Evidence map›Paper›PMID 38709439›Full record

ArticleScience China. Life sciences2024

DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation.

Yunde Dou, Rusong Zhao, Han Wu, Zhiheng Yu, Changjian Yin, Jie Yang, Chaoyan Yang, Xiaohua Luan, Yixiao Cheng, Tao Huang and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Science China. Life sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

17 authors.

Yunde Dou *Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Rusong Zhao *Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Han WuInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Zhiheng YuInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Changjian YinInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Jie YangInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Chaoyan YangInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Xiaohua LuanInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Yixiao ChengInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Tao HuangInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Yuehong BianInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Shan HanKey laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, 250012, China.
Yuqing ZhangInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Xin XuInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Zi-Jiang ChenInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China.
Han ZhaoInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China. hanzh80@sdu.edu.cn.
Shigang ZhaoInstitute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, China. zsg0108@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs) from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To further explore the functional implications of DENND1A, we generated a transgenic mouse model overexpressing Dennd1a (TG mice). These TG mice exhibited subfertility, irregular estrous cycles, and increased testosterone production following PMSG stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms, thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

Indexed as

Follicle Stimulating HormoneGranulosa CellsGuanine Nucleotide Exchange FactorsMice, TransgenicPolycystic Ovary SyndromeReceptors, FSHAnimalsFemaleHumansMiceProtein TransportTestosteroneFollicle Stimulating HormoneFSHR protein, humanGuanine Nucleotide Exchange FactorsReceptors, FSHTestosteroneDENND1AFSHRovarian granulosa cellsPCOS

Identifiers

PMID38709439

What Socratic 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 Socratic graph.