaction of genetic components and environmental factors in disease development . one of the indices in pcos women is elevated amh level , which represents an increase in the number of growing follicles and associated with severity of the disease ( 20 ) . however , animal studies on pcos and amh had different results ; for instance , in ewes treated with androgens before birth , amh production was increased by antral follicles in adult animals ( 14 ) ; in contrast pre - and postnatally androgenized wistar rats had fewer numbers of follicles that produced amh , and also greater numbers of follicles , which had been recruited and subsequently undergone atresia compared to controls . furthermore , the number of aromatase - positive antral follicles was greater in these postnatal treated rats compared to controls ( 15 ) . similar results of other studies reported in wistar rats demonstrated a decreased amh expression in experimental group , which could be due to decreased proliferation of granulosa cells in response to prenatal exposure to increased amounts of testosterone . amh serum concentrations observed in our study were appropriate based on the results of its gene expression . in the present study , we observed a non - significant increase in serum testosterone levels in the experimental group . however , the difference between 10 - day - old and adult rats of the both groups was significant . in agreement with the present study , there were no significant differences for serum testosterone levels in adulthood in sprague - dawley rats that received testosterone daily on embryonic days 16 - 19 compared to the controls ( 6 ) . however wang et al . treated pregnant rats with epiandrosterone sulfoconjugate ( dheas ) and found a significant difference in serum testosterone levels in female offspring of the experimental group ( 21 ) . these controversial observations could be partly explained by lack of measurement of free testosterone , which is physiologically active and mediates the biological action of hormone in the target tissues of both genders ( 22 ) . the major limitation of our study was its small sample size , which limited our power to assess the differences . however , to the best of our knowledge , this was the first study investigating amh and its receptor gene expression in rats with prenatally testosterone - induced pcos . furthermore , for the first time we examined amh and amhr gene expression in immature rats . in conclusion , amh receptor expression was higher in rats prenatally exposed to androgen , but serum concentration of amh was decreased in these rats , contrary to those observed in pcos women . further researches with greater sample size and measurement of bioactive forms of hormones are recommended to confirm the findings of this study .
output:
