A Multimodal Study of the Relationship Between Exposure to Endocrine Disruptors and Occurrence of Hypospadias - HYPOLLUT

This study aims to demonstrate the impact of Endocrine-Disrupting Chemicals (EDCs) on the risk of hypospadias incidence. It is a multicenter comparative case-control study, involving two groups. The first group consists of biological mothers who have given birth to children with hypospadias (Case Group), while the second group consists of biological mothers who have given birth to children without any malformations (Control Group). Through an integrative approach that combines a direct toxicological study of numerous pollutants present during pregnancy, and a comprehensive exposome assessment using validated tools, this study can significantly enhance our understanding and prevention of this malformation.

Background. Hypospadias is a birth defect of the external genital organs in boys and it ranks the second most common genital malformation in male newborns, following cryptorchidism. Its prevalence is increasing in certain global regions, with an estimated rate of 3.8 cases per 1000 male births. To date, the exact cause of hypospadias remains unknown, however genetic, hormonal, and environmental factors are likely involved. Medical and surgical treatment may be necessary. Furthermore, hypospadias is correlated with fertility issues and is also linked to testicular cancer.

Aim. After ruling out hypospadias with a genetic cause, the aim of this study is to evaluate any significant differences to environmental endocrine disrupting-chemicals (EDCs) exposure between biological mothers of children with hypospadias and those with children without malformation. It aims to demonstrate that this exposure (professional, occupational, environmental) leads to hormonal changes during the neonatal mini-puberty period.

Methods. This research will be conducted as a multicenter case-control study: mother and son with isolated anterior or middle hypospadias (Case Group) and mother and son without hypospadias (Control Group). The clinical investigator plans to enroll 200 patients.

A single visit will be performed. This consultation is part of the usual follow-up for children in the Case Group, while it is specific to the project for children in the Control Group.

During this visit, the investigator:

* will establish the diagnosis of hypospadias (for cases) or absence of genital anomaly (for controls)
* will lead an interview using a questionnaire and a job-exposure matrix to assess EDCs during pregnancy
* will take a hair sample from the mother to measure the substances accumulated during pregnancy
* and finally, will take a blood sample from the child for hormonal evaluation of mini-puberty, and another blood sample from child in the Case Group for analysis and the participation in a DNA collection

Eligibility Criteria:
Non-specific Inclusion Criteria :

* Parents of legal age having signed a free and informed consent for the participation of their child
* Biological mother of a boy aged between 3 and 6 months
* Biological mother with a minimum hair length of 18 cm
* Biological mother who has signed a free and informed consent for her participation
* Biological mother and child affiliated with or beneficiaries of a national health insurance plan
* Biological mother who is fluent in written and spoken French

Specific Inclusion Criteria for Case Group:

- The child has an isolated anterior or middle hypospadias, without any other complex variations of genital development (borderline penile size, unilateral or bilateral cryptorchidism, retractile testes), without malformation syndrome and without identified genetic etiology

Specific Inclusion Criteria for Control Group:

- The child must not present any complex variations in genital development (hypospadias, borderline penis size, unilateral or bilateral cryptorchidism, retractile testes)

Exclusion Criteria:

* Child with another congenital anomaly or malformative syndrome
* Child with an endocrine pathology
* Biological mother or child under legal protection, guardianship, or curatorship
* Biological mother or child in the exclusion period of a previous study
* Biological mother or child included in another clinical study involving a drug

Specific Exclusion Criteria for Case Group:

Biological mother/child pairs if a genetic variant explaining hypospadias is found during genetic analysis.