• Klíčová slova
• gonadotoxicita,
• MeSH
• antitumorózní látky škodlivé účinky   toxicita   MeSH
• hormon uvolňující gonadotropiny agonisté   terapeutické užití   MeSH
• klinická studie jako téma MeSH
• kryoprezervace MeSH
• léčba šetřící orgány MeSH
• lidé MeSH
• nádory * terapie   MeSH
• ovarium účinky léků   MeSH
• těhotenství MeSH
• zachování plodnosti * metody   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

There is increasing evidence that bisphenols BPS and BPF, which are analogues of BPA, have deleterious effects on reproduction even at extremely low doses. Indirect exposure via the maternal route (i.e. across the placenta and/or by breastfeeding) is underestimated, although it can be assumed to be a cause of idiopathic female infertility. Therefore, we hypothesised the deleterious effects of exposure to BPA analogues during breastfeeding on the ovarian and oocyte quality of offspring. A 15-day exposure period of pups was designed, whilst nursing dams (N ≥ 6 per experimental group) were treated via drinking water with a low (0.2 ng/g body weight/day) or moderate (20 ng/g body weight/day) dose of bisphenol, mimicking real exposure in humans. Thereafter, female pups were bred to 60 days and oocytes were collected. Immature oocytes were used in the in-vitro maturation assay; alternatively, in-vivo-matured oocytes were isolated and used for parthenogenetic activation. Both in-vitro- and in-vivo-matured oocytes were subjected to immunostaining of spindle microtubules (α-tubulin) and demethylation of histone H3 on the lysine K27 (H3K27me2) residue. Although very low doses of both BPS and BPF did not affect the quality of ovarian histology, spindle formation and epigenetic signs were affected. Notably, in-vitro-matured oocytes were significantly sensitive to both doses of BPS and BPF. Although no significant differences in spindle-chromatin quality were identified in ovulated and in-vivo-matured oocytes, developmental competence was significantly damaged. Taken together, our mouse model provides evidence that bisphenol analogues represent a risk to human reproduction, possibly leading to idiopathic infertility in women.

• MeSH
• aparát dělícího vřeténka účinky léků   metabolismus   patologie   MeSH
• benzhydrylové sloučeniny metabolismus   toxicita   MeSH
• epigeneze genetická MeSH
• fenoly metabolismus   toxicita   MeSH
• fertilita účinky léků   MeSH
• hodnocení rizik MeSH
• IVM techniky MeSH
• kojená zvířata MeSH
• laktace metabolismus   MeSH
• matka - expozice noxám MeSH
• mléko metabolismus   MeSH
• myši inbrední ICR MeSH
• oocyty účinky léků   metabolismus   patologie   MeSH
• ovariální rezerva účinky léků   MeSH
• ovarium účinky léků   metabolismus   patofyziologie   MeSH
• sulfony metabolismus   toxicita   MeSH
• těhotenství MeSH
• vývojová regulace genové exprese MeSH
• ženská infertilita chemicky indukované   metabolismus   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The involvement of the mTOR system/enzyme sirtuin 1 (SIRT1) intracellular signaling system in the control of ovarian functions and its role in mediating hormonal action on the ovary has been proposed, but this hypothesis should be supported by a demonstrated influence of hormones on mTOR/SIRT1. Therefore, the aim of our in vitro experiments was to examine the effect of the known hormonal regulators of ovarian functions, such as follicle-stimulating hormone (FSH), oxytocin (OT) and insulin-like growth factor I (IGF-I), on mTOR/SIRT1. The accumulation of SIRT1 in porcine ovarian granulosa cells cultured with and without these hormones (at doses of 1, 10 or 100 ng.ml-1) was evaluated using immunocytochemistry. It was observed that the addition of FSH (at 10 ng.ml-1 but not at 1 or 100 ng/ml) and OT (at all tested doses) increased the expression of SIRT1 in ovarian cells. In addition, 100 ng.ml-1, but not at 1 or 10 ng.ml-1, of IGF-I decreased SIRT1 accumulation. Our observations are the first demonstration that hormones can directly regulate the ovarian mTOR/SIRT1 system and that this system could mediate the action of hormonal regulators on the ovary.

• MeSH
• apoptóza účinky léků   MeSH
• folikulární buňky cytologie   účinky léků   metabolismus   MeSH
• folikuly stimulující hormon farmakologie   MeSH
• insulinu podobný růstový faktor I farmakologie   MeSH
• kultivované buňky MeSH
• ovarium cytologie   účinky léků   metabolismus   MeSH
• oxytocin farmakologie   MeSH
• prasata MeSH
• proliferace buněk účinky léků   MeSH
• sirtuin 1 biosyntéza   genetika   metabolismus   MeSH
• uterotonika farmakologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

RESEARCH QUESTION: Is individualization of dosing with follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? DESIGN: A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18-40 years) randomized and treated with follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. RESULTS: Individualized dosing with follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Müllerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus follitropin alfa. CONCLUSION: An individualized follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.

• MeSH
• dospělí MeSH
• fertilizace in vitro MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   terapeutické užití   MeSH
• indukce ovulace * škodlivé účinky   MeSH
• interpretace statistických dat MeSH
• intracytoplazmatické injekce spermie MeSH
• kryoprezervace MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ovariální hyperstimulační syndrom prevence a kontrola   MeSH
• ovarium účinky léků   MeSH
• rekombinantní proteiny aplikace a dávkování   terapeutické užití   MeSH
• riziko MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

The aim of present study was to evaluate the action of green tea and its constituents on rabbit ovarian functions and some non-reproductive indexes. In in vitro experiments, rabbit ovarian fragments were cultured with green tea constituents - epigallocatechin-3-gallate (EGCG), green tea polyphenols (GTPP) and resveratrol (RSV) (at 0, 1, 10 or 100 μg/mL medium). The accumulation of an apoptosis marker - caspase 3 and the release of progesterone (P4) and testosterone (T) were measured. In in vivo experiments, does were fed a standard diet or a diet enriched with green tea powder. The weight gain, mortality, ovarian length and weight, conception and kindling rate, number of liveborn, stillborn, and weaned pups, diameter of ovarian follicles and some blood haematological and biochemical parameters were analysed. Culture of ovarian fragments with EGCG increased accumulation of caspase 3, whilst both GTTP and RSV decreased it. EGCG inhibited both P4 and T output, GTPP stimulated P4 and inhibited T, whilst RSV promoted release of both P4 and T. Feeding with green tea increased ovarian length and diameter of ovarian non-ovulated peri-ovulatory haemorrhagic but not of primary and secondary growing follicles. Furthermore, green tea reduced conception and kindling rate, the number of liveborn and weaned pups, increased female mortality but not their weight gain. It reduced platelet distribution width, but it did not affect other haematological and biochemical indexes. These observations suggest that dietary green tea can reduce rabbit doe's viability, ovarian functions and fecundity, perhaps due to changes in ovarian cell apoptosis, steroid hormones release and blockade of the ovulation of large ovarian follicles. The anti-reproductive action of green tea could be due to its constituent - EGCG with pro-apoptotic and anti-steroid hormone properties.

• MeSH
• apoptóza MeSH
• čaj chemie   MeSH
• fertilita účinky léků   MeSH
• kaspasa 3 metabolismus   MeSH
• katechin analogy a deriváty   izolace a purifikace   farmakologie   MeSH
• králíci * MeSH
• ovarium účinky léků   metabolismus   MeSH
• polyfenoly izolace a purifikace   farmakologie   MeSH
• resveratrol izolace a purifikace   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• králíci * MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Bisphenols belong to the endocrine disruptors, affecting reproduction even in extremely low doses. Bisphenol S (BPS) has become widely used as a substitute for the earlier-used bisphenol A; however, its harmlessness is questionable. The aim of this study was to evaluate the effect of BPS on folliculogenesis and oocyte quality after in vivo exposure to low doses of BPS. Four-week-old ICR females (n = 16 in each experimental group) were exposed to vehicle control (VC), BPS1 (0.001 ng BPS.g/bw/day), BPS2 (0.1 ng.g/bw/day), BPS3 (10 ng.g/bw/day) and BPS4 (100 ng.g/bw/day) for 4 weeks. Ovaries were subjected to stereology and nano liquid chromatography-mass spectrometry (LC/MS). Simultaneously, metaphase II oocytes were obtained after pregnant mare serum gonadotrophin and human chorionic gonadotrophin administration, followed by immunostaining. In particular, mating and two-cell embryo flushing were performed. We observed that BPS decreases the amount of ovarian follicles and BPS2 (0.1 ng.g/bw/day) affects the volume of antral follicles. Accordingly, ovarian proteome is affected after BPS2 treatment. While BPS2 dosing results mainly in cytoskeletal damage in matured oocytes, the effects of BPS3 and BPS4 seem to be due instead to epigenetic alterations in oocytes. Arguably, these changes lead to observed affection of in vivo fertilization rate after BPS3 and BPS4 treatment. BPS significantly affects female reproduction astoundingly in extremely low doses. These findings underline the necessity to assess the risk of ongoing BPS exposure for public health.

• MeSH
• choriogonadotropin farmakologie   MeSH
• endokrinní disruptory aplikace a dávkování   MeSH
• fenoly aplikace a dávkování   MeSH
• fertilizace účinky léků   MeSH
• gonadotropiny koňské farmakologie   MeSH
• imunohistochemie MeSH
• myši inbrední ICR MeSH
• myši MeSH
• oocyty účinky léků   metabolismus   MeSH
• ovariální folikul účinky léků   metabolismus   MeSH
• ovarium účinky léků   metabolismus   MeSH
• proteom účinky léků   MeSH
• rozmnožování účinky léků   MeSH
• sulfony aplikace a dávkování   MeSH
• tandemová hmotnostní spektrometrie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The body condition score (BCS) of cows affects their reproductive efficiency, but the underlying mechanism is unclear. We examined the effect of BCS on the basic ovarian cell functions and their responses to gonadotropic and metabolic hormones. We isolated ovarian cells from cows with a tendency toward emaciation (BCS2) and those with an average body condition (BCS3), and we compared their hormonal release and responses to FSH, leptin, ghrelin, and neuropeptide Y (NPY) added at doses of 0, 1, 10, or 100 ng/mL. Progesterone, testosterone, estradiol, and insulin-like growth factor I (IGF-I) release were evaluated by RIA. No differences were found in progesterone or testosterone release between BCS2 and BCS3 cells; however, ovarian cells from BCS2 cows released more estradiol and IGF-I than cells from BCS3 cows. FSH, ghrelin, and NPY promoted progesterone release in BCS2 cells but had no stimulatory or inhibitory effect on BCS3 cells. In contrast, leptin promoted progesterone release in BCS3 cells and inhibited progesterone release in BCS2 cells. FSH also promoted testosterone release in both BCS2 and BCS3 cells but inhibited progesterone at a low dose in BCS3 cells. Leptin inhibited testosterone release in BCS3 cells but not in BCS2 cells. Estradiol release was promoted by leptin and ghrelin in BCS3 cells; however, it was unaffected by leptin and inhibited by ghrelin in BCS2 cells. IGF-I production was promoted by FSH and inhibited by leptin in both groups. Ghrelin suppressed IGF-I release in BCS2 cells and increased IGF-I release in BCS3 cells. NPY promoted IGF-I release in BCS2 cells but not in BCS3 cells. Our results demonstrate the effects of BCS on ovarian cell estradiol and IGF-I (but not progesterone or testosterone) release, as well as on the responses of ovarian cells to FSH, leptin, ghrelin, and NPY.

• MeSH
• estradiol farmakologie   MeSH
• folikulární buňky účinky léků   sekrece   MeSH
• ghrelin farmakologie   MeSH
• insulinu podobný růstový faktor I farmakologie   MeSH
• kultivované buňky MeSH
• leptin farmakologie   MeSH
• ovarium cytologie   účinky léků   sekrece   MeSH
• pohlavní steroidní hormony farmakologie   MeSH
• primární buněčná kultura MeSH
• progesteron farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• skot * MeSH
• tělesná konstituce fyziologie   MeSH
• testosteron farmakologie   MeSH
• zvířata MeSH
• Check Tag
• skot * MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the present study was to examine the role of nutritional status, the metabolic hormone ghrelin and their interrelationships in the control of chicken hormones involved in the regulation of reproduction. For this purpose, we identified the effect of food deprivation, administration of ghrelin 1-18 and their combination on plasma levels of testosterone (T), estradiol (E), arginine-vasotocin (AVT) and growth hormone (GH) as well as the release of these hormones by isolated and cultured ovarian fragments. It was observed that food deprivation reduces plasma T and E and increases plasma AVT and GH levels. Food restriction also reduced the amount of E produced by isolated ovaries, but it did not affect the ovarian secretion of T and AVT. No ovarian GH secretion was detected. Ghrelin administered to ad libitum fed chickens did not affect plasma T and E levels, but it did increase plasma GH and AVT concentrations. Moreover, it partially prevented the effect of food deprivation on plasma E and AVT levels, but not on T or GH levels. Ghrelin administration to control birds promoted ovarian T, but not E or AVT release and reduced T and no other hormonal outputs in birds subjected to food restriction. Our results (1) confirmed the ovarian origin of the main plasma T and E and the extra-ovarian origin of the main blood AVT and GH; (2) showed that food deprivation-induced suppression of reproduction may be caused by suppression of T and E and the promotion of AVT and GH release; (3) suggest the involvement of ghrelin in control chicken E, AVT and GH output; and (4) indicates that ghrelin can either mimic or modify the effect of the intake of low calories on chicken plasma and ovarian hormones, i.e. it can mediate the effect of metabolic state on hormones involved in the control of reproduction.

• MeSH
• biologické markery krev   MeSH
• energetický metabolismus fyziologie   MeSH
• estradiol krev   MeSH
• ghrelin farmakologie   MeSH
• kur domácí MeSH
• ovarium účinky léků   metabolismus   MeSH
• potravinová deprivace fyziologie   MeSH
• růstový hormon krev   MeSH
• testosteron krev   MeSH
• vasotocin krev   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cíl studie: Prezentovat současné možnosti ovariální stimulace u žen s karcinomem prsu před gonadotoxickou léčbou. Typ studie: Literární přehled s vlastním pozorováním. Název a sídlo pracoviště: Gynekologicko-porodnická klinika Lékařské fakulty Masarykovy Univerzity a FN Brno. Metodika: Literární rešerše, rozbor vlastních zkušeností s komplexní léčbou karcinomu prsu u mladých žen plánujících graviditu, definice stimulačních protokolů a využití metod asistované reprodukce. Výsledky: Důležitou součástí zachování fertility žen před chemoterapií je kontrolovaná ovariální stimulace. Dostupné studie prokázaly efektivitu tohoto postupu bez negativního vlivu na progresi karcinomu prsu. V období od ledna do června 2016 jsme na našem pracovišti provedli ovariální stimulaci a odběr oocytů u tří pacientek s karcinomem prsu před zahájením chemoterapie. Byl použit krátký protokol s agonisty GnRH, recFSH a letrozolem. Bylo získáno 13, 12 a 9 oocytů, zamraženo bylo dvanáct oocytů, osm a šest embryí. V průběhu stimulace hladina estradiolu nepřevýšila 1,6 nmol/l. Závěr: Zdravé ani nádorové buňky v prsu nereagují na gonadotropiny FSH, LH ani na hCG. K buněčné proliferaci dochází u řady buněk s estrogenními receptory po expozici estrogenu v závislosti na dávce. Stimulační protokol s GnRH agonisty a letrozolem je efektivní pro zisk dostatečného počtu gamet a s minimálním zvýšením estradiolu. Literární rešerše neprokázala zvýšení rizika ve smyslu progrese karcinomu prsu v souvislosti s ovariální stimulací. Je nutné respektovat doporučení onkologické komise neprodlužovat čas do zahájení chemoterapie a účinně blokovat vzestup estrogenů při stimulaci.

Objective: To present current options and own experiences with ovarian stimulation in young women with breast cancer before gonadotoxic therapy. Design: Review article with own experiencies. Methods: Literary search, analysis of own experiences with complex therapy in women with breast cancer planning pregnancy, definitions of stimulating protocols, using methods of assisted reproduction. Setting: Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk University and University Hospital Brno. Results: Embryo and oocyte cryopreservation are important methods of fertility preservation requiring controlled ovarian stimulation before the start of chemotherapy. Current studies demonstrante effectivenes of this special stimulating protocol and did not find negative side effects such a progression of the breast cancer. Since January 2016 to June 2016 we performed controlled ovarian stimulation and oocyte retrieval in three patients with breast cancer before chemotherapy. We used short stimulation protocol with recombinant FSH, GnRH agonists and letrozole and retrieved 13, 12 and 9 oocytes. We cryopreserved 8 and 6 embryos, one woman prefered freezing of 12 oocytes. During the stimulation estradiol level did not exceed 1,6 nmol/l. Conclusion: Neither the normal nor the cancerous cells in the breast react to the gonadotropins FSH, LH, nor to hCG. Conversely, there is a cellular proliferation and an increase in cancer cell lines with oestrogen receptors with exposure to oestrogen, and it is dose – dependent. The special stimulation protocol with FSH, GnRH agonists and letrozole is effective in gain of efficient amount of gamets with minimal increase of estradiole level. Current study reviews did not find higher risk of progression of breast cancer in association with ovarian stimulation. It is important to respect the recomendation of oncology committee and to effectively suppress the estradiol level.

• MeSH
• adjuvantní chemoterapie škodlivé účinky   MeSH
• antagonisté estrogenu MeSH
• antitumorózní látky hormonální škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• gonády účinky léků   účinky záření   MeSH
• indukce ovulace MeSH
• inhibitory aromatasy terapeutické užití   MeSH
• kryoprezervace MeSH
• letrozol MeSH
• lidé MeSH
• nádory prsu * epidemiologie   terapie   MeSH
• ovarium patologie   účinky léků   účinky záření   MeSH
• radioterapie škodlivé účinky   MeSH
• tamoxifen aplikace a dávkování   terapeutické užití   MeSH
• triptorelin-pamoát aplikace a dávkování   terapeutické užití   MeSH
• zachování plodnosti * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

T-2 toxin and its metabolite HT-2 toxin are one of the most toxic mycotoxins of type A-trichothecenes, which are produced mainly by Fusarium species. Therefore, study of Fusarium toxins T-2 toxin and HT-2 toxin is an essential issue because they could also play role in failures of reproductive functions as well as endocrine system of domestic animals. Assessment of the effect of A-trichothecene mycotoxin HT-2 toxin alone or combined with insulin-like growth factor (IGF-I), leptin and ghrelin on estradiol secretion by rabbit ovarian fragments in vitro was done. Rabbit ovarian fragments were incubated without (control group) or with HT-2 toxin, or its combinations with IGF-I, leptin and ghrelin at various concentrations for 24 h. Secretion of 17beta-estradiol was determined by ELISA. Firstly, HT-2 toxin at the doses 10 and 100 ng.ml(-1), but not at 1 ng.ml(-1) decreased 17beta-estradiol secretion by ovarian fragments. Secondly, 17beta-estradiol secretion was not affected by HT-2 toxin exposure combined with growth factor IGF-I, metabolic hormones leptin and ghrelin. In conclusion, HT-2 toxin has potent direct dose-dependent effects on ovarian steroidogenesis in rabbits. These direct effects of HT-2 mycotoxin on ovarian steroidogenesis could impact negatively on the reproductive performance of rabbits.

• MeSH
• estradiol krev   MeSH
• fixní kombinace léků MeSH
• ghrelin aplikace a dávkování   MeSH
• insulinu podobný růstový faktor I aplikace a dávkování   MeSH
• králíci MeSH
• kultivované buňky MeSH
• leptin aplikace a dávkování   MeSH
• ovarium účinky léků   metabolismus   MeSH
• T-2 toxin analogy a deriváty   toxicita   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH