Evidence map›Paper›PMID 31079267›Full record

ArticleJournal of assisted reproduction and genetics2019

Molecular mechanism of FSHR expression induced by BMP15 in human granulosa cells.

Ken Shimizu, Tomoko Nakamura, Bayasula, Natsuki Nakanishi, Yukiyo Kasahara, Takashi Nagai, Tomohiko Murase, Satoko Osuka, Maki Goto, Akira Iwase and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of assisted reproduction and genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 70 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Ken ShimizuDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Tomoko NakamuraDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. tomonakamura@med.nagoya-u.ac.jp.ORCID http://orcid.org/0000-0001-5987-4384
BayasulaBell Research Center for Reproductive Health and Cancer; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Natsuki NakanishiDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Yukiyo KasaharaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Takashi NagaiDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Tomohiko MuraseDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Satoko OsukaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Maki GotoDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Akira IwaseDepartment of Obstetrics and Gynecology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Japan.
Fumitaka KikkawaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Nagoya University · JPNagoya University Hospital · JPGunma University · JP

Funding

Japan Society for the Promotion of Science 15H04984Japan Society for the Promotion of Science 18K16767
6 · The paper itself

Abstract

purposeFollicle-stimulating hormone receptor (FSHR) expression in granulosa cells is critical in enabling follicles to achieve accelerated growth. Although FSHR expression has been reported to be epigenetically regulated, the mechanism is unclear. Cooperation between oocytes and granulosa cells is also essential for normal follicular growth. Among oocyte-derived factors, bone morphogenetic protein 15 (BMP15) promotes follicular growth and is suggested to have epigenetic effects. We examined the role of BMP15 in the acquirement of FSHR in human granulosa cells.

methodsImmortalized non-luteinized human granulosa (HGrC1) cells were stimulated with trichostatin A (TSA) or BMP15 to analyze FSHR expression, histone modifications, and USF1/2 binding at the FSHR promoter region. Histone acetyl transferase (HAT) activity and phosphorylation of Smad 1/5/8 and p38 MAPK were examined with or without BMP15, SB203580, and LDN193189. CYP19A1 expression and estradiol production were also studied.

resultsTSA and BMP15 induced FSHR mRNA expression in a dose-dependent manner and histone modifications were observed with increased binding of USF1/2. BMP15 increased FSHR protein expression, which was suppressed by LDN193189. BMP15 increased phosphorylation of Smad 1/5/8 and significantly increased HAT activity, which was inhibited by LDN193189, but not by SB203580. BMP15 increased phosphorylation of p38 MAPK and USF1. LDN193189 suppressed BMP15-induced phosphorylation of both p38 MAPK and USF1, whereas SB203580 suppressed the phosphorylation of USF1. BMP15 increased CYP19A1 mRNA expression and estradiol production.

conclusionBMP15 induced FSHR expression in human granulosa cells through Smad and non-Smad pathways. This mechanism of FSHR induction by BMP15 may be utilized for controlling follicular growth.

Indexed as

AromataseBone Morphogenetic Protein 15EstradiolFemaleFollicle Stimulating HormoneGene Expression Regulation, DevelopmentalGranulosa CellsHumansHydroxamic AcidsOocytesOvarian FolliclePyrazolesPyrimidinesReceptors, FSHSignal TransductionSmad ProteinsAromataseBMP15 protein, humanBone Morphogenetic Protein 15CYP19A1 protein, humanEstradiolFollicle Stimulating HormoneFSHR protein, humanHydroxamic AcidsLDN 193189PyrazolesPyrimidinesReceptors, FSHSmad Proteinstrichostatin ABone morphogenetic protein 15Follicle stimulating hormoneGranulosaSmall mothers against decapentaplegic

Identifiers

PMID31079267
PMCPMC6603124
OpenAlexW2944621668

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.