| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
RESEARCH |
Department of Animal Science, Oklahoma Agricultural Experiment Station, Animal Science Building, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Correspondence should be addressed to R Geisert; Email: Rodney.Geisert{at}okstate.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
Implantation of pig conceptuses involves a superficial attachment of the trophoblast to the microvilli located on the uterine apical surface epithelium between Days 13 and 18 of gestation (Dantzer 1985). Trophoblast attachment to the uterine lumenal surface epithelium is mediated by a number of endometrial cytokines, growth factors, and interactions between the developing conceptus and apical expression of endometrial integrins on the surface epithelium (Burghardt et al. 1997, Geisert & Yelich 1997). The IGF system has been characterized in a multitude of biological systems (Simmen et al. 1992, Irwin et al. 2001, Sato et al. 2002) and is composed of three ligands (IGF-I, IGF-II, and insulin), five or more regulatory binding proteins (IGFBP-1 through -6), and three or more cell surface receptors (IGF type I and II receptors, insulin receptor, and hybrid receptors) (Jones & Clemmons 1995, Butler & LeRoith 2001). The porcine conceptus has been reported to express mRNA for IGF type I receptor (IGF-IR) (Corps et al. 1990). Although gene expression for IGF-IR was demonstrated, Chastant et al.(1994) were unable to detect the presence of IGF-IR in the trophoblast, but did immunolocalize IGF type II receptor (IGF-IIR). Conceptus expression of the IGF-IR mRNA and the presence of trophoblast IGF-RII indicate that uterine IGF secretion could serve an integral part in early porcine conceptus development and survival.
The importance of IGFs in early porcine conceptus development and uterine receptivity for implantation is demonstrated by the precise alteration in the presence of IGFBPs that occur during the period of conceptus expansion (Lee et al. 1998, Geisert et al. 2001). Uterine IGFBPs are present in the porcine uterine lumen from Day 5 to Day 10 of the oestrous cycle and during early gestation (Lee et al. 1998, Geisert et al. 2001). However, the porcine uterine lumenal IGFBPs are proteolytically cleaved after Day 11 in both cyclic and pregnant gilts. Activation of proteolytic enzymes such as serine protease, tissue kallikrein and the matrix metalloproteinases degrade IGFBPs in the uterine lumen allowing IGF stimulation of the conceptuses during a critical period of development in the pig (Lee et al. 1998, Geisert et al. 2001).
Our laboratory has established that conceptus secretion of oestrogen between Days 11 and 13 of gestation plays a critical role in the normal process of implantation in pigs, and we have demonstrated that oestrogen can function as an endocrine disruptor of implantation if administered on Days 9 and 10, i.e. 48 h prior to the normal period of secretion of oestrogen and 96 h prior to initiation of implantation. Exposure of pregnant gilts to exogenous oestrogens before the normal physiological secretion of conceptus oestrogens on Day 12 results in complete embryonic mortality before Day 30 of gestation (Pope et al. 1986). Early exposure of gilts to oestrogen on Days 9 and 10 of pregnancy causes conceptus degeneration and fragmentation between Days 15 to 18 of gestation (Gries et al. 1989, Blair et al. 1991). Recently, the concentration and timing of oestrogen stimulation was demonstrated to function within a very narrow range to open the window for uterine receptivity in the mouse (Ma et al. 2003). High concentrations of oestrogen shorten the window of receptivity and cause implantation failure as a result of aberrant uterine gene expression during blastocyst attachment. We propose that oestrogen treatment of pregnant gilts on Days 9 and 10 alters the timing of the presence of IGF-I within the uterine lumen, which could be critical for continued embryonic development.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
Surgical procedure
Bred gilts were hysterectomized through a midventral laparotomy on Days 10, 12, 13, 15 or 17 of gestation as previously described by Gries et al.(1989). Following initial induction of anaesthesia with a 1.8 ml i.m. administration of a cocktail consisting of 2.5 ml Xylazine (100 mg/ml; Miles Inc., Shawnee Mission, KS, USA) and 2.5 ml Vetamine (Ketamine HCl, 100 mg/ml; Molli Krodt Veterinary, Mundelein, IL, USA) in 500 mg Telazol (Tiletamine HCl and Zolazepum HCl; Fort Dodge, Syracuse, NE, USA), anaesthesia was maintained with a closed circuit system of halothane (5% flurothane) and oxygen (1.0 l/min). Uteri were exposed via a midventral laparotomy and a randomly selected uterine horn and its ipsilateral ovary were excised. Uterine lumenal contents and conceptuses were flushed from the horn by infusing 20 ml phosphate buffered saline (PBS, pH 7.4) through the lumen and collecting the flushings into a Petri dish. Conceptuses were removed from the flushings, snap frozen in liquid nitrogen and stored at –80 °C. Uterine flushings were centrifuged at 1000 g for 10 min at 4 °C, the supernant was collected and was stored at –20 °C. Endometrial tissue was removed from the antimesometrial side of the uterine horn, immediately snap frozen in liquid nitrogen and stored at –80 °C until utilized for RNA extraction.
Endometrial RNA extraction
Total RNA was extracted from endometrial tissue using RNAwiz reagent (Ambion, Inc., Austin, TX, USA). Approximately 0.5 g endometrial tissue was homogenized in 5.0 ml RNAwiz using a Virtishear homogenizer (Virtis Company Inc., Gardiner, NY, USA). RNA was rehydrated in nuclease-free water and stored at –80 °C. Total RNA was quantified with a spectrophotometer at an absorbance of 260 nm and purity was verified based on the 260/280 ratio.
Quantitative one-step reverse transcription-polymerase chain reaction (RT-PCR)
Quantitative analyses of endometrial IGF-I and IGF-IR mRNA were conducted using quantitative real-time RT-PCR as previously described (Hettinger et al. 2001). The PCR amplification was performed in a reaction volume of 15 µl using an ABI PRISM 7700 Sequence Detection System (PE Applied Biosystems, Foster City, CA, USA). The transcripts were evaluated using dual labelled probes containing 6-Fam (5' reporter dye), and TAMRA (3' quenching dye). Primer and probe sequences for the amplification of IGF-I and IGF-1R (Table 1
) were generated from porcine cDNA sequences available in the NCBI database. Total RNA (100 ng) was assayed in duplicate using thermocycling conditions for one-step cDNA synthesis of 30 min at 48 °C and 95 °C for 10 min, followed by 45 repetitive cycles of 95 °C for 15 s and 60 °C for 1 min. Ribosomal 18S RNA was assayed in each sample to normalize RNA loading as previously described by Ross et al.(2003).
|
). Differences in mRNA expression of IGF-I and IGF-1R were determined by sub-tracting the target CT of each sample from its respective ribosomal 18S CT value, which provides the sample 
CT value. Calculation of the CT involves using the highest sample CT value as an arbitrary constant to subtract from all other CT sample values. Fold differences in gene expression of the target gene are equivalent to 2–CT.
|
Ligand blotting
Uterine flushings were prepared for ligand blotting by concentrating 4 ml of the flushing using a Centricon 10 concentrator (Amicon, Beverly, MA, USA) with a 10 000 molecular weight cut off. Protein content in the concentrated uterine flushing sample was determined by using the Bio-Rad Protein Assay Kit II (Bio-Rad, Hercules, CA). IGFBPs in the uterine flushings were analysed by one-dimensional SDS-PAGE as described by Echternkamp et al.(1994). Protein (50 µg) from the concentrated uterine flushing was mixed with 21 µl non-reducing denaturation buffer (BioRad, Hercules, CA, USA). Bovine follicular fluid, diluted 10-fold, was utilized as a positive control to identify band size and IGFBPs in the porcine uterine flushings. Samples were denatured by heating to 100 °C for 3 min, centrifuging at 4657 g for 3 min and were then separated using 12% (w/v) PAGE for 65 min at a constant current of 25 mA per gel. After separation, proteins in the gel were electrophoretically transferred to nitrocellulose paper (Midwest Scientific, St Louis, MO, USA) and subsequently ligand blotted (16 h at 4 °C) using recombinant human 125I-labelled IGF-I and IGF-II. The next day, the nitrocellulose blots were washed, dried, and exposed to X-ray film at –80 °C for 21 days.
Statistical analysis
Data were analysed by least square ANOVA using the Proc Mixed procedure of SAS (SAS 1985). The statistical method used to analyse uterine gene expression for IGF-I and IGF-IR, and IGF-I and IGF-II protein in the uterine flushings included effects of day, treatment, and day x treatment interaction.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
Quantitative RT-PCR
A day x treatment interaction (P < 0.003) was detected for quantitative RT-PCR analysis of endometrial IGF-I gene expression in E and Veh gilts (Table 2
). Oestrogen treatment on Days 9 and 10 of gestation decreased endometrial IGF-I gene expression approximately 3-fold compared with Veh gilts on Day 12 (Table 2). However, on Day 13 of gestation, endometrial IGF-I gene expression increased 2.5-fold in E compared with Veh gilts. Endometrial IGF-I expression was similar between treatments on Days 10, 15 and 17 of gestation.
A day x treatment interaction (P < 0.0004) was detected for endometrial IGF-IR gene expression (Table 2). IGF-IR mRNA expression was greater on Days 13 and 15 of gestation in E compared with Veh gilts (Table 2). Gene expression between Veh gilts on Days 13 and 15 of gestation was significantly different; however, in E gilts no change was observed between these two days.
Uterine lumenal content of IGF-I and IGF-II
Content of IGF-I in the uterine flushings of E and Veh gilts (Fig. 1) was affected by day (P < 0.01) and treatment (P < 0.03). Uterine lumenal IGF-I content in Veh gilts was greatest on Days 10, 12 and 13 (484, 611 and 690 ng respectively) of gestation, which was followed by a four-to sixfold decline on Days 15 (150 ng) and 17 (109 ng) of gestation. The content of IGF-I in uterine flushings from E gilts was similar to Veh gilts on Day 10, but uterine IGF-I content decreased 48–72 h earlier in E gilts (P < 0.03). The amount of IGF-I in uterine flushings of E-treated gilts sharply declined on Day 12 and was 10-fold less on Day 13 (60 ng) of gestation compared with Veh (690 ng) gilts. The content of IGF-I in uterine flushings was similar across treatments on Days 15 and 17 of gestation.
|
). Pregnant gilts treated with oestrogen on Days 9 and 10 of gestation had a sevenfold decrease in uterine lumenal content of IGF-II on Day 13 of gestation compared with Veh gilts (52 vs 370 ng). Uterine content of IGF-II was similar on all other days of gestation evaluated in the study.
|
). Ligand blot indicated that oestrogen treatment caused an earlier loss of IGFBPs as no bands were detected in uterine flushings from any of the days studied.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
The presence of IGF-IIR in the trophoblast (Corps et al. 1990) suggests that uterine and/or conceptus IGF secretion can regulate early conceptus development. In the present study, uterine lumenal content of IGF-I and IGF-II peaked on the day of conceptus elongation (Days 12 to 13) in Veh gilts. The content of IGF-I and IGF-II in uterine flushings decreased dramatically following conceptus elongation and the initiation of placental attachment to the uterine surface epithelium on Day 15 of gestation. Results from Veh gilts in the present study are consistent with previous publications on lumenal uterine IGF content in cyclic and pregnant pigs (Letcher et al. 1989, Geisert et al. 2001). Although there is a slight decline in endometrial IGF-I gene expression on Days 12 and 13 of pregnancy, gene expression on Days 15 and 17 returns to expression levels detected on Day 10. Thus, the decrease in IGF-I in uterine flushings following Day 13 is not related to a depression in endometrial IGF-I gene expression.
The high content of IGFs in the uterine lumen of the pig is associated with detection of IGFBPs in the uterine lumen. Insulin-like growth factor binding proteins regulate the biological activity of the IGF ligands in vivo (Firth & Baxter 2002). The IGFBPs share structural homology and have a high binding affinity for the IGF ligands. On Day 10 of the oestrous cycle and pregnancy, IGFBP-2 and IGFBP-3 are detected in the uterine lumenal fluids of cyclic and pregnant pigs when uterine lumenal content of IGF-I and IGF-II are high (Lee et al. 1998, Geisert et al. 2001). However, there is almost a complete loss of uterine lumenal IGFBPs on Day 12 of either the oestrous cycle or pregnancy (Geisert et al. 2001). The disappearance of IGFBPs observed in uterine lumenal flushings on Day 12 is due to an increase in IGFBP proteolysis rather than to down-regulation of IGFBP mRNA (Lee et al. 1998). The proteolysis of IGFBPs in the porcine uterine lumen may occur through activation of serine protease, tissue kallikrein and/or the metalloproteinases (Lee et al. 1998, Geisert et al. 2001). IGFs are regulated and stabilized through tertiary binding to IGFBPs. The degradation of IGFBPs within the uterine lumen may, in part, be responsible for the decreased content of IGF-I and IGF-II collected in uterine flushings after Day 13. Ballard et al.(1991) demonstrated that the normal 10 min half-life of 125I-IGF-I could be extended to greater than 15 h when bound to IGFBPs. Furthermore, IGFBP may play a role in prevention of premature binding and signalling of the ligands through the IGF-IR at the cellular level (Conover et al. 1990). It is possible that IGFBPs help sequester IGF-I and -II in the uterine lumen for release during the sensitive period of conceptus differentiation and trophoblast elongation. Thus the decline in lumenal IGF content following Day 12 does not reflect a lack of endometrial IGF-I gene expression, but rather the loss of IGFBPs to sequester IGFs in the uterine lumen. The spatiotemporal association of uterine IGFs and IGFBPs at the critical period in early porcine conceptus development and the alteration observed following oestrogen administration in the present study suggests that the uterine IGF system serves an important biological role in the establishment and maintenance of pregnancy.
The abundant presence of IGF-I receptors and ligand mRNA appear to parallel each other in the endometrium, indicating that IGFs may have an autocrine role in uterine function during the period of conceptus expansion (Simmen et al. 1992). In the current study, endometrial IGF-IR gene expression increased after the decrease in lumenal IGFs. Circulating concentrations of IGF-I and IGF-II are generally thought to depress expression of IGF-IR locally (Rosenfeld et al. 1982), which may explain the up-regulation of the IGF-IR mRNA on Days 15 and 17. Maintenance of endometrial IGF-I gene expression and loss of lumenal IGFBPs may allow IGFs to stimulate uterine tissue rather than sequestering the growth factors in the lumen during pregnancy.
Although oestrogen plays a major function in regulating the block to luteolysis and uterine changes in secretion and morphology for implantation in the pig, inappropriate exposure to oestrogen (i.e. delivered prior to the normal time of conceptus secretion on Days 11 to 12 of gestation) has a detrimental effect on conceptus survival. Consumption of feed containing the oestrogenic mycotoxin, zearalenone, causes total embryonic loss in swine (Long & Diekman 1984). Pope et al.(1986) first demonstrated that administration of oestrogen to gilts on Days 9 and 10 of gestation resulted in complete embryo mortality before Day 30 of gestation; however, no effect was observed when oestrogen was administered on Days 12 to 13 (time of endogenous conceptus oestrogen secretion). Work in our laboratory demonstrated that premature exposure of the pregnant uterus to oestrogen (on Days 9 and 10) does not affect conceptus elongation on Day 12, but results in conceptus degeneration on Day 15 of pregnancy (Morgan et al. 1987, Gries et al. 1989). The cause of the early conceptus degeneration following endocrine disruption with oestrogen is not known. Blair et al.(1991) indicated that early oestrogen administration causes a loss of the uterine epithelial surface glycocalyx that could interfere with conceptus attachment to the uterine surface. Loss of porcine conceptuses at the time of placental attachment following oestrogen treatment is similar to the implantation failure caused by oestrogen in the mouse. Recently, the concentration and timing of oestrogen stimulation was demonstrated to function within a very narrow range to open the window for uterine receptivity in the mouse (Ma et al. 2003). High concentrations of oestrogen shorten the window of receptivity and cause implantation failure as a result of aberrant uterine gene expression during blastocyst attachment. The Ma et al.(2003) study provided direct evidence that oestrogen not only opens the window of uterine receptivity in the mouse, but also points to the fact that its concentration and timing are critical for ensuring proper downstream events essential for blastocyst implantation and survival.
Our results indicate that administration of oestrogen to gilts on Days 9 and 10 of pregnancy causes premature proteolysis of uterine lumenal IGFBPs. The disappearance of IGFBPs may, in part, be responsible for the early decline of IGF-I and IGF-II ligand on Days 12 and 13 in oestrogen-treated gilts. Corthorn et al.(1997) demonstrated that oestrogen stimulated tissue kallikrein activation in the uterine epithelium of the rat. Oestrogen activation of the uterine proteolytic enzymes such as tissue kallikrein and the matrix metalloproteinases that degrade the IGFBPs (Geisert et al. 2001) could be the mechanism by which the early porcine conceptus releases IGFs for its development in utero. The advanced increase in endometrial IGF-IR gene expression in oestrogen-treated (Day 13) compared with vehicle-treated (Day 15) gilts is consistent with the early decline of the IGFs in the uterine lumen. The precise nature of the loss of uterine lumenal IGFs following conceptus elongation suggests that the release of IGFs during Days 12 and 13 of pregnancy is very critical for subsequent development and survival of pig embryos. Although we cannot demonstrate a causal effect of premature loss of IGFs with later embryonic death from our current study, early oestrogen administration clearly causes a dramatic decline in IGFs before the critical period of conceptus elongation and differentiation. Mice devoid of the IGF-IIR undergo in utero mortality during gestation (see review by Jones & Clemmons 1995). Studies have demonstrated that the IGF-IIR is fundamental in embryonic development in the mouse (Barlow et al. 1991), and plays a major role in tissue remodelling and translocation of newly synthesized cathepsins to the lysosomes (Dahms et al. 1989). Thus, alteration in the normal synchrony of IGF release in the uterine lumen during early pregnancy may cause aberrant endometrial and/or conceptus gene expression during implantation. Microarray analysis of the endometrium from oestrogen-treated gilts has indicated that a number of genes are up- and down-regulated on Day 13 compared with controls (JW Ross, MD Ashworth and RD Geisert, unpublished observations). Therefore, endocrine disruption is not solely limited to the IGF system although IGFs could play roles in the alteration of many other genes as well.
The present study suggests proteolysis of the IGFBPs is clearly an endocrine disrupted event caused by the administration of oestrogen during early pregnancy in the pig. Bioavailability of endometrial IGFs prior to and during conceptus elongation and differentiation may be a fundamental essential for continued development and survival in the pig.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
Ballard FJ, Knowles SE, Walton PE, Edson K, Owens PC, Mohler MA & Ferraiolo BL 1991 Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1–3)IGF-I in rats. Journal of Endocrinology 128 197–204.[Abstract]
Barlow DP, Stoger R, Herrmann BG, Saito K & Schweifer N 1991 The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349 84–87.[CrossRef][Medline]
Bazer FW & Thatcher WW 1977 Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2
by the uterine endometrium. Prostaglandins 14 397–401.[CrossRef][ISI][Medline]
Blair RM, Geisert RD, Zavy MT, Yellin T, Fulton RW & Short EC 1991 Endometrial surface and secretory alterations associated with embryonic mortality in gilts administered estradiol valerate on days 9 and 10 of gestation. Biology of Reproduction 44 1063–1079.[Abstract]
Burghardt RC, Bowen JA, Newton GR & Bazer FW 1997 Extracellular matrix and the implantation cascade in pigs. Journal of Reproduction and Fertility Supplement 52 151–164.
Butler AA & LeRoith D 2001 Minireview: tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology. Endocrinology 142 1685–1688.
Chastant S, Monget P & Terqui M 1994 Localization and quantification of insulin-like growth factor-I (IGF-I) and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in pig embryos during early pregnancy. Biology of Reproduction 51 588–596.[Abstract]
Conover CA, Ronk M, Lombana F & Powell DR 1990 Structural and biological characterization of bovine insulin-like growth factor binding protein-3. Endocrinology 127 2795–2803.[Abstract]
Corps AN, Brigstock DR, Littlewood CJ & Brown KD 1990 Receptors for epidermal growth factor and insulin-like growth factor-I on pre-implantation trophoderm of the pig. Development 110 221–227.[Abstract]
Corthorn J, Figueroa C & Valdes G 1997 Estrogen and luminal stimulation of rat uterine kallikrein. Biology of Reproduction 56 1432–1438.[Abstract]
Dahms NM, Lobel P & Kornfeld S 1989 Mannose 6-phosphate receptors and lysosomal enzyme targeting. Journal of Biological Chemistry 264 12115–12118.
Dantzer V 1985 Electron microscopy of the initial stages of placentation in the pig. Anatomy and Embryology 17 281–293.
Echternkamp SE, Spicer LJ, Gregory KE, Canning SF & Hammond JM 1990 Concentrations of insulin like growth factor-I in blood and ovarian follicular fluid of cattle selected for twins. Biology of Reproduction 43 8–14.[Abstract]
Echternkamp SE, Howard JH, Roberts AJ, Grizzle J & Wise T 1994 Relationship among concentrations of steroids, insulin like growth factor-I, and insulin like growth factor binding proteins in ovarian follicular fluid of beef cattle. Biology of Reproduction 51 971–981.[Abstract]
Firth SM & Baxter RC 2002 Cellular actions of the insulin-like growth factor binding proteins. Endocrine Reviews 23 824–854.
Geisert RD & Yelich JV 1997 Regulation of conceptus development and attachment in pigs. Journal of Reproduction and Fertility Supplement 52 133–149.
Geisert RD, Brookbank JW, Roberts RM & Bazer FW 1982 Establishment of pregnancy in the pig: II. Cellular remodeling of the porcine blastocyst during elongation on day 12 of pregnancy. Biology of Reproduction 27 941–955.[CrossRef][ISI][Medline]
Geisert RD, Chamberlain CS, Vonnahme KA, Malayer JR & Spicer LJ 2001 Possible role of kallikrein in proteolysis of insulin-like growth factor binding proteins during the oestrous cycle and early pregnancy in pigs. Reproduction 121 719–728.[Abstract]
Green ML, Simmen RC & Simmen FA 1995 Developmental regulation of steroidogenic enzyme gene expression in the peri-implantation porcine conceptus: a paracrine role for insulin-like growth factor-I. Endocrinology 136 3961–3970.[Abstract]
Gries LK, Geisert RD, Zavy MT, Garrett JE & Morgan GL 1989 Uterine secretory alterations coincident to embryonic mortality in the gilt after exogenous estrogen administration. Journal of Animal Science 6 276–284.
Hettinger AM, Allen MR, Zhang BR, Goad DW, Malayer JR & Geisert RD 2001 Presence of the acute phase protein, bikunin, in the endometrium of gilts during estrous cycle and early pregnancy. Biology of Reproduction 65 507–513.
Irwin JC, Suen LF, Faessen GH, Popovici RM & Giudice LC 2001 Insulin-like growth factor (IGF)-II inhibition of endometrial stromal cell tissue inhibitor of metalloproteinase-3 and IGF-binding protein-1 suggests paracrine interactions at the decidua:trophoblast interface during human implantation. Journal of Clinical Endocrinology and Metabolism 86 2060–2064.
Jones JI & Clemmons DR 1995 Insulin-like growth factors and their binding proteins: biological actions. Endocrine Reviews 16 3–34.[CrossRef][ISI][Medline]
Ko Y, Choi I, Green ML, Simmen FA & Simmen RC 1994 Transient expression of the cytochrome P450 aromatase gene in elongation porcine blastocysts is correlated with uterine insulin-like growth factor levels during peri-implantation development. Molecular Reproduction and Development 37 1–11.[CrossRef][ISI][Medline]
Lee CY, Green ML, Simmen RC & Simmen FA 1998 Proteolysis of insulin-like growth factor-binding proteins (IGFBPs) within the pig uterine lumen associated with peri-implantation conceptus development. Journal of Reproduction and Fertility 112 369–377.[Abstract]
Letcher R, Simmen RCM, Bazer FW & Simmen FA 1989 Insulin-like growth factor-I expression during early conceptus development in the pig. Biology of Reproduction 41 1143–1151.[Abstract]
Long GG & Diekman MA 1984 Effect of purified zearalenone on early gestation in gilts. Journal of Animal Science 59 1662–1670.
Ma WG, Song H, Das SK, Paria BC & Dey SK 2003 Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. PNAS 100 2963–2968.
Morgan GL, Geisert RD, Zavy MT & Fazleabas AT 1987 Development and survival of pig blastocysts after oestrogen administration on day 9 or days 9 and 10 of pregnancy. Journal of Reproduction and Fertility 80 133–141.[Abstract]
Pope WF, Lawyer MS, Butler WR, Foote RH & First NL 1986 Response shift in the ability of gilts to remain pregnant following exogenous estradiol-17 beta exposure. Journal of Animal Science 63 1208–1210.
Rosenfeld RG, Hintz RL & Dollar LA 1982 Insulin-induced loss of insulin-like growth factor-I receptors on IM-9 lymphocytes. Diabetes 31 375–381.[Abstract]
Ross JW, Malayer JR, Ritchey JW & Geisert RD 2003 Characterization of the interleukin-1beta system during porcine trophoblastic elongation and early placental attachment. Biology of Reproduction 69 1251–1259.
SAS 1985 SAS User’s Guide: statistics (version 5.0). Cary, NC: Statistical Analysis System Institute Inc.
Sato T, Wang G, Hardy MP, Kurita T, Cunha GR & Cooke PS 2002 Role of systemic and local IGF-I in the effects of estrogen on growth and epithelial proliferation of mouse uterus. Endocrinology 143 2673–2679.
Simmen FA, Simmen RC, Geisert RD, Martinat-Botte F, Bazer FW & Terqui M 1992 Differential expression, during the estrous cycle and pre- and postimplantation conceptus development, of messenger ribonucleic acids encoding components of the pig uterine insulin-like growth factor system. Endocrinology 130 1547–1556.[Abstract]
Spicer LJ & Ecternkamp SE 1995 The ovarian insulin and insulin like growth factor system with an emphasis on domestic animals. Domestic Animal Endocrinology 21 1–15.
This article has been cited by other articles:
 |
|
 |
|
  M. D. Ashworth, J. W. Ross, J. Hu, F. J. White, D. R. Stein, U. DeSilva, G. A. Johnson, T. E. Spencer, and R. D. Geisert Expression of Porcine Endometrial Prostaglandin Synthase During the Estrous Cycle and Early Pregnancy, and Following Endocrine Disruption of Pregnancy Biol Reprod, June 1, 2006; 74(6): 1007 - 1015. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
