Kisspeptin as autocrine/paracrine regulator of human ovarian cell functions: Possible interrelationships with FSH and its receptor

Abstract. We hypothesized that the environmental contaminant benzene and the plant antioxidant quercetin may affect ovarian cell functions and that quercetin could offer protection against the adverse effects of benzene. This study aimed to examine the action of benzene, quercetin, and their combination on porcine ovarian granulosa cell functions. We elucidated the effects of benzene (20 µg mL−1), quercetin (at the doses 0, 1, 10, 100 µg mL−1), and their combination on ovarian granulosa cell functions (proliferation, apoptosis, and hormone release) in vitro using immunocytochemistry and enzyme immunoassay respectively. Benzene alone stimulated proliferation, apoptosis, and oxytocin release and inhibited progesterone and prostaglandin F release. Quercetin alone inhibited proliferation, apoptosis, and stimulated oxytocin release but did not affect progesterone and prostaglandin F release. When used in combination with benzene, quercetin promoted the inhibitory effect of benzene on progesterone release. Overall, these data suggest that benzene and quercetin have direct stimulatory and inhibitory effects, respectively, on basic ovarian functions. Moreover, no protective action of quercetin against the effects of benzene was found. Rather, it was found to enhance the effect of benzene on progesterone release. Therefore, quercetin cannot be considered for preventing or mitigating the effects of benzene on reproductive processes.

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Resveratrol directly affects ovarian cell sirtuin, proliferation, apoptosis, hormone release and response to follicle-stimulating hormone (FSH) and insulin-like growth factor I (IGF-I)

Reproduction Fertility and Development ◽

10.1071/rd18425 ◽

2019 ◽

Vol 31 (8) ◽

pp. 1378 ◽

Cited By ~ 4

Author(s):

Alexander Sirotkin ◽

Richard Alexa ◽

Attila Kádasi ◽

Erika Adamcová ◽

Saleh Alwasel ◽

...

Keyword(s):

Growth Factor ◽

Follicle Stimulating Hormone ◽

Sirtuin 1 ◽

Insulin Like Growth Factor ◽

Ovarian Cell ◽

Cell Functions ◽

Factor I ◽

Igf I ◽

Growth Factor I ◽

Stimulating Hormone

The objective of our study was to examine the influence of the plant polyphenol resveratrol (R) on the rapamycin signalling pathway (mammalian target of rapamycin; mTOR) and basic ovarian cell functions in mammalian targets, as well as on their response to the physiological hormonal stimulators follicle-stimulating hormone (FSH) and insulin-like growth factor I (IGF-I). Resveratrol was found to stimulate sirtuin 1 accumulation and apoptosis, inhibit proliferation, suppress P and promote T and E release. Alone, FSH promoted proliferation and had no effect on apoptosis, but had an inhibitory effect on these processes when combined with R. IGF-I alone stimulated proliferation and inhibited apoptosis and promoted P production but not that of T; however, in the presence of R, the addition of IGF-I switched from having an anti-apoptotic to a pro-apoptotic effect and stimulated T release, but it did not modify the effect of IGF-I on proliferation and P output. These observations: (1) demonstrate that R directly affects the basic ovarian cell functions of proliferation, apoptosis and steroidogenesis, (2) provide further evidence of the involvement of FSH and IGF-I in the regulation of these processes, (3) demonstrate the ability of R to prevent and even invert the effects of FSH and IGF-I on ovarian cells and (4) indicate that the effects of R may be mediated by the mTOR–sirtuin intracellular signalling system.

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The Influence of Plant Isoflavones Daidzein and Equol on Female Reproductive Processes

Pharmaceuticals ◽

10.3390/ph14040373 ◽

2021 ◽

Vol 14 (4) ◽

pp. 373

Author(s):

Alexander V. Sirotkin ◽

Saleh Hamad Alwasel ◽

Abdel Halim Harrath

Keyword(s):

Environmental Stressors ◽

Oxygen Species ◽

Female Reproduction ◽

Inhibitory Effects ◽

Hormone Production ◽

Ovarian Cell ◽

Cell Functions ◽

Physiological Processes ◽

Proliferation And Apoptosis ◽

Reproductive Processes

In this review, we explore the current literature on the influence of the plant isoflavone daidzein and its metabolite equol on animal and human physiological processes, with an emphasis on female reproduction including ovarian functions (the ovarian cycle; follicullo- and oogenesis), fundamental ovarian-cell functions (viability, proliferation, and apoptosis), the pituitary and ovarian endocrine regulators of these functions, and the possible intracellular mechanisms of daidzein action. Furthermore, we discuss the applicability of daidzein for the control of animal and human female reproductive processes, and how to make this application more efficient. The existing literature demonstrates the influence of daidzein and its metabolite equol on various nonreproductive and reproductive processes and their disorders. Daidzein and equol can both up- and downregulate the ovarian reception of gonadotropins, healthy and cancerous ovarian-cell proliferation, apoptosis, viability, ovarian growth, follicullo- and oogenesis, and follicular atresia. These effects could be mediated by daidzein and equol on hormone production and reception, reactive oxygen species, and intracellular regulators of proliferation and apoptosis. Both the stimulatory and the inhibitory effects of daidzein and equol could be useful for reproductive stimulation, the prevention and mitigation of cancer development, and the adverse effects of environmental stressors in reproductive biology and medicine.

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Can xylene and chia (Salvia hispanica L.) seed extract directly affect basic bovine ovarian cell functions?

Journal of Animal and Feed Sciences ◽

10.22358/jafs/69097/2017 ◽

2017 ◽

Vol 26 (2) ◽

pp. 109-115 ◽

Cited By ~ 4

Author(s):

A. Tarko ◽

A. Stochmalova ◽

S. Hrabovszka ◽

A. Vachanova ◽

A. Harrath ◽

...

Keyword(s):

Seed Extract ◽

Salvia Hispanica ◽

Ovarian Cell ◽

Cell Functions

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The mTOR System Can Affect Basic Ovarian Cell Functions and Mediate the Effect of Ovarian Hormonal Regulators

International Journal of Pharmacology ◽

10.3923/ijp.2015.570.578 ◽

2015 ◽

Vol 11 (6) ◽

pp. 570-578 ◽

Cited By ~ 8

Author(s):

Alexander V. Sirotkin ◽

Richard Alexa ◽

Petra Dekanova ◽

Attila Kadasi ◽

Aneta Stochmalov ◽

...

Keyword(s):

Ovarian Cell ◽

Cell Functions

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Effects of benzene on gilts ovarian cell functions alone and in combination with buckwheat, rooibos, and vitex

Environmental Science and Pollution Research ◽

10.1007/s11356-020-10739-7 ◽

2020 ◽

Vol 28 (3) ◽

pp. 3434-3444

Author(s):

Alexander V. Sirotkin ◽

Martina Macejková ◽

Adam Tarko ◽

Zuzana Fabova ◽

Abdulkarem Alrezaki ◽

...

Keyword(s):

Ovarian Cell ◽

Cell Functions

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Abatement of the Stimulatory Effect of Copper Nanoparticles Supported on Titania on Ovarian Cell Functions by Some Plants and Phytochemicals

Nanomaterials ◽

10.3390/nano10091859 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1859 ◽

Cited By ~ 1

Author(s):

Alexander V. Sirotkin ◽

Monika Radosová ◽

Adam Tarko ◽

Zuzana Fabova ◽

Iris Martín-García ◽

...

Keyword(s):

Cell Viability ◽

Copper Nanoparticles ◽

Plant Extracts ◽

Trypan Blue ◽

Stimulatory Action ◽

Ovarian Cell ◽

Cell Functions ◽

Ovarian Granulosa Cells ◽

17Β Estradiol ◽

Effect Of Copper

The application of nanoparticles has experienced a vertiginous growth, but their interaction with food and medicinal plants in organisms, especially in the control of reproduction, remains unresolved. We examined the influence of copper nanoparticles supported on titania (CuNPs/TiO2), plant extracts (buckwheat (Fagopyrum esculentum) and vitex (Vitex agnus-castus)), phytochemicals (rutin and apigenin), and their combination with CuNPs/TiO2 on ovarian cell functions, using cultured porcine ovarian granulosa cells. Cell viability, proliferation (PCNA accumulation), apoptosis (accumulation of bax), and hormones release (progesterone, testosterone, and 17β-estradiol) were analyzed by the Trypan blue test, quantitative immunocytochemistry, and ELISA, respectively. CuNPs/TiO2 increased cell viability, proliferation, apoptosis, and testosterone but not progesterone release, and reduced the 17β-estradiol output. Plant extracts and components have similar stimulatory action on ovarian cell functions as CuNPs/TiO2, but abated the majority of the CuNPs/TiO2 effects. This study concludes that (1) CuNPs/TiO2 can directly stimulate ovarian cell functions, promoting ovarian cell proliferation, apoptosis, turnover, viability, and steroid hormones release; (2) the plants buckwheat and vitex, as well as rutin and apigenin, can promote some of these ovarian functions too; and (3) these plant additives mitigate the CuNPs/TiO2’s activity, something that must be considered when applied together.

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Plant polyphenols can directly affect ovarian cell functions and modify toluene effects

Journal of Animal Physiology and Animal Nutrition ◽

10.1111/jpn.13461 ◽

2020 ◽

Author(s):

Alexander Sirotkin ◽

Zuzana Záhoranska ◽

Adam Tarko ◽

Zuzana Fabova ◽

Saleh Alwasel ◽

...

Keyword(s):

Plant Polyphenols ◽

Ovarian Cell ◽

Cell Functions

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Direct inhibitory effect of flaxseed on porcine ovarian granulosa cell functions

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0547 ◽

2019 ◽

Vol 44 (5) ◽

pp. 507-511

Author(s):

Aneta Štochmal’ová ◽

Abdel Halim Harrath ◽

Saleh Alwasel ◽

Alexander V. Sirotkin

Keyword(s):

Cell Proliferation ◽

Granulosa Cells ◽

Inhibitory Effect ◽

Ovarian Cell ◽

Cell Functions ◽

Ovarian Granulosa Cell ◽

Igf I ◽

Direct Inhibitory Effect ◽

Reproductive Processes ◽

Flaxseed Extract

Flaxseed is useful as a functional food and alternative medicine owing to its beneficial health effects. Its action on ovarian cell functions and interrelationships with the upstream hormonal regulators remain unknown. Our aim was to examine the direct influence of flaxseed extract on basal porcine ovarian functions (proliferation, apoptosis), leptin release, and response to insulin-like growth factor I (IGF-I). First, we examined the effect of flaxseed extract on the accumulation of proliferation (PCNA) and apoptosis (Bax) markers and on leptin release in cultured porcine ovarian granulosa cells. Next, granulosa cells were cultured with IGF-I with and without flaxseed extract and analyzed for PCNA and Bax accumulation by quantitative immunocytochemistry and for leptin release by radioimmunoassay. Flaxseed decreased the accumulation of PCNA and increased that of Bax at all doses and reduced leptin output at 100 μg/mL. In contrast, IGF-I promoted PCNA accumulation and suppressed Bax. Flaxseed did not modify IGF-I action on these parameters. Thus, we showed that flaxseed influences porcine reproductive processes, having a direct effect on the ovary and the ability to affect ovarian cell proliferation, apoptosis, and leptin release. Furthermore, we confirmed the pro-proliferative and antiapoptotic actions of IGF-I but showed that flaxseed action on ovarian cell proliferation and apoptosis is not due to changes in the cell response to IGF-I. The potential direct anti-reproductive action of flaxseed needs to be considered during its application in nutrition, medicine, and animal production.

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