Fibroblast growth factor-2 expression in the preimplantation equine conceptus and endometrium of pregnant and cyclic mares.
Abstract: Uterine-derived growth factors and cytokines play essential roles in regulating preimplantation conceptus development. In several species, fibroblast growth factor-2 (FGF2) promotes embryogenesis, trophoblast cell migration, and adhesion. This study investigated mRNA expression for FGF2, its receptors (FGFR1-4), the activating factor FGF binding protein (FGF-BP) in equine endometrium and trophectoderm during early pregnancy and the estrous cycle, and localized FGF2 protein in both endometrium and conceptus tissues. FGF2, FGFRs1-4, and FGFBP mRNAs were expressed in endometrium throughout the estrous cycle and early pregnancy, and in days 14 to 28 conceptus membranes. FGF2 transcription was higher during estrus than on days 7 or 14 of diestrus, suggesting estrogen dependency. Endometrial expression of FGF2 mRNA and protein increased as pregnancy progressed from days 21 and day 28; FGF2 protein was localized predominantly in the luminal and glandular epithelium. FGF2 mRNA was detectable in trophectoderm from as early as day 14, and transcription and translation increased in day 21 and 28 allantochorion. FGF2 protein was localized mainly in the trophectoderm up to day 21 but was present in both trophectoderm and endoderm of day 28 allantochorion. FGFR1 mRNA was down-regulated in the endometrium at day 7 of diestrus but increased again by day 14. Gene expression for all of the FGFR2 splice variants, including FGFR2IIIc, was up-regulated during estrus. During early pregnancy, endometrial FGFR1 expression decreased, whereas FGFR2IIIc expression did not change. Conceptus mRNA expression for all FGFRs increased as pregnancy progressed. FGFBP expression remained unchanged in endometrium, but increased in the conceptus between days 14 and 28, suggesting a role in regulating FGF2 activity in the developing conceptus. We conclude that during weeks 3 and 4 of pregnancy, the equine endometrial epithelium produces FGF2, which may play a role in trophoblast development and adhesion.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication Date: 2013-09-12 PubMed ID: 24035195DOI: 10.1016/j.theriogenology.2013.07.024Google Scholar: Lookup
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Summary
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This study looks into the roles of uterine-derived fibroblast growth factor-2 (FGF2) in the development of the conceptus (embryo and surrounding tissues) in horses during early pregnancy and the estrous cycle. The researchers found that FGF2 and its receptors, as well as the activating factor FGF binding protein, were expressed in the equine endometrium and the embryo’s trophectoderm throughout these periods, suggesting a possible role in trophoblast development and adhesion.
Understanding the Role of FGF2
- This research investigates the expression of fibroblast growth factor-2 (FGF2) and its receptors in the endometrium and trophectoderm of mares during early pregnancy and the estrous cycle.
- FGF2 is known to promote embryogenesis, trophoblast cell migration, and adhesion in several species. Trophoblast cell migration and adhesion are crucial steps in the establishment of pregnancy.
- The study showed that FGF2 and its receptors are present in both the endometrium (the inner lining of the uterus) and the trophectoderm (the cell layer that forms contact with the endometrium and develops into the placenta) from day 14 to day 28 of the gestation period.
FGF2 Expression in Endometrium and Trophectoderm
- The researchers noted that the level of FGF2 expression in the endometrium was higher during estrus than on days 7 or 14 of diestrus, indicating estrogen dependency.
- Both the transcript and protein of FGF2 in the endometrium were noted to increase as pregnancy progressed from day 21 to day 28, with FGF2 protein predominantly localized in the luminal and glandular epithelium.
- FGF2 mRNA was detectable in trophectoderm as early as day 14, and there were increases in transcripts and translation on day 21 and 28 of pregnancy.
Expression of FGF2 Receptors and Activating Factor
- In terms of FGF2 receptors (FGFR1-4), the study found that FGFR1 mRNA was down-regulated in the endometrium at day 7 of diestrus but increased again by day 14. During early pregnancy, endometrial FGFR1 expression decreased while FGFR2IIIc expression did not change.
- The researchers observed that the expression of all FGFRs in the conceptus increased as pregnancy progressed.
- As for the expression of FGF binding protein (FGF-BP) – the activating factor of FGF2 – it remained constant in the endometrium throughout the observed period but saw an increase in the conceptus between days 14 and 28, suggesting a specific role in regulating FGF2 activity in the developing embryo.
Implications of the Study
- The findings suggest that the equine endometrial epithelium produces FGF2 during weeks 3 and 4 of pregnancy, which may contribute to trophoblast development and adhesion – a crucial step in establishing successful pregnancy.
- They also provide hints at the possible estrogen dependency of FGF2 expression and its roles at different stages of the estrous cycle and early pregnancy, which may feed into the broader understanding of the reproductive process in horses.
Cite This Article
APA
de Ruijter-Villani M, van Boxtel PR, Stout TA.
(2013).
Fibroblast growth factor-2 expression in the preimplantation equine conceptus and endometrium of pregnant and cyclic mares.
Theriogenology, 80(9), 979-989.
https://doi.org/10.1016/j.theriogenology.2013.07.024 Publication
Researcher Affiliations
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. Electronic address: m.villani@uu.nl.
MeSH Terms
- Animals
- Blastocyst / metabolism
- Cell Adhesion
- Embryo Implantation
- Embryonic Development
- Endometrium / metabolism
- Estrous Cycle / metabolism
- Female
- Fibroblast Growth Factor 2 / metabolism
- Horses / embryology
- Immunohistochemistry
- Pregnancy
- Pregnancy, Animal / metabolism
- RNA, Messenger / metabolism
- Receptor, Fibroblast Growth Factor, Type 1 / metabolism
- Receptor, Fibroblast Growth Factor, Type 2 / metabolism
- Receptor, Fibroblast Growth Factor, Type 3 / metabolism
- Receptor, Fibroblast Growth Factor, Type 4 / metabolism
Citations
This article has been cited 11 times.- Siemieniuch-Tartanus M. The early pregnancy in mares - What do we still not know?. Vet Anim Sci 2025 Jun;28:100441.
- Ahmadi K, Reiisi S, Habibi Z. Comparison of the gene expression profiles of endometrial and trophoblastic cells in women with recurrent miscarriage: A bioinformatics approach. Int J Reprod Biomed 2024 Jun;22(6):495-506.
- Kharamani A, Mashayekhi F, Salehi Z. Association of Fibroblast Growth Factor-1 Promoter Polymorphism and its Serum Concentrations with Repeated Implantation Failure after In vitro Fertilisation: A Cross-sectional Study. J Hum Reprod Sci 2024 Apr-Jun;17(2):121-127.
- Bazer FW, Johnson GA. Early Embryonic Development in Agriculturally Important Species. Animals (Basel) 2024 Jun 26;14(13).
- Noghrehalipour N, Aflatoonian R, Rahimipour A, Aghajanpour S, Najafian A, Chekini Z, Ghaffari F, Kazerouni F. The Effect of Altered Mucin1, FGF2, and HBEGF Gene Expression at The Ectopic Implantation Site and Endometrial Tissues in The Tubal Pregnancy Pathogenesis: A Case-Control Study. Int J Fertil Steril 2023 Aug 7;17(4):242-247.
- D' Fonseca NMM, Gibson CME, van Doorn DA, Roelfsema E, de Ruijter-Villani M, Stout TAE. Effect of Overfeeding Shetland Pony Mares on Embryonic Glucose and Lipid Accumulation, and Expression of Imprinted Genes. Animals (Basel) 2021 Aug 26;11(9).
- Rizzo M, Stout TAE, Cristarella S, Quartuccio M, Kops GJPL, De Ruijter-Villani M. Compromised MPS1 Activity Induces Multipolar Spindle Formation in Oocytes From Aged Mares: Establishing the Horse as a Natural Animal Model to Study Age-Induced Oocyte Meiotic Spindle Instability. Front Cell Dev Biol 2021;9:657366.
- Gibson C, de Ruijter-Villani M, Bauersachs S, Stout TAE. Asynchronous Embryo Transfer Followed by Comparative Transcriptomic Analysis of Conceptus Membranes and Endometrium Identifies Processes Important to the Establishment of Equine Pregnancy. Int J Mol Sci 2020 Apr 7;21(7).
- Bonometti S, Menarim BC, Reinholt BM, Ealy AD, Johnson SE. Growth factor modulation of equine trophoblast mitosis and prostaglandin gene expression. J Anim Sci 2019 Feb 1;97(2):865-873.
- Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, de Mestre AM. Dynamic changes in gene expression and signalling during trophoblast development in the horse. Reproduction 2018 Oct 1;156(4):313-330.
- Tachibana Y, Sakurai T, Bai H, Shiota K, Nambo Y, Nagaoka K, Imakawa K. RNA-seq analysis of equine conceptus transcripts during embryo fixation and capsule disappearance. PLoS One 2014;9(12):e114414.
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