Evidence map›Paper›PMID 38563741›Full record

ArticleAsian journal of andrology2024

The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.

Yu Ding, Zu-Quan Chen, Wen-Feng Pan, Hao-Jie Chen, Min Wu, Yi-Qing Lyu, Hua Xie, Yi-Chen Huang, Zhong-Zhong Chen, Fang Chen

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Asian journal of andrology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
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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

10 authors at 2 institutions in 1 country.

Yu DingDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Zu-Quan ChenDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Wen-Feng PanDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Hao-Jie ChenDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Min WuDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Yi-Qing LyuDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Hua XieDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Yi-Chen HuangDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Zhong-Zhong ChenDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Fang ChenDepartment of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Shanghai Jiao Tong University · CNShanghai Children's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias ( P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [ DNAH8 ]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a ( Wnt5a ), Wnt5b , Smad family member 2 ( Smad2 ), and Smad3 ; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase ( AMPK ) and nuclear respiratory factor 1 ( Nrf-1 ); and vascular development-related genes such as myosin light chain ( MLC ), notch receptor 3 ( Notch3 ), and sphingosine kinase 1 ( Sphk1 ), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Indexed as

FingersHypospadiasAnimalsCase-Control StudiesChildChild, PreschoolFemaleHumansMaleMicePregnancyReceptors, AndrogenTestosteroneReceptors, AndrogenTestosterone

Identifiers

PMID38563741
PMCPMC11280205
OpenAlexW4393494446

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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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.