Biomedical subjects

Asgerally T Fazleabas

Publications and source records attributed to Asgerally T Fazleabas.

At least 19 recordsLinked to original sources

PubMed2006

Decidualization regulates the expression of the endometrial chorionic gonadotropin receptor in the primate.

Chorionic gonadotropin (CG) plays an important role in establishing a receptive endometrium by directly modulating the function of both endometrial stromal and epithelial cells in the baboon. The focus of this study was to characterize changes in CG receptor (LHCGR, also known as CG-R) expression during the menstrual cycle and early pregnancy, particularly during decidualization. LHCGR was localized by using a peptide-specific antibody generated against the extracellular domain. Immunostaining was absent in any of the cell types during the proliferative phase of the cycle. In contrast, during the secretory phase, both luminal and glandular epithelial cells stained positively. Stromal staining was confined to the cells around spiral arteries (SAs) and in the basalis layer. This stromal staining pattern persisted at the implantation site between Days 18 and 25 of pregnancy and after CG infusion. However, as pregnancy progressed (Days 40 to 60), staining for LHCGR was dramatically decreased in the stromal cells. These data were confirmed by nonisotopic in situ hybridization. To confirm whether the loss of LHCGR was associated with a decidual response, stromal fibroblasts were decidualized in vitro, and cell lysates obtained after 3, 6, and 12 days of culture were analyzed by Western blotting. LHCGR protein decreased with the onset of decidualization in vitro, confirming the in vivo results. Addition of CG to decidualized cells resulted in the reinduction of LHCGR in the absence of dbcAMP. We propose that CG acting via its R on stromal cells modulates SA in preparation for pregnancy and trophoblast invasion. As pregnancy progresses, further modification of SA by migrating endovascular trophoblasts and subsequent decidualization results in the downregulation of LHCGR. This inhibition of LHCGR expression also coincides with the decrease of measurable CG in peripheral circulation.

Animals↗

PubMed2006

Human chorionic gonadotropin and decidualization in vitro inhibits cytochalasin-D-induced apoptosis in cultured endometrial stromal fibroblasts.

Endometrial apoptosis increases from the proliferative phase through the secretory phase and peaks at menses. However, with the onset of pregnancy, the corpus luteum is rescued and stromal cells, instead of undergoing apoptosis, reorganize the cytoskeleton and then begin to differentiate. We hypothesized that in the presence of hormones (estradiol-17beta and medroxyprogesterone acetate), chorionic gonadotropin (hCG) as an early embryonic signal, and induction of decidualization by dibutyryl-cAMP (dbcAMP), endometrial stromal cells are rescued by the regulation of proteins that inhibit apoptosis. The percentage of cells stained with annexin V, an early apoptotic marker, increased dramatically after cytoskeletal disruption with cytochalasin D compared with non-cytochalasin-D-treated controls (P < 0.05). However, treatment of cells with hCG or dbcAMP in the presence of hormones significantly (P < 0.05) decreased the percentage of annexin-V-stained cells compared with cells treated with cytochalasin D alone. This inhibition was further confirmed by immunodetection of cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The inhibition of apoptosis by hCG and dbcAMP was via the intrinsic pathway because the cytochalasin-D-treated cells stained intensely for Bax, whereas the cells treated with hormones, hCG, or dbcAMP stained predominantly for Bcl-2. Treatment of cytochalasin-D-treated cells with hormones and dbcAMP resulted in an increase in the secretion of IGF-binding protein-1 (IGFBP-1) and prolactin. Treatment of cytochalasin-D-treated cells with recombinant IGFBP-1 and prolactin also inhibited apoptosis. These data suggest that under in vitro conditions, both hCG and the induction of decidualization play a direct role in preventing uterine stromal cells from undergoing apoptosis. Furthermore, this inhibition of apoptosis may be mediated in part by IGFBP-1 and prolactin and the alteration in the expression of Bcl-2 and Bax.

Annexin A5↗

PubMed2006

The estrogen early response gene FOS is altered in a baboon model of endometriosis.

Endometriosis, the presence of a functional endometrium outside of the uterine cavity, is associated with infertility. In our simulated model of pregnancy in baboons with experimental endometriosis, hCG infusion fails to induce expression of the immunoregulatory protein glycodelin. To test the hypothesis that the development of endometriosis is associated with an aberrant endometrial immunological environment, we examined the expression of a series of immunoregulatory genes in endometrium from baboons with and without endometriosis. Six months following intraperitoneal inoculation with menstrual endometrium, eutopic endometrium was surgically collected between Days 9 and 11 postovulation. Control endometrium was similarly collected from disease-free animals. Total RNA was extracted, and biotinylated cDNA probes were hybridized to the SuperArray GEArray Q series Th1/Th2/Th3 cDNA array, representing 96 genes. Gene expression levels were determined using ScanAlyze and GEArray Analyzer software. Seven genes were upregulated, including JUND, FOS, CCL11, NFKB1 and others, in the endometrium from baboons with endometriosis compared with the endometrium from disease-free animals; one gene, IL1R1, was downregulated. Quantitative RT-PCR confirmed upregulation of FOS and CCL11 in endometriotic eutopic endometrium. Immunohistochemical analysis revealed altered levels and distribution of FOS protein in the eutopic endometrium of baboons with induced endometriosis. These data suggest that in an induced model of endometriosis an aberrant eutopic immunological environment results in a decreased apoptotic potential and in rapid alterations in endometrial gene expression. We propose that the reduced fecundity associated with endometriosis has a multifold etiology in spontaneous and induced disease.

Animals↗

PubMed2006

Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and proteins in normal human prostate and prostatic adenocarcinoma.

Human leukocyte antigen-G (HLA-G) is a major histocompatibility complex class Ib gene expressed in normal organs and in some tumors. The glycoproteins encoded by this gene are best known for their immunosuppressive properties. Because isoform-specific expression of HLA-G in male reproductive organs has not been reported, we investigated HLA-G1, -G2, -G5, -G6 mRNAs and proteins in four-to-five samples of normal prostate glands, prostates with benign prostatic hyperplasia and prostate adenocarcinomas using RT-PCR and immunohistochemistry. All tissues contained HLA-G1, -G2, -G5 and -G6 specific mRNAs, but only HLA-G5 protein was detectable. In normal prostate glands, HLA-G5 protein was prominent in the cytoplasm of tubuloglandular epithelia and in glandular secretions. Staining was reduced in samples of benign prostatic hyperplasia but remained localized to the cytoplasm of glandular epithelia and secretions. In prostatic adenocarcinomas, HLA-G5 protein was detectable mainly in the secretions. Thus, HLA-G5 but not HLA-G1, -G2 or -G6 is produced in the normal prostate and is present in prostatic secretions. In addition, normal cellular localization is disturbed in benign and malignant prostatic adenocarcinomas. The results are consistent with this molecule may influencing female immune receptivity to sperm and suggest that such immunosuppression could be disturbed in men with prostatic adenocarcinomas.

Adenocarcinoma↗

PubMed2006

Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria.

The expression of human CYR61 (cysteine-rich, angiogenic inducer, 61; CCN1) mRNA has been previously shown to be deregulated in the endometrium of women with endometriosis. We have chosen the baboon model (Papio anubis) of induced endometriosis to clarify whether CYR61 mRNA upregulation is predisposed to an inappropriately differentiated endometrium or is deregulated as a response to the presence of ectopic lesions. In the baboon, endometrial CYR61 mRNA expression underwent moderate cyclical variation, with a significant 7.3-fold increase detected at Day 2 postmenses when compared to endometrium from the proliferative and secretory phases. The CYR61 transcript was extensively upregulated in the eutopic endometrium from all baboons with induced endometriosis, as early as 1 mo postinoculation of menstrual tissue into the peritoneal cavity. CYR61 mRNA expression then decreased throughout progression of the disease, but remained higher compared to control tissues. Ectopic endometriotic lesions showed a further increase in CYR61 mRNA, with highest expression found in red lesions. Moreover, the expression levels of CYR61 transcripts correlated significantly with those of VEGF. Immunohistochemistry revealed the presence of CYR61 protein in glandular and luminal epithelial cells as well as in blood vessels of eutopic and ectopic endometrium. As in humans, increased levels of CYR61 mRNA correlated with the development of endometriosis in baboons. The increase of CYR61 mRNA in eutopic endometrium of baboons following peritoneal inoculation with menstrual endometrium provides evidence for a feedback mechanism from resulting lesions to induce a shift in gene expression patterns in the eutopic endometrium.

Animals↗

PubMed2006

A baboon model for endometriosis: implications for fertility.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility in women in the reproductive age group. Although the existence of this disease has been known for over 100 years our current knowledge of its pathogenesis and the pathophysiology of its related infertility remains unclear. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed a model of this disease in the non-human primate, the baboon (Papio anubis). Intraperitoneal inoculation of autologous menstrual endometrium results in the development of endometriotic lesions with gross morphological characteristics similar to those seen in the human. Multiple factors have been implicated in endometriosis-associated infertility. We have described aberrant levels of factors involved in multiple pathways important in the establishment of pregnancy, in the endometrium of baboons induced with endometriosis. Specifically, we have observed dysregulation of proteins involved in invasion, angiogenesis, methylation, cell growth, immunomodulation, and steroid hormone action. These data suggest that, in an induced model of endometriosis in the baboon, an increased angiogenic capacity, decreased apoptotic potential, progesterone resistance, estrogen hyper-responsiveness, and an inability to respond appropriately to embryonic signals contribute to the reduced fecundity associated with this disease.

Animals↗

PubMed2006

A baboon model for inducing endometriosis.

Endometriosis is a disease that is associated with severe pelvic pain and is a major cause of infertility in women. It is an enigmatic disease whose etiology and pathophysiology has been studied to a limited extent. The events associated with the establishment of the disease and mechanisms associated with infertility are difficult to assess in a systemic manner in women. In order to understand the early and progressive events associated with the establishment of the disease, we have developed a baboon model in which the disease can be induced. This induction manifests itself in a manner that recapitulates the spontaneous disease. The advantage of the induced model is that the progressive changes in both the ectopic and eutopic endometrium can be studied in a nonhuman primate model at specific times during the menstrual cycle and as the disease process continues.

Animals↗

PubMed2006

A baboon model for simulating pregnancy.

Estrogen and progesterone secreted by the corpus luteum regulate the function of the uterine endometrium in preparation for pregnancy. Embryonic signals superimposed on this steroid hormone-primed uterus further modulate the uterine environment to make it conducive to pregnancy. Understanding the signaling mechanisms that initiate the embryonic-maternal dialog in humans is not feasible. In an effort to elucidate the role of chorionic gonadotropin as a mediator of endometrial function in addition to its luteotrophic role, we have developed a simulated pregnant model in the baboon. Infusion of chorionic gonadotropin in a manner that mimics blastocyst transit induces major changes in the morphology and secretory activity of the endometrium. This model provides a method by which the function of various embryonic factors on endometrial can be tested in an in vivo model.

Animals↗

PubMed2006

Methods for evaluating histocompatibility antigen gene expression in the baboon.

A wide variety of techniques has been developed for qualitative and quantitative analysis of gene expression in human cells and tissues. Two commonly used methods are reverse-transcription (RT)-polymerase chain reaction (PCR) to analyze the transcribed messenger RNAs (mRNA) and immunohistochemistry to detect the translated proteins. These techniques can be modified and adapted for use in analyzing gene expression in animal models. In particular, as a result of the close phylogenetic relationship between humans and nonhuman primates, human reagents, especially antibodies, cross-react with nonhuman primate tissues. However, the results are not always satisfactory as some antibodies may cross-react with irrelevant antigens in these tissues. In this chapter, we describe the use of RT-PCR and immunohistochemical techniques to analyze expression of Paan-AG, a novel class lb major histocompatibility complex antigen in the olive baboon (Papio anubis) placenta. We used Paan-AG-specific primers to amplify Paan-AG transcripts from baboon placenta, and generated Paan-AG isoform-specific polyclonal antibodies for use in immunohistochemistry.

Animals↗

PubMed2006

Mitogen-activated protein kinase is involved in the progesterone-mediated induction of baboon glycodelin.

In the human and non-human primate the major secretory product of the uterine glandular epithelial cells is glycodelin. The expression of glycodelin is associated with elevated progesterone levels as its production peaks during the late luteal phase of the menstrual cycle and in early pregnancy. Consistent with our previous studies, we found that the majority of the progestin responsiveness of the baboon glycodelin promoter was retained in the -20+48 region, a region devoid of progestin- and Sp1-response elements. Using serial 5' and 3' deletions of 10 basepairs of the promoter within the pGL3Basic vector, we identified the 5' and 3' limits required for progestin responsiveness as -22 and +18, respectively. When the same regions were cloned into the pGL3Promoter vector, a construct that contains the heterologous SV40 promoter, progestin did not enhance expression. Mutation of the DNA binding domain of the progesterone receptor, which disrupts its ability to activate the progesterone response element, does not obliterate its ability to induce expression via the baboon glycodelin promoter. Inhibitors of protein tyrosine kinases, genistein and AG18, blocked the progestin-mediated induction as did an inhibitor of MEK, PD98059, but not an inhibitor of p38 MAP kinase, SB202190. These findings imply that glycodelin induction in response to progestins involves a nongenomic mechanism through the ERK1/2 branch of the MAP kinase pathway. The ultimate target may be a factor involved in the initiation of glycodelin gene transcription.

Animals↗

PubMed2005

Outcomes of an intensive summer course in reproductive biology.

The Frontiers in Reproduction (FIR) course has been held annually, starting in 1998, at the Marine Biological Laboratories in Woods Hole, MA. To evaluate the impact of the FIR course in training reproductive biologists, a group of participants who completed the course between 1998 and 2002 were surveyed. The major findings of the survey were that: (1) FIR had a positive impact on the overall career development of the participants; (2) a significant majority (97%) continue to conduct research in the reproductive sciences; (3) 58% had successfully competed for grant funding; and (4) manuscripts by participants were published in higher-impact journals. In summary, FIR has had an overall positive influence worldwide on the training of future scientists whose research interests and studies are focused on the reproductive sciences.

Biology↗

PubMed2005

In vivo infusion of interleukin-1beta and chorionic gonadotropin induces endometrial changes that mimic early pregnancy events in the baboon.

Both human chorionic gonadotropin (hCG) and IL-1beta induce changes in the endometrium that are associated with the establishment of pregnancy. We investigated the synergistic effect of these two embryonic signals on endometrial function using a baboon model of simulated pregnancy. Recombinant hCG (30 IU/d) was infused between d 6 and 10 post ovulation (PO) to mimic blastocyst transit. On the expected day of implantation (d 10 PO), IL-1beta (12 ng/d) or IL-1 receptor antagonist (IL-1Ra; 12 ng/d) was infused for an additional 5 d. Endometria were harvested on d 15 PO. Both hCG and hCG plus IL-1beta induced marked differences in the distribution of alpha-smooth muscle actin, proliferation marker Ki67, decidualization marker IGF-binding protein-1, and cyclooxygenase-1. The most marked effect of IL-1beta was the induction of IGF-binding protein-1 protein in stromal cells close to the apical surface, whereas cyclooxygenase-1 was down-regulated in the glandular epithelium. Protein arrays of uterine flushings showed significant suppression of death receptors, Fas and TNF receptor 1, in the hCG- with or without IL-1beta-treated groups, suggesting an inhibition of apoptosis. Additionally, cytotoxic T lymphocyte antigen-4, matrix metalloproteinase-3, and IL-4 were suppressed in treated animals compared with controls. However, no differences were observed in cytokine profile between hCG-treated and hCG- plus IL-1beta-treated baboons. This study confirms that in preparation for pregnancy, the primate endometrium undergoes both morphological and functional changes, which are modulated by hCG and IL-1beta, that lead to the inhibition of apoptosis and the development of an immunotolerant environment. These changes suggest that infusion of IL-1beta at the time of implantation into the nonpregnant baboon treated with hCG synergizes with hCG and mimics the early endometrial events associated with the presence of an embryo.

Actins↗

PubMed2005

Compartmental distinctions in uterine Muc-1 expression during early pregnancy in cynomolgous macaque (Macaca fascicularis) and baboon (Papio anubis).

BACKGROUND: Loss of the transmembrane mucin, Muc-1, is a molecular correlate of the acquisition of uterine receptivity to embryo adhesion in most species examined. In macaques, two distinct adhesion events occur at opposite sides of the uterus. Attachment to the secondary site is delayed relative to the primary site. The aim was to determine if Muc-1 is removed at secondary sites prior to trophoblast attachment. METHODS: We examined Muc-1 expression in the uteri of cynomolgus macaque and baboon during early implantation by immunocytochemistry. RESULTS: Luminal epithelia were devoid of Muc-1 at all stages examined at both primary and secondary adhesion sites. Loss of Muc-1 in luminal epithelia was found to be maternally determined, accompanied membrane transformation in both macaque and baboon, and at secondary implantation sites, preceded trophoblast attachment. In contrast, glandular epithelia in pregnant macaques exhibited a temporal and compartmentalized gradient of Muc-1 loss confined to the implantation sites. Glandular epithelia in the pregnant baboon uterus were uniformly negative for Muc-1. CONCLUSIONS: Restriction of the Muc-1 loss in glandular epithelia to conceptual cycles may reflect the fundamental distinctions among epithelia of the various uterine compartments and the differential modulation of Muc-1 that occurs within these compartments in conceptual and non-conceptual cycles.

Animals↗

PubMed2005

Prevention of endometrial apoptosis: randomized prospective comparison of human chorionic gonadotropin versus progesterone treatment in the luteal phase.

To study control of apoptosis in human endometrium, we examined late luteal-phase endometrial biopsies obtained in the late luteal phase for evidence of apoptosis and compared the effects of exogenous human chorionic gonadotropin (hCG) and progesterone on this process. Using a controlled, prospective, and randomized study design, 12 healthy, fertile, reproductive-age women (ages 20-34 yr) with regular menstrual cycles (range, 26-32 d) were recruited. Each underwent an endometrial biopsy 12 d after a urinary LH surge in a control and treatment cycle. After biopsy in a natural cycle, subjects were randomized to receive luteal doses of either 200 mg intravaginal progesterone (d 18-27) or a single im injection of 10,000 IU of hCG (d 19) followed by repeat endometrial biopsy and collection of serum on d 26. Apoptosis was assessed by DNA laddering, localizing apoptotic bodies using immunofluorescent labeling of DNA fragments (the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method), and immunohistochemical assessment of apoptosis markers bcl-2, bcl-x, and bax. Serum progesterone levels were compared between treatment groups. Evidence of apoptosis in control cycles was significantly reduced in endometrium after both luteal-phase treatments. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling results demonstrated significantly less apoptosis in the hCG treatment group compared with controls. Immunostaining for bcl-2 was higher in hCG- and progesterone-treated cycles, whereas bax expression was decreased and bcl-x immunostaining was not different between treatments. Serum progesterone levels were highest in the hCG-treated group, although statistical significance was not reached (P = 0.08). These results demonstrate that signs of apoptosis, already apparent by d 26 of the menstrual cycle can be reduced with either hCG or progesterone treatment. The clinical utility of these findings includes a rational use of luteal-phase support for treatment of women with infertility and/or recurrent pregnancy loss.

Adult↗

PubMed2005

Novel concepts of human chorionic gonadotropin: reproductive system interactions and potential in the management of infertility.

OBJECTIVE: To extensively review the scientific literature on the potential sites of hCG action and the role of this hormone on reproductive processes not necessarily related to the classic hCG functions of supporting early pregnancy. DESIGN: Review of the international scientific literature and the authors' personal research experience in this area. RESULT(S): The LH/hCG receptor has an almost ubiquitous distribution in reproductive organs, thus suggesting that the actions of hCG might be more extensive than previously thought. Independently of FSH, low-dose hCG can support development and maturation of larger ovarian follicles that have acquired granulosa cells LH/hCG receptors, potentially providing effective and safer ovulation induction regimens. Human chorionic gonadotropin seems to be capable of improving uterine receptivity by enhancing endometrial quality and stromal fibroblast function. Furthermore, through its actions on insulin-like growth factor binding protein-1 and vascular endothelial growth factor, hCG might stimulate endometrial angiogenesis and growth and extend the implantation window, thus making pregnancy more likely. CONCLUSION(S): Mounting evidence indicates that hCG could be mediating relevant actions enhancing fertility and the efficacy of therapeutic procedures used in the management of infertility. Greater understanding of the physiologic roles that hCG plays in human reproduction might suggest novel clinical applications for this traditional hormone of pregnancy.

Animals↗

PubMed2004

Potential regulatory sequences in the untranslated regions of the baboon MHC class Ib gene, Paan-AG, more closely resemble those in the human MHC class Ia genes than those in the class Ib gene, HLA-G.

The baboon major histocompatibility complex (MHC) class Ib gene, Paan-AG, is structurally similar to the human MHC class Ia gene, HLA-A, but exhibits characteristics similar to those of the class Ib gene HLA-G. These include limited polymorphism, alternative splicing of a single message, and restricted tissue distribution, with high expression in the placenta. In order to determine whether regulatory elements controlling expression of Paan-AG resemble those of HLA-A or HLA-G, we cloned the 5' and 3' untranslated regions of Paan-AG. Unexpectedly, sequence comparisons showed that potential regulatory elements in Paan-AG strikingly resembled those in HLA-A and differed in major respects from those in HLA-G. Unlike HLA-G, Paan-AG contained an intact interferon-gamma stimulated response element (ISRE) in the promoter. Studies using luciferase reporter assays showed that the Paan-AG ISRE was functional. The basal activity of the Paan-AG ISRE and its response to interferon-gamma was similar to that of class Ia MHC genes. Further, we identified an ISRE in the 3' untranslated region of Paan-AG that is known to be functional in HLA-A2 but is deleted in HLA-G. These experiments predict that functional studies may demonstrate differences in regulation of expression of Paan-AG and HLA-G genes, which could restrict the use of the baboon as a primate model for studying HLA-G expression and function.

Animals↗

PubMed2004

Chorionic gonadotropin and uterine dialogue in the primate.

Implantation is a complex spatio-temporal interaction between the growing embryo and the mother, where both players need to be highly synchronized to be able to establish an effective communication to ensure a successful pregnancy. Using our in vivo baboon model we have shown that Chorionic Gonadotropin (CG), as the major trophoblast derived signal, not only rescues the corpus luteum but also modulates the uterine environment in preparation for implantation. This response is characterized by an alteration in both the morphological and biochemical activity in the three major cell types: luminal and glandular epithelium and stromal fibroblasts. Furthermore, CG and factors from the ovary have a synergistic effect on the receptive endometrium. Novel local effects of CG which influence the immune system to permit the survival of the fetal allograft and prevent endometrial cell death are also discussed in this review. An alternate extracellular signal-regulated kinase (ERK) activation pathway observed in epithelial endometrial cells and the possibility of differential expression of the CG/LH-R isoforms during gestation, open many questions regarding the mechanism of action of CG and its signal transduction pathway within the primate endometrium.

Animals↗

PubMed2004

Uterine receptivity and implantation: the regulation and action of insulin-like growth factor binding protein-1 (IGFBP-1), HOXA10 and forkhead transcription factor-1 (FOXO-1) in the baboon endometrium.

In primates, the phase of the menstrual cycle when the uterus becomes receptive is initially dependent on estrogen and progesterone. Further morphological and biochemical changes are induced as a result of biochemical signals between the embryo and the maternal endometrium. Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation and is similar to that described for the rhesus macaque. In the baboon, when chorionic gonadotropin is infused in a manner that mimics blastocyst transit, this has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial plaques are evident. The glandular epithelium responds by inducing transcriptional and post-translational modifications in the major secretory product, glycodelin. The stromal fibroblasts initiate their differentiation process into a decidual phenotype and are characterized by the expression of actin filaments. Decidualization, is the major change that occurs in the primate endometrium after conception. During this process the fibroblast-like stromal cells change morphologically into polygonal cells and express specific decidual proteins. Studies in the baboon demonstrated that insulin-like growth factor binding protein-1 (IGFBP-1) gene expression is a conceptus-mediated response. Subsequent studies in vitro established that IGFBP-1 is transcriptionally regulated by FOXO1 and HOXA10 which together upregulate the IGFBP-1 promoter activity. A baboon endometriosis model was utilized to determine if the changes observed during uterine receptivity in normally cycling animals were compromised. The data suggests that in animals with disease, markers of uterine receptivity are not appropriately expressed in the eutopic endometrium. It is possible that these differences influence the fertility of the animals with disease and the baboon could be used as a primate model to study the causes of infertility as a result of endometriosis.

Animals↗