Abstract
BackgroundEndometrial remodelling is necessary for implantation in all mammalian species. The TGF beta super-family plays a crucial role in this event in humans and mice. However, the role of TGF beta super-family members during implantation is still unclear in ruminants. In the present study, the spacio-temporal expression of TGF beta super-family members including activin was explored in bovine trophoblasts and endometrial tissue during the peri-implantation period in order to elucidate whether it is essential for promoting cell proliferation at the implantation site.MethodsGene expression in the fetal membrane and endometrium of the gravid and non-gravid horn around Day 35 of gestation were analyzed with a custom-made oligo-microarray in cattle. The expression of activin and its related genes was also analyzed with quantitative RT-PCR. Activin-like activity in trophoblastic tissue and BT-1 cells was examined using a fibroblast cell proliferation test and Western blotting.ResultsThe expression of various TGF beta super-family related genes including activin was detected in trophoblasts and the endometrium in cattle. The most intensive activin expression was found in the gravid horn endometrium, and rather intense expression was detected in the non-gravid trophoblastic tissue. Extracts from the fetal membrane including trophoblasts and purified activin both stimulated fibroblast proliferation effectively, and activin was immunologically detected in BT-1 cells, which have trophoblastic features.ConclusionsSpecific expression of the activin gene (gene name: inhibin beta A) was found in the gravid horn endometrium during peri-implantation. An activin-like molecule, which was derived from the endometrium and trophoblasts, stimulated the proliferation of fibroblast cells. These results suggested that as in other species, the activity of TGF beta super-family members including activin-like molecules plays a pivotal role in endometrial remodelling, which is an essential process in implantation and placentogenesis during the peri-implantation period in cattle.
Highlights
Endometrial remodelling is necessary for implantation in all mammalian species
Gene expression levels of TGFb super-family members in the fetal membrane and endometrium during implantation Around Day 35 of gestation, no placentomal villi, which were identified as spots with fine capillaries, were found in the FM in the non-gravid horn (NGH), and less than 30 villi were macromorphologically confirmed in the FM in the gravid horn (GH)
In FM, activin-related genes like inhibin alpha (INHA), INHbA, INHbB, FST, transforming growth factor beta 1 (TGFb1), and heparinbinding epidermal growth factor (HB-EGF) were detectable in both the GH and the NGH; fibroblast growth factor 2 (FGF2) was not detectable (Tables 3, 4)
Summary
Endometrial remodelling is necessary for implantation in all mammalian species. The TGF beta superfamily plays a crucial role in this event in humans and mice. The cells from the fetus and mother only fuse and develop into the placentome in a limited area, namely the caruncle (CAR) on the endometrium in [6] may play an important role at this site in cattle, and the fusion of trophoblast and endometrial epithelial cells starts around 20 days of gestation [7,8,9]. These phenomena have been morphologically confirmed, the detailed mechanisms behind them are still unclear in ruminants. These growth factors may affect the initiation of endometrial proliferation during implantation in these species
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