Crosstalk between uterine serpin (SERPINA14) and pregnancy-associated glycoproteins at the fetal-maternal interface in pregnant dairy heifers experimentally infected with Neospora caninum

Abstract

Infection with Neospora caninum is the leading cause of abortion in cattle. In cows naturally infected with N caninum, plasma concentrations of pregnancy-associated glycoproteins (PAG) 1 and 2 indicate fetal-placental well-being, whereas an excess of progesterone in the second trimester of gestation has been related to high abortion rate. The immunosuppressive action of progesterone on the uterus during gestation has been attributed in part to the uterine serpins (SERPINA14). This study examines expression patterns of the genes SERPINA14, PAG, and PAG2 at the fetal-maternal interface in dairy heifers experimentally infected with N caninum during the second trimester of pregnancy, when most abortions takes place in natural conditions. Irrespective of infection, expression of SERPINAI4 was higher, and expression of PAG1 and PAG2 lower, for intercaruncular endometrium than for caruncles or cotyledons. Cotyledonary tissues showed the highest expression of both PAG genes but lowest expression of SERPINAI4. The expression of SERPINAI4 was significantly higher in intercaruncular endometrium of control dams than for infected animals, pointing to potential disruption of modulation of maternal immune function during infection. Dramatically reduced SERPINAI4 was particularly apparent in infected dams with aborted fetuses. There was also a negative association between N caninum antibody titers with SERPINAI4 and PAG expression in infected animals, further suggesting that N caninum infection downregulates the uterine immunosuppressive function of SERPINAI4.

This study was supported by a grant from the Spanish MINECO (AGL2012-39830-C02-01/02) and FEDER. Ramón Mur-Novales was awarded an FPI grant by the Spanish Ministry of Science and Innovation, MICINN, BES-2013-063215. The authors thank Ana Burton for editorial assistance, the farmers who provided the experimental animals and the staff of CReSA for their help with managing the animals, and Dr. L.M. Ortega-Mora (SALUVET, Universidad Complutense, Madrid, Spain), for the Neospora isolate.