Effects of catecholaminergic nerve lesion on endometrial development during early pregnancy in mice

Abstract

Maternal stress is common during pregnancy and the postnatal period. This stress typically activates the sympathetic nervous system which releases catecholamines. This study explored the influence of sympathectomy by using neurotoxin 6-hydroxydopamine (6-OHDA) on embryo implantation, and investigated the influence mechanism of sympathectomy on reconstruction of endometrial structure during early pregnancy. In the 6-OHDA-treated mice, uterine glands in the endometrium developed poorly, and the gland epithelia were arranged irregularly during early pregnancy. Furthermore, vacuoles, karyopykosis and plasmarrhexis appeared in some gland epithelia. The percentage of uterine glands and the density of proliferating cell nuclear antigen (PCNA) positivity were dramatically decreased, and Fas ligand (FasL) expression was decreased in cells from pregnancy days 5-9 (E5-9) in the treated group. Antioxidant enzyme activity levels in uteri were lower but the malondialdehyde (MDA) levels were higher in the 6- OHDA mice than those in the control mice at E5-9. Similarly, the number of inducible nitric oxide synthase (iNOS) positive cells was significantly increased during early pregnancy following treatment with 6-OHDA. Our results have indicated that peripheral catecholaminergic nerve lesions induced by 6-OHDA cause adverse pregnancy outcomes through disruption of endometrial gland development, which increases oxidative stress and iNOS expression in the endometrium. Thus, catecholaminergic nerves might favourably influence blastocyst implantation, foetal survival and development during early pregnancy by oxidative state regulation and endometrial gland reconstruction.