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

Miller, Irit; Chuderland, Dana; Ron-El, Raphaël; Shalgi, Ruth; Ben‐Ami, Ido

doi:10.1210/jc.2015-2312

Cited by 32 publications

(22 citation statements)

References 32 publications

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“…WT and Il1a ‐KO female mice were primed the gonadotropins—PMSG (Syncro‐part, Sanofi, Paris, France) and hCG (Sigma–Aldrich, St Louis, MO), as previously described (Miller et al, ). Ovulated cumulus‐oocyte‐complexes were isolated from the oviductal ampulla into M2 medium (Sigma–Aldrich), 16–18 hr after hCG administration.…”

Section: Methodsmentioning

confidence: 99%

“…The FSh‐17 rat GC line was a gift from Prof. Abraham Amsterdam (Weizmann Institute of Science, Rehovot, Israel) (Sprengel, ). GCs were cultured in DMEM/F12 medium supplemented with 10% charcoal‐stripped fetal calf serum (CS FCS) (Invitrogen, Grand Island, NY), 2 mM L‐glutamine, penicillin (10,000 IU/ml), and streptomycin (10 mg/ml) (Biological Industries, Beit‐Ha'emek, Israel), in six‐well plates, as previously described (Miller et al, ). The cells were serum‐starved for 16 hr in DMEM/F12 (1% CS FCS, 2 mM L‐glutamine, penicillin [10,000 IU/ml], and streptomycin [10 mg/ml]), stimulated with recombinant IL1A (400‐ML; R&D systems, Minneapolis, MN) in ascending doses for 24 hr, washed in PBS, and subjected to RNA extraction.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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. We found elevated Fshr transcript abundance, as assessed by quantitative PCR, in primary GCs isolated from Il1a-knockout compared to wild-type mice, and that the expression of FSHR is significantly higher in Il1a-knockout compared to wild-type ovaries. Supplementing GC cultures with recombinant IL1A significantly lowered Fshr expression in these cells. In accordance with the Fshr expression pattern, proliferation of GCs was higher in follicles from Il1a-knockout mice compared to wild-type mice, as indicated by the MKI67 immunohistochemical staining. Furthermore, treating wild-type mice with anakinra, an IL1 receptor 1 antagonist, significantly increased the expression of Fshr in primary GCs from treated compared to control mice. These data highlight an important interdependency between the potent pro-inflammatory cytokine IL1A and Fshr expression.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…Miller et al (38) showed that GnRH agonist triggering induces a direct effect on PEDF/VEGF balance in GCs inversely to hCG. Human primary GCs stimulated in vitro by GnRH agonist secreted higher levels of PEDF and lower levels of VEGF compared with cells not treated with GnRH agonist.…”

Section: Vegf and Pedfmentioning

confidence: 99%

Standard human chorionic gonadotropin versus double trigger for final oocyte maturation results in different granulosa cells gene expressions: a pilot study

Haas

Ophir

Machtinger

et al. 2016

Fertility and Sterility

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Objective: To investigate the messenger RNA (mRNA) expression of reproduction-related genes in granulosa cells (GCs) of patients triggered with hCG compared with patients triggered with GnRH agonist and hCG (double trigger) for final oocyte maturation. Design: Granulosa cells were obtained at the time of oocyte retrieval, and gene expression was analyzed using quantitative real-time polymerase chain reaction. Setting: Referral center. Patient(s): Fifteen women undergoing controlled ovarian hyperstimulation for IVF who received hCG for final follicular maturation and in a subsequent IVF cycle received double trigger. Intervention(s): Granulosa cells collection. Main Outcome Measure(s): The expression of genes related to ovarian hyperstimulation syndrome, gap junction, and epidermal-like growth factor in GCs. Result(s): The mRNA expressions of amphiregulin (2.1 vs.

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“…After a gonadotropin stimulation, the ovaries of the Lxr−/− mice harvest large hemorrhagic follicles with an exaggerated inflammatory and ovulatory response. This signals a diagnosis of OHSS, which is characterized by the excessive accumulation of vasoactive and angiogenic substances activating the vascular epithelial growth factor (VEGF) and interleukin (IL) 6 signaling, leading to a systemic inflammatory response, and variable clinical manifestations of cardiovascular collapse, septic shock, and thromboembolism in the most severe cases [48,49,50,51,52,53]. …”

Section: Lxrs and Their Ligands In The Ovarymentioning

confidence: 99%

Liver X Receptors: A Possible Link between Lipid Disorders and Female Infertility

Dallel

Tauveron

Brugnon

et al. 2018

IJMS

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A close relationship exists between cholesterol and female reproductive physiology. Indeed, cholesterol is crucial for steroid synthesis by ovary and placenta, and primordial for cell structure during folliculogenesis. Furthermore, oxysterols, cholesterol-derived ligands, play a potential role in oocyte maturation. Anomalies of cholesterol metabolism are frequently linked to infertility. However, little is known about the molecular mechanisms. In parallel, increasing evidence describing the biological roles of liver X receptors (LXRs) in the regulation of steroid synthesis and inflammation, two processes necessary for follicle maturation and ovulation. Both of the isoforms of LXRs and their bona fide ligands are present in the ovary. LXR-deficient mice develop late sterility due to abnormal oocyte maturation and increased oocyte atresia. These mice also have an ovarian hyper stimulation syndrome in response to gonadotropin stimulation. Hence, further studies are necessary to explore their specific roles in oocyte, granulosa, and theca cells. LXRs also modulate estrogen signaling and this could explain the putative protective role of the LXRs in breast cancer growth. Altogether, clinical studies would be important for determining the physiological relevance of LXRs in reproductive disorders in women.

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

Abstract: GnRH-a triggering induces a direct effect on PEDF/VEGF balance in granulosa cells inversely to hCG. Our results suggest a novel elucidation to the GnRH-a triggering-mediated risk reduction of OHSS and may clarify the pros and cons of this triggering method.

Cited by 32 publications

References 32 publications

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

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

Standard human chorionic gonadotropin versus double trigger for final oocyte maturation results in different granulosa cells gene expressions: a pilot study

Liver X Receptors: A Possible Link between Lipid Disorders and Female Infertility

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