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Pharmaceuticals
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Novel Regulators of Female Reproduction
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Novel Regulators of Female Reproduction

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 40420

Special Issue Editors

Prof. Dr. Alexander V. Sirotkin

E-Mail Website
Guest Editor
Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, Nabrezie mladeze 91, Slovakia
Interests: ovary; metabolism; hormones; growth factors; cell signaling; kinases; RNA interference; proliferation; apoptosis; environmental contaminants; phytotherapy
Prof. Dr. Adriana Kolesarova

E-Mail Website
Guest Editor
Slovak University of Agriculture in Nitra, Nitra, Slovakia
Interests: female reproduction; ovary; reproductive endocrinology; cell signaling; steroidogenesis; proliferation; apoptosis; phytonutrients; bioactive substances; reproductive toxicology

Special Issue Information

Dear Colleagues,

The Special Issue is focused on investigating the novel regulators of female reproduction in the laboratory and farm animals and humans.  Understanding the basic regulators of female reproduction is important for the preservation of the reproductive health and fertility of farm animals and humans, the regulation and treatment of reproductive disorders in animal production, biotechnology, assisted reproduction, and human and veterinary medicine. The study of the mechanisms regulating female reproduction including the formation of gametes (oocytes), their fertilization and pre-embryonic and postembryonic development is crucial for successful fertilization, reproduction, and fertility. This Special Issue covers a wide spectrum of regulators from environmental factors (temperature, metabolism, intake of calories, biological active nutrients, environmental contaminants) up to extracellular (hormones, growth factors) and intracellular (receptors, protein kinases, phosphatases, transcription factors, small RNA and genes) regulators of cell proliferation, apoptosis, necrosis, viability, and differentiation. These regulators can control ovarian folliculogenesis, oogenesis, embryogenesis, the development of the reproductive system and reproductive behavior.  Special attention is paid to bioactive substances of plant origin and by environmental and food contaminants affecting female reproduction and fertility, and female reproductive disorders including cellular stress disorganization of the cell cycle leading to uncontrolled cell division, differentiation, proliferation, and the inhibition of apoptosis and induction of tumorigenesis. Novel regulators including external and internal bioactive substances and their regulators can help in the characterization and improvement of the reproductive state, and the prevention, diagnostics, and treatment of reproductive disorders. 

Prof. Dr. Alexander V. Sirotkin
Prof. Adriana Kolesarova
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • female reproduction
  • ovary
  • ovarian follicle
  • oocyte
  • embryo
  • fecundity
  • hormone
  • growth factor
  • receptors
  • protein kinase
  • transcription factor
  • RNA interference
  • genes
  • metabolism
  • nutrition
  • plant molecules
  • environmental and food contaminants
  • reproductive behavior

Published Papers (7 papers)

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Research

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17 pages, 3345 KiB  
Article
Delaying Effects of Prolactin and Growth Hormone on Aging Processes in Bovine Oocytes Matured In Vitro
by Galina N. Singina, Ekaterina N. Shedova, Alexander V. Lopukhov, Olga S. Mityashova and Irina Y. Lebedeva
Pharmaceuticals 2021, 14(7), 684; https://doi.org/10.3390/ph14070684 - 16 Jul 2021
Cited by 5 | Viewed by 2497
Abstract
Aging processes accelerate dramatically in oocytes that have reached the metaphase-II (M-II) stage. The present work aimed to study the patterns and intracellular pathways of actions of prolactin (PRL) and growth hormone (GH) on age-associated changes in bovine M-II oocytes aging in vitro. [...] Read more.
Aging processes accelerate dramatically in oocytes that have reached the metaphase-II (M-II) stage. The present work aimed to study the patterns and intracellular pathways of actions of prolactin (PRL) and growth hormone (GH) on age-associated changes in bovine M-II oocytes aging in vitro. To this end, we analyzed spontaneous parthenogenetic activation (cytogenetic assay), apoptosis (TUNEL assay), and the developmental capacity (IVF/IVC) of in vitro-matured oocytes after prolonged culturing. Both PRL and GH reduced the activation rate of aging cumulus-enclosed oocytes (CEOs) and denuded oocytes (DOs), and their respective hormone receptors were revealed in the ova. The inhibitor of Src-family tyrosine kinases PP2 eliminated the effects of PRL and GH on meiotic arrest in DOs, whereas the MEK inhibitor U0126 only abolished the PRL effect. Furthermore, PRL was able to maintain the apoptosis resistance and developmental competence of aging CEOs. The protein kinase C inhibitor calphostin C suppressed both the actions of PRL. Thus, PRL and GH can directly support meiotic arrest in aging M-II oocytes by activating MAP kinases and/or Src-family kinases. The effect of PRL in maintaining the developmental capacity of aging oocytes is cumulus-dependent and related to the pro-survival action of the protein kinase C-mediated signal pathway. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
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Review

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22 pages, 6486 KiB  
Review
Phytoestrogens for the Management of Endometriosis: Findings and Issues
by Xia Cai, Min Liu, Bing Zhang, Shao-Jie Zhao and Shi-Wen Jiang
Pharmaceuticals 2021, 14(6), 569; https://doi.org/10.3390/ph14060569 - 14 Jun 2021
Cited by 17 | Viewed by 5326
Abstract
Endometriosis, a chronic disease characterized by recurrent pelvic pain and infertility, severely impacts the health and life quality of many women worldwide. Since phytoestrogens are commonly found in a variety of foods, and estrogen is a major pathological factor for the pathogenesis of [...] Read more.
Endometriosis, a chronic disease characterized by recurrent pelvic pain and infertility, severely impacts the health and life quality of many women worldwide. Since phytoestrogens are commonly found in a variety of foods, and estrogen is a major pathological factor for the pathogenesis of endometriosis, their possible involvement cannot be ignored. This review summarizes data on the relationship between phytoestrogen intake and endometriosis risk, and analyzes the findings from in vitro experiments, rodent endometriotic models, and human intervention trials. While favorable results were often obtained from endometrial primary cultures and animal models for resveratrol, isoflavones and puerarin, only resveratrol showed promising results in human intervention trials. Critical issues concerning the current study efforts are discussed: the possible reasons beneath the discrepant observations of estrogenic/anti-estrogenic effects by phytoestrogens; the complicated interplays between phytoestrogens and endogenous estrogens; the shortage of currently used animal models; the necessity to apply reasonable doses of phytoestrogens in experiments. It is expected that the analyses would help to more properly assess the phytoestrogens’ effects on the endometriosis pathogenesis and their potential values for preventive or therapeutic applications. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
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15 pages, 380 KiB  
Review
PPARγ Agonists: Emergent Therapy in Endometriosis
by Alexandre Vallée, Jean-Noël Vallée, Alain Le Blanche and Yves Lecarpentier
Pharmaceuticals 2021, 14(6), 543; https://doi.org/10.3390/ph14060543 - 06 Jun 2021
Cited by 8 | Viewed by 2775
Abstract
Endometriosis is one of the major gynecological diseases of reproductive-age women. This disease is characterized by the presence of glands and stroma outside the uterine cavity. Several studies have shown the major role of inflammation, angiogenesis, adhesion and invasion, and apoptosis in endometriotic [...] Read more.
Endometriosis is one of the major gynecological diseases of reproductive-age women. This disease is characterized by the presence of glands and stroma outside the uterine cavity. Several studies have shown the major role of inflammation, angiogenesis, adhesion and invasion, and apoptosis in endometriotic lesions. Nevertheless, the mechanisms underlying endometriotic mechanisms still remain unclear and therapies are not currently efficient. The introduction of new agents can be effective by improving the condition of patients. PPARγ ligands can directly modulate these pathways in endometriosis. However, data in humans remain low. Thus, the purpose of this review is to summarize the potential actions of PPARγ agonists in endometriosis by acting on inflammation, angiogenesis, invasion, adhesion, and apoptosis. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
19 pages, 2295 KiB  
Review
Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation
by Riccardo Gambioli, Gianpiero Forte, Giovanni Buzzaccarini, Vittorio Unfer and Antonio Simone Laganà
Pharmaceuticals 2021, 14(6), 504; https://doi.org/10.3390/ph14060504 - 25 May 2021
Cited by 34 | Viewed by 19517
Abstract
Pregnancy is a complex process, featuring several necessary changes in women’s physiology. Most women undergo healthy pregnancies; even so, several women experience reduced fertility or pathologies related to the pregnancy. In the last years, researchers investigated several molecules as promoters of fertility. Among [...] Read more.
Pregnancy is a complex process, featuring several necessary changes in women’s physiology. Most women undergo healthy pregnancies; even so, several women experience reduced fertility or pathologies related to the pregnancy. In the last years, researchers investigated several molecules as promoters of fertility. Among all, myo-inositol (myo-ins) represents a safe compound that proved useful in issues related to fertility and pregnancy. In fact, myo-ins participates in several signaling processes, including the pathways of insulin and gonadotropins, and, therefore, it is likely to positively affect fertility. In particular, several clinical trials demonstrate that its administration can have therapeutic effects in infertile women, and that it can also be useful as a preventive treatment during pregnancy. Particularly, myo-ins could prevent the onset of neural tube defects and the occurrence of gestational diabetes mellitus, promoting a trouble-free gestation. Due to the safety and efficiency of myo-ins, such a treatment may also substitute several pharmaceuticals, which are contraindicated in pregnancy. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
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10 pages, 864 KiB  
Review
The Influence of Plant Isoflavones Daidzein and Equol on Female Reproductive Processes
by Alexander V. Sirotkin, Saleh Hamad Alwasel and Abdel Halim Harrath
Pharmaceuticals 2021, 14(4), 373; https://doi.org/10.3390/ph14040373 - 17 Apr 2021
Cited by 13 | Viewed by 2700
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
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13 pages, 1318 KiB  
Review
Improving the Quality of Oocytes with the Help of Nucleolotransfer Therapy
by Michal Benc, Frantisek Strejcek, Martin Morovic, Alexandra Bartkova, Matej Murin, Ahmed Gad, Amelie Bonnet-Garnier, Florina Popovska Percinic and Jozef Laurincik
Pharmaceuticals 2021, 14(4), 328; https://doi.org/10.3390/ph14040328 - 02 Apr 2021
Cited by 1 | Viewed by 2924
Abstract
The nucleolus is an important nucleus sub-organelle found in almost all eukaryotic cells. On the one hand, it is known as a differentiated active site of ribosome biogenesis in somatic cells, but on the other hand, in fully grown oocytes, zygotes, and early [...] Read more.
The nucleolus is an important nucleus sub-organelle found in almost all eukaryotic cells. On the one hand, it is known as a differentiated active site of ribosome biogenesis in somatic cells, but on the other hand, in fully grown oocytes, zygotes, and early embryos (up to the major embryonic genome activation), it is in the form of a particular homogenous and compact structure called a fibrillar sphere. Nowadays, thanks to recent studies, we know many important functions of this, no doubt, interesting membraneless nucleus sub-organelle involved in oocyte maturation, embryonic genome activation, rRNA synthesis, etc. However, many questions are still unexplained and remain a mystery. Our aim is to create a comprehensive overview of the recent knowledge on the fibrillar sphere and envision how this knowledge could be utilized in further research in the field of biotechnology and nucleolotransfer therapy. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
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Other

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21 pages, 1329 KiB  
Systematic Review
The Utilization of Dehydroepiandrosterone as a Sexual Hormone Precursor in Premenopausal and Postmenopausal Women: An Overview
by Justine Tang, Li-Ru Chen and Kuo-Hu Chen
Pharmaceuticals 2022, 15(1), 46; https://doi.org/10.3390/ph15010046 - 29 Dec 2021
Cited by 14 | Viewed by 4206
Abstract
Dehydroepiandrosterone (DHEA), and its metabolite, dehydroepiandrosterone sulfate ester (DHEAS), are the most abundant circulating steroid hormones, and are synthesized in the zona reticularis of the adrenal cortex, in the gonads, and in the brain. The precise physiological role of DHEA and DHEAS is [...] Read more.
Dehydroepiandrosterone (DHEA), and its metabolite, dehydroepiandrosterone sulfate ester (DHEAS), are the most abundant circulating steroid hormones, and are synthesized in the zona reticularis of the adrenal cortex, in the gonads, and in the brain. The precise physiological role of DHEA and DHEAS is not yet fully understood, but these steroid hormones can act as androgens, estrogens, and neurosteroids, and perform many roles in the human body. Since both levels decline with age, use of DHEA supplements have gained more attention due to being advertised as an antidote to aging in postmenopausal women, who may have concerns on age-related diseases and overall well-being. However, current research has not reached an overall consensus on the effects of DHEA on postmenopausal women. This overview is a summary of the current literature, addressing the metabolic pathway for DHEA synthesis and utilization, as well as the effects of DHEA on premenopausal and postmenopausal women with disease states and other factors. As for the therapeutic effects on menopausal syndrome and other age-related diseases, several studies have found that DHEA supplementations can alleviate vasomotor symptoms, preserve the integrity of the immune system, reduce bone loss, and increase muscle mass. Intravaginal DHEA has shown significant beneficial effects in menopausal women with severe vulvovaginal symptoms. On the other hand, DHEA supplements have not shown definitive effects in cardiovascular disease, adrenal insufficiency, insulin sensitivity, and cognition. Due to inadequate sample sizes and treatment durations of current studies, it is difficult to assess the safety and efficacy of DHEA and draw reliable conclusions for the physiological role, the optimal dosage, and the effects on premenopausal and postmenopausal women; therefore, the study of DHEA warrants future investigation. Further research into the roles of these steroid hormones may bring us closer to a therapeutic option in the future. Full article
(This article belongs to the Special Issue Novel Regulators of Female Reproduction)
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