Seminal extracellular vesicles subsets modulate gene expression in cumulus cells of porcine in vitro matured oocytes

Mateo‐Otero, Yentel; Yeste, Marc; Roca, Jordi; Llavanera, Marc; Bucci, Diego; Galeati, Giovanna; Spinaci, Marcella; Barranco, Isabel

doi:10.1038/s41598-022-22004-7

Cited by 12 publications

(5 citation statements)

References 77 publications

(114 reference statements)

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“…In combination with BLM for cancer, abnormal expression of STAR, CYP11A1, and HSD3B1 led to hormone secretion disorder [55]. The secreted progesterone and estradiol of CCs are concerned with the expression of STAR, CYP11A1, and HSD3B1 [57,58]. In this study, the inhibition of CDKN1A significantly increased the mRNA levels of STAR, CYP11A1, and HSD3B1 in bovine CCs and significantly promoted the secretion of E 2 and P 4 .…”

Section: Discussionmentioning

confidence: 51%

miR-302d Targeting of CDKN1A Regulates DNA Damage and Steroid Hormone Secretion in Bovine Cumulus Cells

Liu,

Zhang,

Zheng

et al. 2023

Genes

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(1) Background: DNA damage in cumulus cells hinders oocyte maturation and affects steroid hormone secretion. It is crucial to identify the key factors that regulate cellular DNA damage and steroid hormone secretion. (2) Methods: Treatment of bovine cumulus cells with bleomycin to induce DNA damage. The effects of DNA damage on cell biology were determined by detecting changes in DNA damage degree, cell cycle, viability, apoptosis, and steroid hormones. It was verified that mir-302d targeted regulation of CDKN1A expression, and then affected DNA damage and steroid hormone secretion in cumulus cells. (3) Results: Bleomycin induced increased DNA damage, decreased G1-phase cells, increased S-phase cells, inhibited proliferation, promoted apoptosis, affected E2 and P4 secretion, increased CDKN1A expression, and decreased miR-302d expression. Knockdown of CDKN1A reduced DNA damage, increased G1-phase cells, decreased G2-phase cells, promoted proliferation, inhibited apoptosis, increased E2 and P4 secretion, and increased the expression of BRCA1, MRE11, ATM, CDK1, CDK2, CCNE2, STAR, CYP11A1, and HSD3B1. The expression of RAD51, CCND1, p53, and FAS was decreased. Overexpression of CDKN1A resulted in the opposite results. miR-302d targets CDKN1A expression to regulate DNA damage and then affects the cell cycle, proliferation, apoptosis, steroid hormone secretion, and the expression of related genes. (4) Conclusions: miR-302d and CDKN1A were candidate molecular markers for the diagnosis of DNA damage in bovine cumulus cells.

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Section: Discussionmentioning

confidence: 51%

miR-302d Targeting of CDKN1A Regulates DNA Damage and Steroid Hormone Secretion in Bovine Cumulus Cells

Liu,

Zhang,

Zheng

et al. 2023

Genes

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“…Moreover, Hung et al [ 39 ] showed that both murine and bovine COCs supplemented with EVs derived from bovine FF also significantly increased cumulus expansion during IVM. However, this effect does not always occur, as it has been reported that porcine COCs supplemented with EVs obtained from the physiologically closer porcine FF [ 43 ] or seminal plasma [ 44 ] did not show increased expansion. Similarly, porcine ffEVs did not enhance the expansion of murine COCs [ 43 ].…”

Section: Discussionmentioning

confidence: 98%

Follicular Fluid-Derived Extracellular Vesicles Influence on In Vitro Maturation of Equine Oocyte: Impact on Cumulus Cell Viability, Expansion and Transcriptome

Gabryś,

Gurgul,

Szmatoła

et al. 2024

IJMS

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Cumulus cell (CC) expansion is pivotal for oocyte maturation, during which CCs release factors that initiate paracrine signaling within the follicular fluid (FF). The FF is abundant in extracellular vesicles (EVs) that facilitate intercellular communication. Although bovine and murine EVs can control cumulus expansion, these effects have not been observed in equines. This study aimed to assess the impact of FF-derived EVs (ffEVs) on equine CC expansion, viability, and transcriptome. Cumulus–oocyte complexes (COCs) that underwent in vitro maturation (IVM) in the presence (200 µg protein/mL) or absence (control) of ffEVs were assessed for cumulus expansion and viability. CCs were isolated after 12 h of IVM, followed by RNA extraction, cDNA library generation, and subsequent transcriptome analysis using next-generation sequencing. Confocal microscopy images illustrated the internalization of labeled ffEVs by CCs. Supplementation with ffEVs significantly enhanced cumulus expansion in both compacted (Cp, p < 0.0001) and expanded (Ex, p < 0.05) COCs, while viability increased in Cp groups (p < 0.01), but decreased in Ex groups (p < 0.05), compared to the controls. Although transcriptome analysis revealed a subtle effect on CC RNA profiles, differentially expressed genes encompassed processes (e.g., MAPK and Wnt signaling) potentially crucial for cumulus properties and, consequently, oocyte maturation.

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“…For experiments with heat stress, treatments were arranged in a 2 × 4 factorial design with primary effects of incubation temperature during maturation (38.5°C vs. 41°C) and with four culture mediums: non-supplemented control (NC), vehicle [DPBS (1X)], EVs derived from granulosa cells subjected to the normal physiological body temperature of the cow (38.5°C) (normal EVs: N-EVs) or EVs derived from granulosa cells subjected to thermal stress (42°C) (stressed EVs: S-EVs). In brief, COCs were incubated with 20% v/v of DPBS (1X), and treatments with GC-EVs were offset with equal concentrations of total protein (0.3 mg/mL) assessed using a NanoDrop 2000 Spectrophotometer (Thermo Scientific; Waltham, MA, United States), selected based on previous literature ( Almiñana et al, 2017 ; Alcântara-Neto et al, 2020a ; Alcântara-Neto et al, 2020b ; Abumaghaid et al, 2022 ; Mateo-Otero et al, 2022 ). For all experimental groups, control COCs matured at a temperature of 38.5°C throughout the maturation period (23 ± 1 h), while thermally stressed COCs were subjected to an initial 8 h priming period at 38.5°C and then transferred to 41°C in an atmosphere of 5% CO 2 in humidified air for the remaining 15 ± 1 h of the 23 ± 1 h maturation period.…”

Section: Methodsmentioning

confidence: 99%

Granulosa cell-derived extracellular vesicles mitigate the detrimental impact of thermal stress on bovine oocytes and embryos

Menjivar

Gad

Gebremedhn

et al. 2023

Front. Cell Dev. Biol.

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Climate change-induced global warming results in rises in body temperatures above normal physiological levels (hyperthermia) with negative impacts on reproductive function in dairy and beef animals. Extracellular vesicles (EVs), commonly described as nano-sized, lipid-enclosed complexes, harnessed with a plethora of bioactive cargoes (RNAs, proteins, and lipids), are crucial to regulating processes like folliculogenesis and the initiation of different signaling pathways. The beneficial role of follicular fluid-derived EVs in inducing thermotolerance to oocytes during in vitro maturation (IVM) has been evidenced. Here we aimed to determine the capacity of in vitro cultured granulosa cell-derived EVs (GC-EVs) to modulate bovine oocytes’ thermotolerance to heat stress (HS) during IVM. Moreover, this study tested the hypothesis that EVs released from thermally stressed GCs (S-EVs) shuttle protective messages to provide protection against subsequent HS in bovine oocytes. For this, sub-populations of GC-EVs were generated from GCs subjected to 38.5°C (N-EVs) or 42°C (S-EVs) and supplemented to cumulus-oocyte complexes (COCs) matured in vitro at the normal physiological body temperature of the cow (38.5°C) or HS (41°C) conditions. Results indicate that S-EVs improve the survival of oocytes by reducing ROS accumulation, improving mitochondrial function, and suppressing the expression of stress-associated genes thereby reducing the severity of HS on oocytes. Moreover, our findings indicate a carryover impact from the addition of GC-EVs during oocyte maturation in the development to the blastocyst stage with enhanced viability.

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Seminal extracellular vesicles subsets modulate gene expression in cumulus cells of porcine in vitro matured oocytes

Cited by 12 publications

References 77 publications

miR-302d Targeting of CDKN1A Regulates DNA Damage and Steroid Hormone Secretion in Bovine Cumulus Cells

miR-302d Targeting of CDKN1A Regulates DNA Damage and Steroid Hormone Secretion in Bovine Cumulus Cells

Follicular Fluid-Derived Extracellular Vesicles Influence on In Vitro Maturation of Equine Oocyte: Impact on Cumulus Cell Viability, Expansion and Transcriptome

Granulosa cell-derived extracellular vesicles mitigate the detrimental impact of thermal stress on bovine oocytes and embryos

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