Role of EGFR expressed on the granulosa cells in the pathogenesis of polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological disorders affecting between 6 to 20% of reproductive aged women. However, the etiology of PCOS is still unclear. Epidermal growth factor receptor (EGFR) plays a critical role in the growth and development of ovarian follicles. In our previous study, we showed that the expression level of EGFR was significantly higher in the cumulus granulosa cells from women with PCOS than that of normal women, suggesting that EGFR may play a potential role in the pathogenesis of PCOS. The present study further evaluated the association between EGFR and PCOS through both in clinical observation and animal experiments. We firstly validated the differential expression of EGFR in cumulus granulosa cells between PCOS patients and normal subjects by qRT-PCR and immunofluorescence staining. Then we generated a mouse model (n=20) of PCOS by injecting dehydroepiandrosterone (DHEA). The PCOS mice were then injected with an E corpus GFR inhibitor (AG1478) (n=10), which significantly improved the sex hormone levels in the estrous cycle stage, and the serum levels of LH, FSH and testosterone were compared with the PCOS mice without EGFR inhibitor treatment (n=10). Decreasing the expression level of EGFR in the PCOS mice also improved the ovulatory function of their ovaries which was indicated by the multifarious follicle stage in these mice as compared with the PCOS mice without EGFR inhibitor treatment. Also, the number of corpopa lutea were higher in the control group and the EGFR inhibitor treated group than in the PCOS group. The sex hormone levels and reproductive function were not significantly different between the control mice and the PCOS mice treated with the EGFR inhibitor. Our results demonstrated that EGF/EGFR signaling affected the proliferation of cumulus granulosa cells, oocyte maturation and meiosis, and played a potential role in the pathogenesis of PCOS. Therefore, the selective inhibition of EGFR may serve as a novel strategy for the clinical management of PCOS.

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

“…PYGM is also expressed in T lymphocytes, where it plays a crucial role in the control of IL2–stimulated T-cell migration and proliferation in an EGFR-dependent manner ( 52 , 65 ). EGF/EGFR signaling was reported to affect the proliferation of cumulus GCs, oocyte maturation and meiosis and play a potential role in the pathogenesis of PCOS ( 66 ). We hypothesize that EGFR may activate PYGM to regulate T cell migration and proliferation in PCOS cases.…”

The expression of CD24 in granulosa cells of patients with polycystic ovary syndrome affects the clinical outcome of assisted reproductive technology

“…An animal experiment showed that suppressing EGFR levels by treating PCOS mice with EGFR inhibitor promoted a huge improvement in the ovulatory function and sex hormone levels, including the oestrus cycle, LH/FSH ratio, testosterone levels, morphology of the ovary and probability of ovulation. Then it demonstrated that EGF/EGFR signaling affected the proliferation of cumulus granulosa cells, oocyte maturation and meiosis, and played a potential role in the pathogenesis of PCOS [20]. Based on the above results, it can be speculated that the high expression of CD24 in GCs of PCOS patients may be related to abnormal oocyte development and ovulation disorder, but the speci c mechanism needs to be further investigated.…”

CircRAB11A act as miR-24-5p sponge promotes proliferation and resists apoptosis of chicken granulosa cell via EGFR/ERK1/2 and RAB11A/ PI3K/AKT pathways

“…A pervious study found that RAB11A could regulate ovarian cancer cells ( Wang et al, 2022b ; Wang et al, 2022c ). On the other hand, EGFR (also known as ErbB1 or HER1), a single transmembrane protein and receptor tyrosine kinase (RTK), has been shown to regulate various functions of the ovary such as follicle development, oocyte maturation, GC proliferation, differentiation, and steroid production through its interaction with EGF ( Zheng, et al, 2017 ; Zhang, et al, 2022 ). Additionally, EGFR often regulates the function of GCs through the ERK1/2 and PI3K/AKT pathways in chickens ( Wang, et al, 2007 ; Lin et al, 2011 ; Wu, et al, 2019 ).…”