Fyn and argonaute 2 participate in maternal-mRNA degradation during mouse oocyte maturation.

Fertilization triggers physiological degradation of maternal-mRNAs, which are then replaced by embryonic transcripts. Ample evidence suggests that Argonaut 2 (AGO2) is a possible post-fertilization regulator of maternal-mRNAs degradation; but its role in degradation of maternal-mRNAs during oocyte maturation remains obscure. Fyn, a member of the Src family kinases (SFKs), and an essential factor in oocyte maturation, was reported to inhibit AGO2 activity in oligodendrocytes.

Pigment epithelium-derived factor negates oxidative stress in mouse oocytes.

Molecular changes, caused by various environmental factors, affect the quality and developmental potential of oocytes. Oxidative stress (OS) is a major factor involved in various gynecologic disorders and/or in aging. Recent studies suggest that elevated reactive oxygen species (ROS) hamper oocyte quality and future embryonic development.

Pigment epithelium-derived factor (PEDF) negates hyperandrogenic PCOS features.

Polycystic ovary syndrome (PCOS), one of the most common female endocrine disorder, is a prevalent cause of infertility. Hyperandrogenism is a key feature in PCOS and is correlated with increased expression of VEGF and cytokines in the ovaries. We have previously shown that pigment epithelium-derived factor (PEDF), an endogenous protein, presents potent anti-angiogenic and anti-inflammatory activities in the ovary and negates the effects of cytokines and VEGF.

Pre-ovulatory intercellular regulation of miR-125a-3p within mouse ovarian follicles.

miR-125a-3p, a post-transcription regulator of Fyn kinase, is expressed in mouse pre-ovulatory follicles; its expression within the follicle decreases toward ovulation. Our aim was to follow the synthesis of miR-125a-3p and regulation of its expression in all follicular compartments, focusing on intercellular communication. Mural granulosa cells (GCs) or cumulus cells (CCs) were transfected with either scrambled-miR (negative control) or miR-125a-3p mimic.

Elucidating the role of pigment epithelium-derived factor (PEDF) in metabolic PCOS models.

PCOS is the most common endocrinopathy in women; associated with obesity and insulin resistance (IR). IR leads to accumulation of advanced-glycation-end-products (AGEs) and their receptor, RAGE. PCOS patients have increased levels of vascular endothelial growth factor (VEGF), interleukin 6/8 (IL-6/8) and anti-Mϋllerian-hormone (AMH).

Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments.

Meiotically arrested oocytes are characterized by the presence of the nuclear structure known as germinal-vesicle (GV), the breakdown of which (GVBD) is associated with resumption of meiosis. Fyn is a pivotal factor in resumption of the first meiotic division; its inhibition markedly decreases the fraction of oocytes undergoing GVBD. Here, we reveal that in mouse oocytes Fyn is post-transcriptionally regulated by miR-125a-3p.

Interleukin 1-alpha deficiency increases the expression of Follicle-stimulating hormone receptors in granulosa cells.

Follicle-stimulating hormone receptor (FSHR) is a pivotal regulator of ovarian response to hormonal stimulation. Inflammatory conditions have been linked to lower FSHR expression in granulosa cells (GCs) as well as an attenuated response to hormonal stimulation. The current study aimed to reveal if deficiency and/or blockage of the pro-inflammatory cytokine interleukin 1-alpha (IL1A) increased Fshr expression in rodent GCs.

The Dual Role of PEDF in the Pathogenesis of OHSS: Negating Both Angiogenic and Inflammatory Pathways.

Context: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproductive technologies. This complex syndrome is known to involve massive angiogenesis and inflammation. We have previously established the anti-angiogenic involvement of pigment epithelium-derived factor (PEDF) in the pathophysiology and treatment of OHSS.

GnRH Agonist Triggering Modulates PEDF to VEGF Ratio Inversely to hCG in Granulosa Cells.

Context: GnRH agonist (GnRH-a) triggering is associated with a reduced risk of ovarian hyperstimulation syndrome (OHSS) compared with human chorionic gonadotropin (hCG) in assisted reproduction technology cycles. We have shown that ovarian pigment epithelium derived factor (PEDF), a potent antiangiogenic factor, counteracts vascular endothelial growth factor (VEGF) expression and that OHSS is correlated with hCG-induced impaired PEDF to VEGF ratio.

Objective: The objective of the study was to explore whether GnRH-a triggering could directly modulate PEDF/VEGF balance in granulosa cells.

Gonadotrophin-releasing hormone agonists for fertility preservation: unraveling the enigma?

Study Question: Can gonadotrophin-releasing hormone agonists (GnRH-a) preserve long-term fertility when administered prior to and concomitantly with chemotherapy?

Summary Answer: GnRH-a display a differential protective effect on fertility, depending upon the specific chemotherapy-induced mechanism of ovarian injury.

What Is Known Already: The role of GnRH-a in fertility preservation has been constantly debated and their use is considered experimental due to conflicting clinical evidence and paucity of data regarding their mechanism for ovarian protection.

Study Design, Size, Duration: In vivo model: 7-8 weeks old imprinting control region (ICR) mice were injected with GnRH-a (Leuprolide-acetate) or saline prior to and concomitantly with cyclophosphamide, doxorubicin or saline and sacrificed at various time-points on a longitudinal follow-up; 24 h (n = 36), 1 week (n = 40), 1 month (n = 36) and 9 months (n = 66) post chemotherapy treatment.