Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development

Zimmermann, Ralf; Hartman, T. D.; Kavic, Suzanne; Pauli, Samuel A.; Bőhlen, Peter; Sauer, Mark V.; Kitajewski, Jan

doi:10.1172/jci200318740

Cited by 103 publications

(42 citation statements)

References 27 publications

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“…Along this line, injection of VEGFA to rat ovaries increased the number of antral follicles (Danforth et al 2003) and elevated the number of ovulating oocytes (Iijima et al 2005). Additionally, the blockage of VEGF receptor 2 (VEGFR2) by neutralizing antibodies attenuated the formation of pre-antral follicles (Zimmermann et al 2003). VEGF receptor 1 (VEGFR1), which delivers the VEGF signal intracellularly, is upregulated in theca cells of large follicles after pregnant mare serum gonadotropin (PMSG) administration in gilts (Shimizu et al 2002).…”

Section: The Involvement Of Angiogenesis In the Ovary And Df Selectionmentioning

confidence: 99%

Ovarian Folliculogenesis

Rimon-Dahari¹,

Yerushalmi-Heinemann²,

Alyagor³

et al. 2016

Results and Problems in Cell Differentiation

196

111

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Gosipol is a substances contained in extracted cotton seed which is thought to have the antifertility ability therefore it is often used as a herbal contraceptive. The aim of this study were to assess the folliculogenesis in mice after administrated with cottonseed extract. 60 female mice strain DDY which was 14-15 weeks old and 30-35 g body weight were divided into five groups and given cottonseed extract each 0; 1,5; 2,1 and 2,7 g/kg BW for 5, 10, 15, 24, and 24 + 10 days (without cottonseed treatment). At the end of the treatment period, mice was euthanasia to observe follicular development histomorphology (each three mice of each treatment). Mice estrous status were evaluated based on the description of the vaginal smear cells with Giemsa staining. The results showed that the number of developing follicles was low (P < 0.05) compared with control after 5 days cottonseed extract administration at dose 2,7 g/kg BW that were 23 ± 3,6. At dose 1,5 and 2,1 g/kg BW the number of follicles was low after 24 days that were 25 ± 10,4 and 27 ± 3,5. Recovery effects of follicle number after cottonseed extract administration for 24 days was the best at a dose of 1,5 g/kg BW. Prolonge of estrous cycle occured in mice which were administrated the cottonseed extract of at all dose treatment. In conclusion, although the decrease in the number of developing follicles and prolonge of estrous cycles occurred after cottonseed extract administration, but these effects are reversible after the administration ended. Abstrak Gosipol adalah zat yang terkandung dalam ekstrak biji kapas dan diduga mempunyai kemampuan antifertilitas sehingga sering digunakan sebagai bahan herbal kontrasepsi. Penelitian ini bertujuan mengkaji gambaran folikulogenesis pada mencit yang diberi ekstrak biji kapas. Sebanyak 60 ekor induk mencit betina strain DDY berumur 14-15 minggu dengan bobot badan 30-35 g dibagi menjadi 4 kelompok dan diberi ekstrak biji kapas masing-masing 0; 1,5; 2,1 dan 2,7 g/kg BB selama 5, 10, 15, 24 dan 24 + 10 hari (tanpa pemberian ekstrak biji kapas). Pada setiap akhir waktu pengamatan, mencit di-euthanasia untuk mengamati histomorfologi perkembangan folikel (masing-masing tiga ekor dari tiap perlakuan). Status estrus mencit dievaluasi berdasarkan gambaran sel dari ulas vagina dengan pewarnaan Giemsa. Hasil penelitian menunjukkan bahwa jumlah folikel rendah (P < 0,05) dibandingkan dengan kontrol setelah 5 hari pemberian ekstrak biji kapas dengan dosis 2,7 g/kg BB yaitu 23 ± 3,6. Pada dosis 1,5 dan 2,1 g/kg BB jumlah folikel menjadi rendah setelah 24 hari yaitu 25 ± 10,4; 27 ± 3,5. Efek pemulihan jumlah folikel setelah pemberian ekstrak biji kapas selama 24 hari paling baik pada dosis 1,5 g/kg BB. Pemanjangan siklus estrus terjadi pada mencit yang diberi ekstrak bji kapas pada semua dosis perlakuan. Berdasarkan hasil tersebut dapat disimpulkan bahwa walaupun terjadi penurunan jumlah folikel yang berkembang dan terjadi pemanjangan siklus estrus setelah pemberian ekstrak biji kapas, tetapi efek tersebut bersifat reversible setelah pe...

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Section: The Involvement Of Angiogenesis In the Ovary And Df Selectionmentioning

confidence: 99%

Ovarian Folliculogenesis

Rimon-Dahari¹,

Yerushalmi-Heinemann²,

Alyagor³

et al. 2016

Results and Problems in Cell Differentiation

196

111

View full text Add to dashboard Cite

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“…It is probable that the higher expression of sVEGFR1 prevents the VEGF–VEGFR2 interaction to avoid an over growth of blood vessels and a response of uncontrolled proliferation and survival of follicular cells. It is import to note that VEGFR1 and sVEGFR1 have ten times more affinity for the ligand (Kd __ 15 pM) than VEGFR2 and sVEGFR2 (Kd __150 pM; Ferrara ) and that VEGFR2 is the most active receptor on ovarian follicles (Greenaway et al., ; Wulff, Wilson, Wiegand, Rudge, & Fraser, ; Zimmermann et al., ).…”

Section: Discussionmentioning

confidence: 99%

Reduction in the mRNA expression of sVEGFR1 and sVEGFR2 is associated with the selection of dominant follicle in cows

Serrano

Guzmán

Hernández‐Coronado

et al. 2016

Reprod Domestic Animals

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The vascular endothelial growth factor (VEGF) is essential for follicular development by promoting follicular angiogenesis, as well as for the proliferation and survival of granulosa cells. The biological effects of VEGF are regulated by two membrane receptors, VEGFR1 and VEGFR2, and two soluble receptors, sVEGFR1 and sVEGFR2, which play an antagonistic role. Thus, the objective of this study was to identify the mRNA expression pattern of total VEGF, VEGFR1, VEGFR2, sVEGFR1 and sVEGFR2 in bovine preselected follicles (PRF) and post-selected follicles (POF). The mRNA expression of these five genes in both granulosa cells (GC) and theca cells (TC) was compared between follicles classified as PRF and POF based on their diameter and on their ratio of estradiol/progesterone (E2/P4). Results showed a lower expression of mRNA of sVEGFR1 and sVEGFR2 in POF than in PRF (p < .05). Regarding the mRNA expression of total VEGF, VEGFR1 and VEGFR2, there was no difference between POF and PRF follicles (p > .05). Our results showed that the mRNA expression of VEGFR2 and sVEGFR1 was more abundant than the expression of VEGFR1 and sVEGFR2, while GC was the main source of mRNA for total VEGF. On the other hand, TC was the follicular compartment where the receptors were most expressed. Our results suggest that non-dominant follicles maintain a greater concentration of the mRNA expression of both membrane and soluble VEGF receptors. On the other hand, follicular dominance is related to a reduction in the mRNA expression of sVEGFR1 and sVEGFR2, which may favour VEGF binding with VEGFR2 and, hence, improve the follicular health and development.

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“…In support of this, inhibition of both VEGF [34,35] and KDR [22,31,32,35] has been shown to ameliorate VP development in models of OHSS. In addition, dopamine [36] and [37] dopamine receptor agonists [20,27,38-40] are known inhibit KDR function [36,41] and show promise as both preventative and therapeutic options for OHSS [39,42-45].…”

Section: Introductionmentioning

confidence: 91%

Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome

O’Brien

Harralson

Tran

et al. 2014

Reprod Biol Endocrinol

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BackgroundThe objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).MethodsThis was a case–control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups.ResultsPatients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031).ConclusionsThe KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH.

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Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development

Cited by 103 publications

References 27 publications

Ovarian Folliculogenesis

Ovarian Folliculogenesis

Reduction in the mRNA expression of sVEGFR1 and sVEGFR2 is associated with the selection of dominant follicle in cows

Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome

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