Battle of sex hormones in genitalia anomalies

Ma, Liang

doi:10.1073/pnas.1518491112

Cited by 2 publications

(2 citation statements)

References 17 publications

(15 reference statements)

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“…In addition to their effect on beta-catenin signaling, sex steroids regulate differentiation of the genital tubercle into the male penis. Hormonal disruptions during penile development can cause urethral and epithelial abnormalities that result in hypospadias and chordee 37,38 . The cytochrome P450 superfamily of enzymes are responsible for catalyzing the synthesis of sex steroids from cholesterol, fatty acids, and other lipids.…”

Section: Discussionmentioning

confidence: 99%

Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias

Richard

Sok

Canon

et al. 2020

Sci Rep

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Hypospadias is a common birth defect where the urethral opening forms on the ventral side of the penis. We performed integrative methylomic, genomic, and transcriptomic analyses to characterize sites of DNA methylation that influence genital development. In case-control and case-only epigenome-wide association studies (EWAS) of preputial tissue we identified 25 CpGs associated with hypospadias characteristics and used one-sample two stage least squares Mendelian randomization (2SLS MR) to show a causal relationship for 21 of the CpGs. The largest difference was 15.7% lower beta-value at cg14436889 among hypospadias cases than controls (EWAS P = 5.4e−7) and is likely causal (2SLS MR P = 9.8e−15). Integrative annotation using two-sample Mendelian randomization of these methylation regions highlight potentially causal roles of genes involved in germ layer differentiation (WDHD1, DNM1L, TULP3), beta-catenin signaling (PKP2, UBE2R2, TNKS), androgens (CYP4A11,

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Section: Discussionmentioning

confidence: 99%

Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias

Richard

Sok

Canon

et al. 2020

Sci Rep

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“…Environmental exposures with endocrine disrupting capabilities are hypothesized to play a role in the occurrence of hypospadias [ 28 , 29 ]. Given that hormones are critical in the masculinization of the external genitalia during male fetal development [ 30 ], it is hypothesized that exogenous exposures that interfere with androgen or estrogen pathways may partially explain malformations of the male urethra [ 31 , 32 ]. Several animal models support this notion and have demonstrated that exposure to endocrine disrupting chemicals can induce hypospadias in experimental settings [ 17 , 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal Exposure to Disinfection By-Products and Risk of Hypospadias in the National Birth Defects Prevention Study (2000–2005)

Ibrahim

Luben

Desrosiers

et al. 2020

IJERPH

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The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water-use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias.

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Battle of sex hormones in genitalia anomalies

Cited by 2 publications

References 17 publications

Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias

Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias

Maternal Exposure to Disinfection By-Products and Risk of Hypospadias in the National Birth Defects Prevention Study (2000–2005)

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