Characterization of Persistent Organic Pollutants Exposure During Preconception and Preimplantation Development.

Exposure to Environmental Pollution Clinical Trial

— TUBPOP  

Official title:

Characterization of Persistent Organic Pollutants Exposure During Preconception and Preimplantation Development in the Human Fallopian Tube: TUBPOP.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04628091
• Other study ID #: RC31/19/0257
• Secondary ID: RC31/19/0257
• Status: Recruiting
• Phase: N/A
• Start date: January 28, 2021
• Est. completion date: January 2025

Study information

• Verified date: November 2022
• Source: University Hospital, Toulouse
• Contact: Roger LEANDRI, MD
• Phone: 0567771010
• Email: leandri.r[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In order to evaluate if gametes and preimplantation embryos are in vivo exposed to environmental chemicals, the detection of 6 molecules representative of 3 persistent organic pollutants families will be performed in the mucosa of fallopian tubes obtained after bilateral salpingectomy performed for sterilization purpose in 20 women and compared with concentrations in adipose tissue. This feasibility study is a preliminary step before larger clinical surveys and in vitro studies.

Description:

The fallopian tube is the physiological environment of the mature gametes and the preimplantation embryo. While animal and epidemiological data are accumulating that demonstrate the role of alterations of the fetal environment in the programming of post-natal development and health at adulthood, the impact of environmental perturbations during early development (fertilization and preimplantation development) is mainly shown by animal studies (apart persistent questions about health of children conceived after assisted reproductive technologies). Animal expositions to chemical contaminants of the environment targeted on the preimplantation period have been shown to alter health at adulthood. In the same way, in vitro short exposition of male or female gametes to some of these chemicals can impact their functions. It is therefore important to characterize the chemical environment of gametes and preimplantation embryo in the human fallopian tube.

This project aims to demonstrate the feasibility of quantitative measurements for 3 families of persistent environmental contaminants at the oviduct level. In women of reproductive age devoid of any pathology able to alter tubal mucosa, fallopian tubes will be recovered after laparoscopic bilateral salpingectomy performed with the goal of sterilization. Concentrations in the tubal mucosa tissue will be analyzed for at least 2 representative members of 3 chemicals families (organochlorine pesticides (DDE, HCB), polychlorobiphenyls (PCB 153 and 138) and flame retardants (PBDE47 and 153). A comparison with the concentration obtained in the adipose tissue collected at the time of umbilical incision for laparoscopy and in blood will allow to evidence the exposition of each women to each type of contaminant. One bundle of hair strand will be collected from the occipital region of the head and stored for further analysis.

This project is a feasibility study on 20 women but its perspectives are numerous. It is supported by a solid consortium that will assure the recruitment of the women in this indication and its technical implementation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

Inclusion Criteria:

• Addressed to surgery for a voluntary sterilization purpose by bilateral salpingectomy or for total hysterectomy (due to pelvic organs prolapse, functional menorrhagia)

• No previous pathology affecting directly or indirectly the tubal mucosa

• Regular menstrual cycles (26 to 34 days) or under estro-progestative contraceptive

• National health insurance affiliation or equivalent

• Informed and free consent

Exclusion Criteria:

• Absence of 1 or 2 fallopian tubes

• Current or previous disease with persistent effect on tubal mucosa (salpingitis, hydrosalpinx, medically treated extra-uterine pregnancy)

• BRCA1 or 2 mutation in the subject or her first-degree relatives (parents, siblings, children)

• ovarian cancer before age of 50 in a first-degree relative

• uterine, tubal or ovarian anomaly visualized on a presurgical imagery and necessitating a total anatomopathological examination of one of the fallopian tube or a macroscopic anomaly visualized during surgery necessitating a total anatomopathological examination of one of the fallopian tube

• Contraception using progestative alone

• Ovarian desensitisation using gonadotropin-releasing hormone (GnRH) agonists

• Bariatric surgery in the previous year

• Placement under judicial protection, guardianship, or supervision

Related Conditions & MeSH terms

• Exposure to Environmental Pollution

Intervention

Other:
• Sampling on surgery day
In the morning, the day of the surgery (the patient will be fasting): Occipital hair sample (without roots) Venous blood sample (3 tubes of 7mL) During the surgery: Sample of 0.5 to 1 cm3 of subcutaneous adipose tissue during laparoscopic umbilical access Collection of a portion of Ampulla proximal part and Isthmus distal part in order to obtain a piece of approximately 4 cm long (2cm of ampulla and 2 cm of isthmus) for each tube.

Locations

Country	Name	City	State
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

References & Publications (5)

Dereumeaux C, Saoudi A, Pecheux M, Berat B, de Crouy-Chanel P, Zaros C, Brunel S, Delamaire C, le Tertre A, Lefranc A, Vandentorren S, Guldner L. Biomarkers of exposure to environmental contaminants in French pregnant women from the Elfe cohort in 2011. Environ Int. 2016 Dec;97:56-67. doi: 10.1016/j.envint.2016.10.013. Epub 2016 Oct 24. — View Citation

Lee DH, Jacobs DR Jr, Porta M. Hypothesis: a unifying mechanism for nutrition and chemicals as lifelong modulators of DNA hypomethylation. Environ Health Perspect. 2009 Dec;117(12):1799-802. doi: 10.1289/ehp.0900741. Epub 2009 Jul 8. — View Citation

Lee WC, Fisher M, Davis K, Arbuckle TE, Sinha SK. Identification of chemical mixtures to which Canadian pregnant women are exposed: The MIREC Study. Environ Int. 2017 Feb;99:321-330. doi: 10.1016/j.envint.2016.12.015. Epub 2016 Dec 29. — View Citation

Rappaport SM. Genetic Factors Are Not the Major Causes of Chronic Diseases. PLoS One. 2016 Apr 22;11(4):e0154387. doi: 10.1371/journal.pone.0154387. eCollection 2016. — View Citation

Watkins AJ, Fleming TP. Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter. J Anat. 2009 Jul;215(1):52-9. doi: 10.1111/j.1469-7580.2008.01033.x. Epub 2009 Feb 9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects for whom a quantifiable detection for the 6 molecules is obtained	A proportion above or equal to 90 % (quantification in 18 women out of 20 at least) will be the threshold retained as a possible quantification.	During surgery
Secondary	Comparison of intratubal and adipose tissue concentrations of the 6 toxicants	For each of the 6 toxicants, a comparison between the observed intratubal and adipose concentrations will be made within the population and a linear or non-linear relationship will be sought.	During surgery