Embryos sired by males without accessory sex glands induce failure of uterine support: A study of VEGF, MMP and TGF expression in the golden hamster

Abstract

To account for reproductive failure induced by surgical deletion of paternal accessory sex glands in the golden hamster in vivo, we studied expression of vegf, FLT-1 (VEGF-R1), FLK-1 (VEGF-R2), MMP and TGF-β in endometrium of the dam and sired embryos during 5-7 days post coitum by immunohistochemistry, in situ hybridisation, semiquantitative RT-PCR and enzyme-linked immunosorbent assay. Spatiotemporal pattern of vegf expression in the control animals was similar to that reported for intact animals by our group. Removal of paternal ampullary glands did not disturb the normal expression pattern. Removal of ventral prostate glands alone or all accessory sex glands was associated with reduction of vegf transcripts and protein levels in both the embryo and endometrium. FLT-1, FLK-1 and MMP-2 were also reduced. MMP-1 was not changed whereas TGF-β1 expression was enhanced. There was no expression in endometrium in between implantation sites. Thus the implanted embryos had a trophic effect on growth factor production by the endometrium, and the levels of expression were determined by viability and structural integrity of the conceptus. Based on these findings we concluded that incompetent embryos sired by males without the ventral prostate gland or all accessory sex glands reduced the potential of the uterus to support pregnancy. A negative cycle of events was thus set up and eventually led to premature termination of pregnancies.