Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice

Man, Limor; Guahmich, Nicole Lustgarten; Kallinos, Eleni; Park, Laura; Caiazza, Barbara; Khan, M.Z.; Liu, Zong‐Ying; Patel, R; Torres, Carmen de; Lekovich, Jovana P.; Zhong, Liangwen; Bodine, Richard; Wen, Desheng; Zaninović, Nikica; Schattman, Glenn; Rosenwaks, Zev; James, Daylon

doi:10.1016/j.xfss.2021.07.002

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…Hence, increased PAPPA under the AMH condition and augmented bioavailability of IGF ligands may increase signaling and promote accelerated growth and/or maturation. In support of this, we have previously shown in xenografts of ovarian cortical tissue that chronic paracrine expression of exogenous IGF1 increases the pace of follicle growth at preantral stages but accelerates luteinization at antral stages (61). If chronic AMH drives a similar phenotype, then targeted inhibitors of PAPPA that have been developed by multiple groups for limiting IGF bioavailability (62-65) could mitigate this negative influence.…”

Section: Discussionmentioning

confidence: 85%

Chronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts

et al. 2022

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Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and provides a diagnostic measure of reproductive reserve in women; however, the impact of AMH on folliculogenesis is poorly understood. We cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and downstream single-cell RNA sequencing of granulosa and theca/stroma cell fractions. A total of 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals (>10 weeks). In the context of exogenous AMH, follicles exhibited a decreased ratio of primordial to growing follicles and antral follicles of increased diameter. Transcriptomic analysis and immunolabeling revealed a marked increase in factors typically noted at more advanced stages of follicle maturation, with granulosa and theca/stroma cells also displaying molecular hallmarks of luteinization. These results suggest that superphysiologic AMH alone may contribute to ovulatory dysfunction by accelerating maturation and/or luteinization of antral-stage follicles.

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Section: Discussionmentioning

confidence: 85%

Chronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts

et al. 2022

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“…In humans, IGF1R is expressed in GCs of antral follicles and colocalizes with phosphorylated AKT and the FSHR. 88 IGF2 is highly expressed in these cells, but IGF1 is not detectable. 30 , 89 , 90 , 91 , 92 Consequently, the follicular fluid of dominant follicles contains 3‐ to 10‐fold more IGF2 than IGF1.…”

Section: Insulin‐like Growth Factorsmentioning

confidence: 91%

“… 90 However, some reports also found that human GCs and theca cells express the IGF1R. 88 , 122 Moreover, recent single‐cell RNA sequencing data showed that granulosa and theca cells express the IGF1R. 123 Thus, the relative distribution of IGFs and their receptor suggests that autocrine and paracrine IGF actions between GCs, the oocyte, and thecal cells are tightly coordinated during follicle maturation (Figure 5 ).…”

Section: Insulin‐like Growth Factorsmentioning

confidence: 99%

Molecular crosstalk between insulin‐like growth factors and follicle‐stimulating hormone in the regulation of granulosa cell function

Hayes,

Winston,

Stocco

2024

Reprod Medicine & Biology

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BackgroundThe last phase of folliculogenesis is driven by follicle‐stimulating hormone (FSH) and locally produced insulin‐like growth factors (IGFs), both essential for forming preovulatory follicles.MethodsThis review discusses the molecular crosstalk of the FSH and IGF signaling pathways in regulating follicular granulosa cells (GCs) during the antral‐to‐preovulatory phase.Main findingsIGFs were considered co‐gonadotropins since they amplify FSH actions in GCs. However, this view is not compatible with data showing that FSH requires IGFs to stimulate GCs, that FSH renders GCs sensitive to IGFs, and that FSH signaling interacts with factors downstream of AKT to stimulate GCs. New evidence suggests that FSH and IGF signaling pathways intersect at several levels to regulate gene expression and GC function.ConclusionFSH and locally produced IGFs form a positive feedback loop essential for preovulatory follicle formation in all species. Understanding the mechanisms by which FSH and IGFs interact to control GC function will help design new interventions to optimize follicle maturation, perfect treatment of ovulatory defects, improve in vitro fertilization, and develop new contraceptive approaches.

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Effects of in vivo Administration of Insulin-Like Growth Factor-1 on Oocyte and Embryo Development in Mice under Chronic Psychosocial Stress

Igonina,

Lebedeva,

Shavshaeva

et al. 2024

J Evol Biochem Phys

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Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice

Cited by 5 publications

References 52 publications

Chronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts

Chronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts

Molecular crosstalk between insulin‐like growth factors and follicle‐stimulating hormone in the regulation of granulosa cell function

Effects of in vivo Administration of Insulin-Like Growth Factor-1 on Oocyte and Embryo Development in Mice under Chronic Psychosocial Stress

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