A role for the endocannabinoid system in the premature luteal regression and progesterone withdrawal in a LPS-induced early pregnancy loss mode

SCHANDER, J; CORREA, F; BARIANI, MV; BLANCO, J; CYMERYNG, CORA B.; JENSEN, F; WOLFSON, M; FRANCHI, ANA M.

MOLECULAR HUMAN REPRODUCTION.

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2016 vol. 22 p. 800 - 808

1360-9947

Study question: What is the role of the endocannabinoid system (eCS) in thealterations of the endocrine system in a murine model of lipopolysaccharide (LPS)-induced miscarriage?Summary answer: In 7-days pregnant wild type, but not cannabinoid receptor type 1knock-out (CB1-KO) mice, LPS increased COX-2 expression and prostaglandin F2α(PGF2α) production in the uterus leading to lower expression of prolactin receptor in theovary and a marked regression of corpora lutea (CL), suggesting that the eCS mediatesthe deleterious effects of LPS on reproductive events.What is known already: Appropriate systemic progesterone levels are critical for asuccessful pregnancy outcome. Precocious loss of luteal progesterone (P4) secretionleads to miscarriage in rodents. We have previously shown that LPS administration topregnant mice induces embryonic resorption accompanied by a dramatic decrease insystemic progesterone levels in a murine model of inflammatory miscarriage, with theeCS mediating these LPS-induced deleterious effects.Study design, samples/materials, methods: CD1 wild-type (WT) and CB1-KO micewere randomly allocated to Vehicle (saline; i.p.) or LPS (0.5 μg/g body weight; i.p.)treated groups: (WT-Vehicle; WT-LPS; CB1-KO-Vehicle and CB1-KO-LPS). A singleinjection was given on day 7 of pregnancy and tissues (blood, ovary, uterus) werecollected 6, 12, 24 and 48 hours later. P4 and PGF2α plasma levels were determined byradioimmunoassay. Cyclooxygenase-2 (COX-2) mRNA (RT-PCR) and protein(Western blot) content in uterus was assayed. COX-2 and prolactin receptor (PrlR)mRNA levels in the ovary were assayed by RT-PCR. Tissue morphology of the CL wasassessed by haematoxylin-eosin staining. 55Main results and the role of chance: Treatment of 7-day pregnant WT mice with LPSinduced a P4 withdrawal (p