P-600 cannabinoids exposure during pregnancy affects female offsprings reproduction

Abstract Study question Could in-utero exposure to cannabinoids alter the reproductive health of female offspring? Summary answer Prenatal causes a reduction ovarian reserve in F1 with compromised lifespan and low birth weight F1/ F2 generations. What is known already Cannabis use during pregnancy associated adverse neonatal outcomes: preterm birth, intrauterine growth retardation, weight, neurological developmental changes. However, impact on germ line still little known. Cannabis/cannabinoids exert their biological effect by activating two main cannabinoid receptors: CB1 CB2. We previously demonstrated that fetal oocytes express CB2 receptors at higher level than CB1. In vitro treatment JWH-133, selective agonist, induces an acceleration meiosis increase percentage γ-H2AX-positive cells TUNEL-positive (apoptotic cells). design, size, duration Five pregnant CD1 mice were intraperitoneally injected single dose 1.5 mg/kg for 5 days between embryonic period (E) 12.5 E16.5, while control females received vehicle containing saline. At delivery, post-natal day (PND) 2, 30 365, pups counted, weighted tissues from collected. adult age, mated generation was morphologically analysed. Participants/materials, setting, methods Ovaries utero exposed fixed paraformaldehyde stained Haematoxylin Eosin (H&E). Gonads embedded paraplast sectioned 5μm Leica-RM 2035 Microtome. Follicles each ovary counted serially every third section through entire ovary. Only healthy, non-atretic follicles visible oocyte nuclei scored. Main results role chance demonstrate vivo JWH-133 life, administration drug females, significant offspring body (LBW). Histological analysis ovaries isolated newborn (PND2) shows primordial primary follicles. This reduced observed also PND30 PND365. old these crossed males, show drastic decrease litter size (F2) across life course comparison females. suggests pool becomes prematurely depleted compromising lifespan. Moreover, we find prenatally mothers LBW but have unaltered number Since never been drug, our suggest transmitted mother intergenerationally, consequence direct it not generation. Limitations, reasons caution The effects cannot be directly translated cannabis since active principle (THC) activates both receptors. this study lacks molecular gene expression implicated intergenerational transmission. Wider implications findings first demonstration prenatal could long-term critical consequences females’ health. humans, diminished characterized poor fertility outcomes represents major challenge medicine. Trial registration applicable