Expression of the endocannabinoid system and response to cannabinoid components by the human fetal testis.

BACKGROUND: Cannabis consumption by pregnant women continues to increase worldwide, raising concerns about adverse effects on fetal growth and deleterious impacts on the newborn, in connection with evidence of placental transfer of cannabis compound. Cannabis action is mediated by the endocannabinoid system (ECS), which expression is well established in the brain but unknown in the developing testis. The fetal testis, whose endocrine function orchestrates the masculinization of many distant organs, is particularly sensitive to disruption by xenobiotics. In this context, we aimed to determine whether cannabis exposure has the potential to directly impact the human fetal testis. METHODS: We determined the expression of components of the ECS in the human fetal testis from 6 to 17 developmental weeks and assessed the direct effects of phytocannabinoids Δ9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the testis morphology and cell functions ex vivo. RESULTS: We demonstrate the presence in the human fetal testis of two key endocannabinoids, 2-arachidonylglycerol (2-AG) and to a lower level anandamide (AEA), as well as a range of enzymes and receptors for the ECS. Ex vivo exposure of first trimester testes to CBD, THC, or CBD/THC [ratio 1:1] at 10-7 to 10-5 M altered testosterone secretion by Leydig cells, AMH secretion by Sertoli cells, and impacted testicular cell proliferation and viability as early as 72 h post-exposure. Transcriptomic analysis on 72 h-exposed fetal testis explants revealed 187 differentially expressed genes (DEGs), including genes involved in steroid synthesis and toxic substance response. Depending on the molecules and testis age, highly deleterious effects of phytocannabinoid exposure were observed on testis tissue after 14 days, including Sertoli and germ cell death. CONCLUSIONS: Our study is the first to evidence the presence of the ECS in the human fetal testis and to highlight the potential adverse effect of cannabis consumption by pregnant women onto the development of the male gonad.

[Value of the health questionnaire in family medicine and hospital consultation]. / Valeur du questionnaire de santé en médecine de famille et en consultation hospitalière.

Questionnaires calling for answers of yes or no were tested in the field of family medicine (125 questions) and in a hospital outpatient clinic (164 questions). In the hospital, results were not given to physicians before evaluation of the patient. In family medicine, 3 328 positive answers were given by 200 patients (average 17), against 3 439 and 115 (average 30) respectively in the hospital. As compared with questionnaires, conventional case-reports missed two out of three symptoms or antecedents, many of which were important. Examples are given. Such omissions were more frequent in males, and in some, specialties. They were not less frequent in common diseases. Unexpectedly, omissions were all the more numerous that patients already had more diagnoses. Filling the questionnaire took an average of 3.5 seconds per question. The opinion of patients was usually favorable. The duration of consultations was slightly increased when using the questionnaires. Questionnaires were useful: to patients, by reducing risks of omissions, fatigue of physicians and disparities between physicians; to physicians, by reducing risks of lawsuits. Economic results are complex. Acceptability is discussed. The initial reluctance of physicians can be overcome. From this experience, the number of questions can be brought down to 89.

[Epidemiology, an accessory application of health questionnaires]. / L'épidémiologie, application accessoire des questionnaires de santé.

Positive answers to health questionnaires, including 3 328 answers by 200 family physician patients and 3 439 answers by 115 hospital outpatients disclosed numerous symptoms, antecedents, and side effects of therapy. Several correlations between findings were detected. Data confirmed previous publications, and may be of use for teaching programs, care organization, and preventive medicine. However, these applications appear as accessory and the main utility of health questionnaires is to help diagnosis in individuals. Should the purpose be epidemiology, questionnaires would become longer as the result of the influence of psychosociologists and experts in data processing. They would only be suitable for polls. In everyday practice, questionnaires will be accepted only if they are kept short.