Identification and Regulation of Bone Morphogenetic Protein Antagonists Associated with Preantral Follicle Development in the Ovary

Fenwick, Mark A.; Mansour, Yosef T.; Hardy, Kate

doi:10.1210/en.2011-0229

Cited by 34 publications

(29 citation statements)

References 63 publications

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“…In this study, the expression of BMP1 was high throughout in vitro culture period and was lightly but significantly affected by E 2 treatment. The functions of various BMPs depend on many BMP antagonists, which are expressed in GCs (Fenwick et al 2011). We detected expression of TWSG1, HTRA1, NBL1, FST, FSTL3, CTGF, CHRD, NOG and GREM1.…”

Section: Rpkm Valuementioning

confidence: 89%

Estradiol supports in vitro development of bovine early antral follicles

Endo¹,

Kawahara-Miki²,

Cao³

et al. 2013

Reproduction

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Antrum formation and estradiol (E 2 ) secretion are specific features of oocyte and granulosa cell complexes (OGCs). This study investigates the effect of E 2 on the in vitro development of bovine OGCs derived from early antral follicles as well as on the expression of genes in granulosa cells (GCs). The supplementation of culture medium with either E 2 or androstenedione (A 4 ) improved the in vitro development of OGCs and the nuclear maturation of enclosed oocytes. When OGCs were cultured in medium containing A 4 , developmentally competent OGCs secreted more E 2 than OGCs that were not competent. In addition, fulvestrant inhibited the effect of both E 2 and A 4 on OGCs development. Comprehensive gene expression analysis using next-generation sequence technology was conducted for the following three types of GCs: i) GCs of OGCs cultured for 4 days with E 2 (1 mg/ml; E 2 (C)), ii) GCs of OGCs cultured for 4 days without E 2 (E 2 (K)) or iii) OGCs that formed clear antrum after 8 days of in vitro culture in medium containing E 2 (1 mg/ml; AF group). GCs of the E 2 (C) group had a similar gene expression profile to the profile reported previously for the in vivo development of large follicles. This genetic profile included factors implicated in the up-regulation of E 2 biosynthesis and down-regulation of cytoskeleton and extracellular matrices. In addition, a novel gene expression profile was found in the AF group. In conclusion, E 2 impacts the gene expression profile of GCs to support the in vitro development of OGCs.Reproduction (2013) 145 85-96

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Section: Rpkm Valuementioning

confidence: 89%

Estradiol supports in vitro development of bovine early antral follicles

Endo¹,

Kawahara-Miki²,

Cao³

et al. 2013

Reproduction

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“…In this study, we chose a single dose of FSH (10 ng/mL) that we had previously shown to be effective in inducing optimal follicle growth (17). Kreeger et al (15) examined dose-related effects of FSH on preantral follicles in a 3-dimensional, alginate-based culture system, but in that study, small and large follicles were grouped together and thus, the influence of initial follicle size on the responsiveness to FSH was not explored.…”

Section: Discussionmentioning

confidence: 99%

“…Whole ovaries were collected from female C57BL/6 mice (Harlan Olac Ltd, Bicester, Oxon, UK) aged between 12 and 21 days postpartum (day of birth = 0 days postpartum), as previously described (17). Mice were housed in accordance with the Animals (Scientific Procedures) Act of 1986 and associated Codes of Practice.…”

Section: Methodsmentioning

confidence: 99%

“…Preantral follicles were mechanically isolated from day 14 to 17 ovaries using 29-gauge insulin needles or acupuncture needles as previously described (17, 26). Follicles were placed in 96 well plates (one ovary per plate) containing α -minimal essential medium (Invitrogen) supplemented with 0.1% (w/v) BSA, 75 µg/mL penicillin, 100 µg/mL streptomycin sulfate, and ITS (5 µg/mL insulin, 5 µg/mL transferrin and 5 ng/mL sodium selenite, Sigma).…”

Section: Methodsmentioning

confidence: 99%

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Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture

et al. 2016

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The obligatory role of follicle-stimulating hormone (FSH) in normal development and function of ovarian antral follicles is well recognized, but its function in preantral growth is less clear. The specific objective of this study was to investigate the response, in culture, to FSH of mouse preantral follicles of increasing size, focusing particularly on growth rate and gene expression. Preantral follicles were mechanically isolated from ovaries of C57BL/6 mice, 12 to 16 days postpartum, and single follicles cultured for up to 96 hours in medium alone (n = 511) or with recombinant human FSH 10 ng/mL (n = 546). Data were grouped according to initial follicle diameter in 6 strata ranging from <100 to >140 μm. Follicles of all sizes grew in the absence of FSH (P < 0.01, paired t test). All follicles grew at a faster rate (P < 0.0001) in the presence of 10 ng/mL FSH but larger follicles showed the greatest change in response to FSH. Even the smallest follicles expressed FSH receptor messenger RNA (mRNA). FSH-induced growth was inhibited by KT5720, an inhibitor of protein kinase A (PKA), implicating the PKA pathway in FSH-induced follicle growth. In response to FSH in vitro, FSH receptor mRNA (measured by quantitative polymerase chain reaction) was reduced (P < 0.01), as was Amh (P < 0.01), whereas expression of StAR (P < 0.0001) and the steroidogenic enzymes Cyp11a1 (P < 0.01) and Cyp19 (P < 0.0001) was increased. These results show heterogeneous responses to FSH according to initial follicle size, smaller follicles being less FSH dependent than larger preantral follicles. These findings strongly suggest that FSH has a physiological role in preantral follicle growth and function.

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“…Because multiple BMPs, along with their signaling receptors, antagonists (e.g., inhibin), and extracellular binding proteins (e.g., gremlin, chordin, and noggin) are widely expressed in different intraovarian compartments, including theca (TCs), granulosa cells (GCs), and ovarian stroma (14)(15)(16)(17)(18), it is likely that BMPs exert autocrine/paracrine actions to regulate follicular steroidogenesis, as well as other aspects of ovarian function (5,8). Our previous findings led us to hypothesize that a functional deficit in thecal BMP signaling could be a contributory factor in the etiology of hyperandrogenemic disorders such as PCOS (13).…”

mentioning

confidence: 99%

Functional link between bone morphogenetic proteins and insulin-like peptide 3 signaling in modulating ovarian androgen production

Glister

Satchell

Bathgate

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Bone morphogenetic proteins (BMPs) are firmly implicated as intraovarian regulators of follicle development and steroidogenesis. Here we report a microarray analysis showing that treatment of cultured bovine theca cells (TC) with BMP6 significantly (>twofold; P < 0.01) up-or down-regulated expression of 445 genes. Insulin-like peptide 3 (INSL3) was the most heavily down-regulated gene (−43-fold) with cytochrome P450, subfamily XVII (CYP17A1) and other key steroidogenic transcripts including steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11, subfamily A1 (CYP11A1) and 3 beta-hydroxysteroid dehydrogenase type 1 (HSD3B1) also downregulated. BMP6 also reduced expression of nuclear receptor subfamily 5A1 (NR5A1) known to target the promoter regions of the aforementioned genes. Real-time PCR confirmed these findings and also revealed a marked reduction in expression of INSL3 receptor, relaxin/insulin-like family peptide receptor 2 (RXFP2). Secretion of INSL3 protein and androstenedione were also suppressed suggesting a functional link between BMP and INSL3 pathways in controlling androgen synthesis. RNAi-mediated knockdown of INSL3 reduced INSL3 mRNA (75%) and protein (94%) level and elicited a 77% reduction in CYP17A1 mRNA and 83% reduction in androstenedione secretion. Knockdown of RXFP2 also reduced CYP17A1 expression (81%) and androstenedione secretion (88%). Conversely, treatment with exogenous (human) INSL3 increased androstenedione secretion ∼twofold. The CYP17A1 inhibitor abiraterone abolished androgen secretion and reduced expression of both INSL3 and RXFP2. Collectively, these findings indicate a positive autoregulatory role for INSL3 signaling in maintaining thecal androgen production, and visa versa. Moreover, BMP6-induced suppression of thecal androgen synthesis may be mediated, at least in part, by reduced INSL3-RXFP2 signaling.growth factor | ovary | reproduction

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Identification and Regulation of Bone Morphogenetic Protein Antagonists Associated with Preantral Follicle Development in the Ovary

Cited by 34 publications

References 63 publications

Estradiol supports in vitro development of bovine early antral follicles

Estradiol supports in vitro development of bovine early antral follicles

Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture

Functional link between bone morphogenetic proteins and insulin-like peptide 3 signaling in modulating ovarian androgen production

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