Animal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: a systematic review

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Term Occurence Count Dictionary
testosterone 43 endocrinologydiseasesdrugs
17β-estradiol 1 endocrinologydiseasesdrugs
hyperandrogenism 7 endocrinologydiseases
obesity 1 endocrinologydiseases
ovarian dysfunction 2 endocrinologydiseases
polycystic ovary syndrome 1 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
17β-estradiol 20977 report blood androgen concentrations.Four studies described interventions with estradiol valerate or 17β-estradiol in adult animals, with different treatment periods. Three of the studies used female Wistar rats [[33],
testosterone 1970 estrogenic effect did not observe changes in circulating androgens.In conclusion, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype,
testosterone 7438 PCOS-like reproductive characteristics, namely, follicles with cystic appearance and altered serum testosterone levels. We also performed a hand search of the reference lists of full-text articles. Studies were excluded
testosterone 12907 macaque25Testosterone13–16 monthssexual hormonesovarian morphology=TNo cystsNo CL=antral folliclesT testosterone , E2 estradiol, LH luteinizing hormone, FSH follicle-stimulating hormone, CL corpus luteum, PA prenatal
testosterone 13051 hormone, FSH follicle-stimulating hormone, CL corpus luteum, PA prenatal androgenization, DHT dihydro testosterone , DHEA dehydroepiandrosterone, HFD high-fat diet; ↑: increase; ↓ decrease; = equal; --: not availableFive
testosterone 13625 rat strain for medium- and short-term induction, respectively. Wu et al. (2010) [[10]] administered testosterone during gestation and dihydrotestosterone (DHT) through 70 days after birth and found elevated testosterone
testosterone 13666 induction, respectively. Wu et al. (2010) [[10]] administered testosterone during gestation and dihydro testosterone (DHT) through 70 days after birth and found elevated testosterone levels, but no ovarian changes. Yan
testosterone 13733 testosterone during gestation and dihydrotestosterone (DHT) through 70 days after birth and found elevated testosterone levels, but no ovarian changes. Yan et al. (2013) [[12]] administered DHT during gestation and found
testosterone 14190 findings were reported by Tyndall et al. (2012) [[11]], who administered pre- and postnatal treatment with testosterone propionate for 25–90 days and observed cystic follicles as the only change. Finally, Abbott et al.
testosterone 14331 and observed cystic follicles as the only change. Finally, Abbott et al. (1998) [[25]] administered testosterone propionate for 15–88 days, starting at various gestational ages, and found consistent reproductive
testosterone 14539 reproductive features similar to clinical PCOS in female rhesus macaque offspring, such as increased serum testosterone and LH levels, lower follicle stimulating hormone (FSH) levels, and ovaries containing multiples cystic
testosterone 14897 used female rats [[15]–[18], [26], [27]] and one used female mice [[14]]. While most studies used testosterone or DHT, only two studies administered DHEA to induce ovarian dysfunction [[18], [28]]. Misugi et al.
testosterone 15073 dysfunction [[18], [28]]. Misugi et al. (2006) [[18]] observed both cystic/atretic follicles and high testosterone levels in response to DHEA stimulation. Paixão et al. (2015) used a single equine chorionic gonadotropin
testosterone 15344 in prepubertal rats and added DHEA to generate ovarian dysfunction. These animals presented greater testosterone levels and higher number of, and larger-sized, primary and secondary follicles as compared with the
testosterone 15544 compared with the control group [[28]].Ota et al. (1983) [[17]] also found cystic follicles and elevated testosterone levels after administration of testosterone propionate injections to Wistar rats. Ongaro et al. (2015)
testosterone 15588 (1983) [[17]] also found cystic follicles and elevated testosterone levels after administration of testosterone propionate injections to Wistar rats. Ongaro et al. (2015) [[26]] administered a single dose of testosterone
testosterone 15697 testosterone propionate injections to Wistar rats. Ongaro et al. (2015) [[26]] administered a single dose of testosterone propionate to 5-day-old female Sprague–Dawley rats, and found no differences in testosterone or estradiol
testosterone 15792 dose of testosterone propionate to 5-day-old female Sprague–Dawley rats, and found no differences in testosterone or estradiol levels at 30 and 60 days. Cystic follicles were observed only in 60-day-old animals. Marcondes
testosterone 15965 were observed only in 60-day-old animals. Marcondes et al. (2015) [[27]] administered a single dose of testosterone propionate to 0-to-2-day-old female Wistar rats. Increased testosterone levels, cystic follicles, and
testosterone 16037 administered a single dose of testosterone propionate to 0-to-2-day-old female Wistar rats. Increased testosterone levels, cystic follicles, and absence of corpora lutea were found at 90–94 days of age. Manneras et
testosterone 16245 Manneras et al. (2007) [[16]] administered DHT to the same rat strain and found cystic follicles, but no testosterone changes. Unlike Ota et al. (1983) [[17]], who conducted a long-term intervention, the study by Manneras
testosterone 16848 mice under DHT treatment, Zhai et al. (2012) [[15]] studied female Sprague–Dawley rats receiving testosterone plus a high-fat diet.Two studies described postnatal interventions and observed the offspring at different
testosterone 17208 One study did not find any changes [[20]], whereas the other reported cystic follicles and increased testosterone levels [[19]].The four available studies of adult animals were performed on non-human primates [[21]–[24]].
testosterone 17397 non-human primates [[21]–[24]]. Tang et al. (2012) [[21]] observed cystic follicles and increased testosterone levels after medium-term treatment with testosterone propionate plus hCG injection. The other three
testosterone 17450 [[21]] observed cystic follicles and increased testosterone levels after medium-term treatment with testosterone propionate plus hCG injection. The other three studies used long-term treatment with androgens [[22]–[24]].
testosterone 17642 with androgens [[22]–[24]]. McGee et al. (2014) [[22]] found antral follicles and high levels of testosterone after treatment with testosterone plus a high-fat diet. One study of androstenedione intervention [[24]]
testosterone 17676 McGee et al. (2014) [[22]] found antral follicles and high levels of testosterone after treatment with testosterone plus a high-fat diet. One study of androstenedione intervention [[24]] found increased testosterone
testosterone 17776 testosterone plus a high-fat diet. One study of androstenedione intervention [[24]] found increased testosterone levels and atretic follicles but no cystic or antral follicles. Faiman et al. (1988) [[23]], using testosterone
testosterone 17888 levels and atretic follicles but no cystic or antral follicles. Faiman et al. (1988) [[23]], using testosterone as the intervention, did not observe any changes in hormone levels or ovarian morphology.Animal models
testosterone 20164 rats58E2 pellets 50 daysSexual hormonesGonadotropinOvary morphology= E2 ↑ cystic follicles No CLT testosterone , E2 estradiol, LH luteinizing hormone, FSH follicle-stimulating hormone, CL corpus luteum; ↑: increase;
testosterone 21438 for an animal model of PCOS, such as the presence of cystic and atretic follicles alongside elevated testosterone levels.Hemmings et al. (1983) [[35]] administered a single dose of estradiol valerate, whereas Quandt
testosterone 25045 [[48]]Rat10LetrozoleSexual hormonesGonadotropinOvary morphology↑ T, ↓ E2↑ LH, ↑ FSH↑ cystic folliclesT testosterone , E2 estradiol, LH luteinizing hormone, FSH follicle-stimulating hormone, CL corpus luteum; ↑: increase;
testosterone 25646 sequence of the carboxyl-terminal peptide (CTP) of the hCG β-subunit, which promotes increased LH and testosterone secretion as well as polycystic ovaries. Devin et al. (2007) [[39]] generated a mouse that expresses
testosterone 26022 studied an obese transgenic mouse model with leptin receptor dysfunction, and found increased serum testosterone levels and atretic and cystic follicles.Two studies described interventions in pubertal animals. Kafali
testosterone 26369 at el. (2015) [[47]] exposed the animals to continuous light for 16 weeks. Both studies found high testosterone levels and cystic follicles.Seven studies described different interventions in adult animals. Four used
testosterone 27296 studies demonstrated an increased number of ovarian cysts, but only two [[42]] confirmed an increase in testosterone levels. The other three studies reported unchanged testosterone levels [[44], [45]] or did not measure
testosterone 27360 two [[42]] confirmed an increase in testosterone levels. The other three studies reported unchanged testosterone levels [[44], [45]] or did not measure sex hormone levels [[41]].Park and Choi (2012) [[43]] described
testosterone 28112 abnormalities. Both studies revealed ovarian morphological changes. Park and Choi [[43]] reported increased testosterone levels and cystic follicles, whereas Radavelli-Bagatini et al. (2011) [[46]] demonstrated a high number
testosterone 32220 developmental period in which androgen treatment is started [[11]]. In this sense, either starting testosterone treatment postnatally [[14]–[18]] or administering DHT treatment during the prepubertal period [[19],
testosterone 32777 study of Ota et al. [[17]], in which, after treatment of 5-day-old female rats with a single dose of testosterone propionate, various reproductive characteristics of PCOS – such as cystic follicles, anovulation,
testosterone 33639 neonatal female rats were treated with the endocrine disruptor bisphenol A [[32]], and exhibited high testosterone levels and numerous cystic and atretic follicles later in life. Possibly, acute exposure to estrogen
testosterone 35401 LHβ gene and hCG β-subunit [[37]], thus inducing chronic elevation of LH levels as well as increased testosterone and estrogen levels and cystic follicles.Finally, although genetic rodent models cited in the present
testosterone 36950 was associated with development of cystic follicles, most of the studies were unable to demonstrate testosterone overproduction. While other interventions, mainly transgenic animals, were able to induce hyperandrogenism
testosterone 37113 transgenic animals, were able to induce hyperandrogenism and cystic follicles, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype,
Select Disease Character Offset Disease Term Instance
hyperandrogenism 69 Title: Reproductive Biology and Endocrinology : RB&EAnimal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: a systematic reviewLarissa
hyperandrogenism 490 syndrome (PCOS) is a common endocrine disorder, affecting 9–18% of women in reproductive age that causes hyperandrogenism and infertility due to dysfunctional follicular maturation and anovulation. The etiology of PCOS is
hyperandrogenism 2671 [[1]]. PCOS is characterized by at least two of the three following criteria: clinical or biochemical hyperandrogenism , oligo/anovulation, and polycystic ovaries [[2]]. Clinically, these manifestations are associated with
hyperandrogenism 2885 with reduced fertility, due to dysfunctional follicular maturation and consequent anovulation, and hyperandrogenism , causing acne and hirsutism [[3]]. Both chronic anovulation and androgen excess are linked to disturbed
hyperandrogenism 29271 interventions, specifically focusing on two main reproductive features present in women with PCOS: hyperandrogenism and polycystic ovaries.We included 39 experimental studies which used distinct procedures to induce
hyperandrogenism 36687 included 39 reports of animal models inducing two of the most characteristics features of human PCOS: hyperandrogenism and ovarian morphology changes. These studies used different experimental procedures and model organisms.
hyperandrogenism 37053 testosterone overproduction. While other interventions, mainly transgenic animals, were able to induce hyperandrogenism and cystic follicles, medium- or long-term testosterone administration in the pre- and postnatal periods
obesity 27706 (2011) [[46]] studied a mouse strain known as the New Zealand Obese (NZO), which naturally displays obesity , insulin resistance, and a mild form of diabetes, manifestations similar to those that often occur in
ovarian dysfunction 14963 mice [[14]]. While most studies used testosterone or DHT, only two studies administered DHEA to induce ovarian dysfunction [[18], [28]]. Misugi et al. (2006) [[18]] observed both cystic/atretic follicles and high testosterone
ovarian dysfunction 15291 (eCG) dose to induce initial follicular recruitment in prepubertal rats and added DHEA to generate ovarian dysfunction . These animals presented greater testosterone levels and higher number of, and larger-sized, primary
polycystic ovary syndrome 132 Endocrinology : RB&EAnimal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome : a systematic reviewLarissa PaixãoRamon B. RamosAnita LavardaDebora M. MorshPoli Mara SpritzerPublication

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