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Female Reproduction: The Link between Basic Ovarian Events and the Microenvironment of the Oocyte

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 July 2022) | Viewed by 13261

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Special Issue Editor

Prof. Dr. Eva Nagyova

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Guest Editor

Institute of Animal Physiology and Genetics, Czech Academy of Sciences, 27721 Libechov, Czech Republic
Interests: oocyte; ovarian; Female Reproduction

Special Issue Information

Dear Colleagues,

Female fertility potential is based on the development of ovarian follicles, and ovarian pathologies constitute one of the main causes of infertility. The revelation of new targets involved in ovarian pathophysiology represents a significant scientific challenge. The fertilization of the mammalian oocyte requires tight interactions between the oocyte-cumulus extracellular matrix and spermatozoa. The expression of several essential components of the extracellular matrix has been confirmed in the mammalian ovarian follicles, and the impaired expression of their genes led to serious cumulus defects resulting in mice infertility. There is still an incomplete understanding of the specific changes that occur in the follicles leading to the modification of oocytes’ capacity to develop to the blastocyst stage. The elucidation of novel/unexplored signalling pathways that function as central regulators of cellular protein synthesis and metabolism in the oocyte microenvironment are of great interest.

Research focused on determining the follicular microenvironment produced by ovarian cells and its molecular characterisation could lead to the understanding of several fertility problems.

This Special Issue welcomes original research and review papers that aim to provide up-to-date reports on the link between basic ovarian events and the microenvironment of the oocyte.

Prof. Dr. Eva Nagyova
Guest Editor

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Keywords

female fertility
oocyte
ovarian pathologies
follicular microenvironment

Published Papers (4 papers)

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Research

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11 pages, 2357 KiB

Open AccessArticle

Role of Klotho as a Modulator of Oxidative Stress Associated with Ovarian Tissue Cryopreservation

by Boram Kim, Hyunho Yoon, Tak Kim and Sanghoon Lee

Int. J. Mol. Sci. 2021, 22(24), 13547; https://doi.org/10.3390/ijms222413547 - 17 Dec 2021

Cited by 8 | Viewed by 2702

Abstract

Ovarian tissue cryopreservation is the only option for preserving fertility in adult and prepubertal cancer patients who require immediate chemotherapy or do not want ovarian stimulation. However, whether ovarian tissue cryopreservation can ameliorate follicular damage and inhibit the production of reactive oxygen species in cryopreserved ovarian tissue remains unclear. Oxidative stress is caused by several factors, such as UV exposure, obesity, age, oxygen, and cryopreservation, which affect many of the physiological processes involved in reproduction, from maturation to fertilization, embryonic development, and pregnancy. Here, freezing and thawing solutions were pre-treated with N-acetylcysteine (NAC) and klotho protein upon the freezing of ovarian tissue. While both NAC and klotho protein suppressed DNA fragmentation by scavenging reactive oxygen species, NAC induced apoptosis and tissue damage in mouse ovarian tissue. Klotho protein inhibited NAC-induced apoptosis and restored cellular tissue damage, suggesting that klotho protein may be an effective antioxidant for the cryopreservation of ovarian tissue. Full article

(This article belongs to the Special Issue Female Reproduction: The Link between Basic Ovarian Events and the Microenvironment of the Oocyte)

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27 pages, 4876 KiB

Open AccessArticle

Protein Palmitoylation in Bovine Ovarian Follicle

by Svetlana Uzbekova, Ana-Paula Teixeira-Gomes, Aurélie Marestaing, Peggy Jarrier-Gaillard, Pascal Papillier, Ekaterina N. Shedova, Galina N. Singina, Rustem Uzbekov and Valerie Labas

Int. J. Mol. Sci. 2021, 22(21), 11757; https://doi.org/10.3390/ijms222111757 - 29 Oct 2021

Cited by 3 | Viewed by 2815

Abstract

Protein palmitoylation is a reversible post-translational modification by fatty acids (FA), mainly a palmitate (C16:0). Palmitoylation allows protein shuttling between the plasma membrane and cytosol to regulate protein stability, sorting and signaling activity and its deficiency leads to diseases. We aimed to characterize the palmitoyl-proteome of ovarian follicular cells and molecular machinery regulating protein palmitoylation within the follicle. For the first time, 84 palmitoylated proteins were identified from bovine granulosa cells (GC), cumulus cells (CC) and oocytes by acyl-biotin exchange proteomics. Of these, 32 were transmembrane proteins and 27 proteins were detected in bovine follicular fluid extracellular vesicles (ffEVs). Expression of palmitoylation and depalmitoylation enzymes as palmitoyltransferases (ZDHHCs), acylthioesterases (LYPLA1 and LYPLA2) and palmitoylthioesterases (PPT1 and PPT2) were analysed using transcriptome and proteome data in oocytes, CC and GC. By immunofluorescence, ZDHHC16, PPT1, PPT2 and LYPLA2 proteins were localized in GC, CC and oocyte. In oocyte and CC, abundance of palmitoylation-related enzymes significantly varied during oocyte maturation. These variations and the involvement of identified palmitoyl-proteins in oxidation-reduction processes, energy metabolism, protein localization, vesicle-mediated transport, response to stress, G-protein mediated and other signaling pathways suggests that protein palmitoylation may play important roles in oocyte maturation and ffEV-mediated communications within the follicle. Full article

(This article belongs to the Special Issue Female Reproduction: The Link between Basic Ovarian Events and the Microenvironment of the Oocyte)

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Review

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18 pages, 322 KiB

Open AccessReview

GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation

by Georgios Valsamakis, Konstantinos Valtetsiotis, Evangelia Charmandari, Irene Lambrinoudaki and Nikolaos F. Vlahos

Int. J. Mol. Sci. 2022, 23(4), 2287; https://doi.org/10.3390/ijms23042287 - 18 Feb 2022

Cited by 12 | Viewed by 3902

Abstract

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radiotherapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments. Full article

(This article belongs to the Special Issue Female Reproduction: The Link between Basic Ovarian Events and the Microenvironment of the Oocyte)

14 pages, 2588 KiB

Open AccessReview

Cumulus Extracellular Matrix Is an Important Part of Oocyte Microenvironment in Ovarian Follicles: Its Remodeling and Proteolytic Degradation

by Eva Nagyová, Lucie Němcová and Antonella Camaioni

Int. J. Mol. Sci. 2022, 23(1), 54; https://doi.org/10.3390/ijms23010054 - 21 Dec 2021

Cited by 10 | Viewed by 3041

Abstract

The extracellular matrix (ECM) is an essential structure with biological activities. It has been shown that the ECM influences gene expression via cytoskeletal components and the gene expression is dependent upon cell interactions with molecules and hormones. The development of ovarian follicles is a hormone dependent process. The surge in the luteinizing hormone triggers ovulatory changes in oocyte microenvironment. In this review, we discuss how proteolytic cleavage affects formation of cumulus ECM following hormonal stimulation; in particular, how the specific proteasome inhibitor MG132 affects gonadotropin-induced cytoskeletal structure, the organization of cumulus ECM, steroidogenesis, and nuclear maturation. We found that after the inhibition of proteolytic cleavage, gonadotropin-stimulated oocyte–cumulus complexes (OCCs) were without any signs of cumulus expansion; they remained compact with preserved cytoskeletal F-actin-rich transzonal projections through the oocyte investments. Concomitantly, a significant decrease was detected in progesterone secretion and in the expression of gonadotropin-stimulated cumulus expansion–related transcripts, such as HAS2 and TNFAIP6. In agreement, the covalent binding between hyaluronan and the heavy chains of serum-derived the inter-alpha-trypsin inhibitor, essential for the organization of cumulus ECM, was missing. Full article

(This article belongs to the Special Issue Female Reproduction: The Link between Basic Ovarian Events and the Microenvironment of the Oocyte)

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