Hormonal interactions in the control of granulosa cell differentiation

Dorrington, Jennifer H.; McKERACHER, Heather; Chan, Agnes; Gore-Langton, Robert E.

doi:10.1016/s0022-4731(83)80003-x

Cited by 42 publications

(7 citation statements)

References 73 publications

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“…This indicates that follicles that pass the developmental ‘block’ are more likely to survive, potentially due to decreased competition. Increased follicle survival may also be linked to the increased FSH levels (Williams & Stanley 2011), which promotes the survival of developing follicles (Dorrington et al 1983). Oocyte-specific factors are also known to play a role in apoptosis and we have recently shown that ovaries generating oocytes devoid of core 1 O -glycans have a higher expression ratio of GDF9:BMP15 accompanied with reduced apoptosis (Williams & Stanley 2008, Grasa et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of follicle development in a mouse model of premature ovarian insufficiency

Grasa¹,

Sheikh²,

Krzys³

et al. 2016

Reproduction

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Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age. In this study we investigate the cause of the reduced fertility at 6 weeks and infertility at 9 weeks of DM females. Ovary sections were used to analyse follicle and corpora lutea (CL) numbers, apoptosis, and levels of laminin and 3β-hydroxysteroid dehydrogenase using immunohistochemistry. After POI, DM females unexpectedly remained sexually receptive. At both 6 and 9 weeks, DM ovaries contained more primary follicles, however, at 9 weeks DM follicles were proportionally healthier, revealed by TUNEL analysis compared with Controls. In 9 week DM ovaries (collected post-mating), secondary follicles had theca and basal lamina structure abnormalities, whilst preovulatory follicles failed to ovulate resulting in the presence of numerous luteinised unruptured follicles, indicative of ovulation failure. Finally, DM ovaries contained more regressing CL with decreased luteal cell apoptosis indicative of a defect in CL regression. Identifying these follicular modifications have provided insight into the aetiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of follicle development in a mouse model of premature ovarian insufficiency

Grasa¹,

Sheikh²,

Krzys³

et al. 2016

Reproduction

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“…During the transition from a preantral to an antral stage, follicles are highly susceptible to atresia, and FSH can be considered a survival factor (59,60). This transition is a critical point and unless follicles are provided with the FSH they require, they will undergo atresia (59,61).…”

Section: Discussionmentioning

confidence: 99%

Oocytes lacking O ‐glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression

2014

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The number of eggs ovulated varies within and between species and is influenced by many variables. However, the regulatory mechanisms remain poorly understood. We previously demonstrated a key role for the oocyte because mice generating oocytes deficient in core 1-derived O-glycans ovulate ∼40-50% more eggs than Controls. Here we analyze the basis of this phenotype using Mutant [core 1 β1,3-galactosyltransferase 1 (C1galt1)(FF):zona pellucida glycoprotein 3 Cre (ZP3Cre)] and Control (C1galt1(FF)) female mice. In culture, Mutant follicles exhibited delayed antrum formation [indicative of follicle stimulant hormone (FSH) dependence] and increased sensitivity to FSH. Although the Mutant estrous cycle was extended, comprehensive endocrine changes were not observed; rather FSH, LH, inhibin B, and anti-Mullerian hormone were temporally altered, revealing estrous cycle stage-specific modifications to the hypothalamic-pituitary-gonadal axis. At proestrus, when FSH levels were decreased in Mutants, ovaries contained more, smaller, preantral follicles. Mutant follicles exhibited reduced levels of apoptosis, and both B-cell lymphoma 2 (Bcl-2) and BCL-2-associated X protein (Bax) were altered compared with Controls. Mutant ovaries also had an increase in the expression ratio of growth differentiation factor 9 (GDF9):bone morphogenetic protein 15 (BMP15) at diestrus. On the basis of these data, we propose that modified oocyte glycoproteins alter GDF9:BMP15 expression modifying follicle development resulting in the generation of more follicles. Thus, the oocyte is a key regulator of follicle development and has a crucial role in determining ovulation rate.

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“…We used PMSG-treated rat granulosa cells as antigen for the following reasons: 1) granulosa cells comprise the major cell type in the ovary of PMSG-treated rats; 2) t, he granulosa cells preparation used in the present study has previously been shown to have a low percentage of contaminant cell types [6]; 3) in spite of the small size of the immature rat ovary it is feasible to derive sufficient quantities of granulosa cells to generate the amount of conditioned medium required for the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Immature female 25-day-old Wistar rats were injected with 8 IU of pregnant mare serum gonadotropin (PMSG) (Gestil, Organon, Oss, the Netherlands) and killed 48 h after treatment. Granulosa cells were recovered from the ovaries with a fine needie [6] and were plated in Dulbecco's modified Eagle's medium (DMEM) supplemented with 50 U/ml penicillin, 50/zg/ml streptomycin and 5070 (v/v) foetal calf serum (FCS). The cells were cultured at 37°C in a humidified atmosphere of 5070 CO2 in air.…”

Section: Cell Culture and Medium Collectionmentioning

confidence: 99%

Localization and partial characterization of a rat ovarian granulose cell protein with a monoclonal antibody

Russinova

Vassilev

Davidoff

1993

Biology of the Cell

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Hybridoma cell lines were obtained from mouse splenocytes sensitized to granulosa cells collected from rat ovaries after gonadotropin stimulation. A monoclonal antibody (5G5) was obtained which reacted with granulosa cells and showed a positive reaction with serum-free conditioned medium containing granulosa cell secreted proteins. Immunoblotting of the conditioned medium and light- and electron-microscopic immunocytochemistry of rat ovary show that mAb 5G5 is directed against a 59-kDa protein which is located on the plasma membrane of granulosa cells. Furthermore, the immunoreactivity of the granulosa cells depends both on the degree of follicle development and on the position of the granulosa cells within the follicles. Strong immunoreactivity was observed in the innermost granulosa cell layers, close to the oocyte and the antral cavity. The results obtained show that mAb 5G5 is a useful marker of a 59-kDa granulosa cell protein which might be of importance for the development of the follicle and the oocyte maturation.

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Hormonal interactions in the control of granulosa cell differentiation

Cited by 42 publications

References 73 publications

Dysregulation of follicle development in a mouse model of premature ovarian insufficiency

Dysregulation of follicle development in a mouse model of premature ovarian insufficiency

Oocytes lacking O ‐glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression

Localization and partial characterization of a rat ovarian granulose cell protein with a monoclonal antibody

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