Mol. Hum. Reprod. Advance Access originally published online on October 4, 2006
Molecular Human Reproduction 2006 12(12):749-754; doi:10.1093/molehr/gal082
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Deficient expression of monoamine oxidase A in the endometrium is associated with implantation failure in women participating as recipients in oocyte donation
1Laboratorio de Inmunología de la Reproducción, Universidad de Santiago de Chile, 2Instituto Chileno de Medicina Reproductiva, 3Millenium Institute for Fundamental and Applied Biology, 4Clínica Las Condes, Santiago, Chile and 5Laboratory of Molecular Technology, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD, USA
6 To whom correspondence should be addressed at: Alameda 3363, Casilla 40, Correo 33, Santiago, Chile. E-mail: lvelasqu{at}lauca.usach.cl
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Abstract |
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Successful implantation depends both on the quality of the embryo and on the endometrial receptivity. The latter depends on progesterone-induced changes in gene expression, a process that has been characterized by microarray analysis. One of the genes whose transcription appears to be enhanced during the receptive period is monoamine oxidase A (MAO-A). Our first objective was to confirm the increased expression of MAO-A in the endometrium during the receptive phase of spontaneous normal cycles using real time PCR and immunofluorescence. The second objective was to examine the endometrial expression of MAO-A during the receptive phase induced by exogenous estradiol (E2) and progesterone in patients whose endometrium was shown to have been either receptive or non-receptive to embryo implantation in repeated cycles of oocyte donation. Results showed that MAO-A transcript levels increased between the pre-receptive (LH+3) and receptive phase (LH+7) in all spontaneous cycles examined, with a median increase of 25-fold. Immunofluorescent labelling demonstrated MAO-A localization to the glandular and luminal epithelium with an increasing positive score between LH+3 and LH+7. Conversely, prior failure of embryo implantation was associated with a 29-fold decrease in MAO-A mRNA levels and a substantial reduction in MAO-A protein immunofluorescent label score. These results show a strong association between endometrial receptivity and MAO-A expression in the endometrial epithelium, suggesting an important role for this enzyme in normal implantation.
Key words: monoamine oxidase A/endometrium/implantation failure/implantation window/oocyte donation
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Introduction |
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Implantation failure may result from a variety of abnormalities affecting the gametes, the embryo, the genital tract or the hormonal milieu and is one of the leading causes of ‘unexplained infertility’ estimated to occur in 10–15% of couples seeking fertility treatment (Crosignani et al., 1993
). Implantation depends both on the blastocyst and on the endometrium. Although defects in uterine receptivity are viewed with scepticism by some, growing evidence suggests that for successful implantation the quality of the endometrium is no less important than the quality of the blastocyst (Valbuena et al., 1999).
Current data indicate that the expression of some genes at the onset of receptivity is temporarily turned on or increased whereas others are temporarily turned off or decreased (Lessey, 2000; Sunder and Lenton, 2000; Carson et al., 2002; Kao et al., 2002; Martin et al., 2002; Borthwick et al., 2003; Riesewijk et al., 2003; Mirkin et al., 2005). Many of these changes are likely to be essential for implantation and maintenance of pregnancy; however, distinguishing a mere association from a cause–effect relationship has proven difficult in the human female.
A gene whose expression increases during the receptive phase is the one coding for monoamine oxidase A (MAO-A), which is in keeping with previous findings of a marked increase in MAO-A activity in the human endometrium during the mid-luteal phase (Cohen et al., 1965; Southgate et al., 1968; Ryder et al., 1980). These data suggest that this enzyme may play an important role in receptivity to embryo implantation.
MAO is localized in the outer membrane of mitochondria in neuronal and glial cells among others (Cohen et al., 1965; Southgate et al., 1968; Mazumder et al., 1980; Ryder et al., 1980) and catalyses the oxidative deamination of a variety of monoamines using flavin adenine dinucleotide as cofactor. Two forms of MAO, designated MAO-A and MAO-B, have been identified on the basis of biochemical properties (Johnston, 1968) and nucleic acid sequence (Bach et al., 1988). MAO-A oxidizes preferentially biogenic amines such as serotonin, norepinephrine (NE) and epinephrine although dopamine is a substrate for both (Johnston, 1968). Both isoenzymes are co-expressed in the majority of human tissues except placenta, which predominantly expresses MAO-A, whereas platelets and lymphocytes predominantly express MAO-B (Shih and Thompson, 1999).
Infertile women who have been submitted repeatedly and unsuccessfully to embryo transfer, using good quality embryos, represent a convenient model for examining possible defects in gene expression that render the endometrium non-receptive. The model is more robust when these women have been the recipients of embryos originated from oocyte pools that generated embryos that implanted successfully in the oocyte donors. The probability that implantation failure in these cases is due to an intrinsic endometrial defect is further enhanced by absence of discernible male factors. Additional strength of this model is attained when embryo transfer is performed in endometrial cycles induced with exogenous estradiol (E2) and progesterone as adequate hormonal stimulation is insured.
On the basis of this reasoning, we hypothesized that implantation failure in infertile women with the features outlined above, may be due to an intrinsic defect in the expression of genes whose transcript level normally increases during the receptive period.
The experimental strategy chosen to test this hypothesis was to compare endometrial gene expression profiles during an artificially induced implantation window in two groups of women, one having a past history of successful implantation and the other the antecedent of failed implantation in repeated cycles in an oocyte donation program. Here, we describe our findings in relation to MAO-A expression, whereas general results of the microarray profiling in the two groups will be reported elsewhere.
We first confirmed the increased expression of MAO-A in the endometrium during the receptive phase of spontaneous menstrual cycles of fertile women, using real time PCR and immunofluorescence. Subsequently, we compared the endometrial expression of MAO-A during the implantation window of artificially induced endometrial cycles in the two group of patients. Herein, we show for the first time that the deficient expression of a gene in the endometrium during the receptive phase is consistently associated with refractoriness to implantation in infertile women.
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Materials and methods |
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Approval and informed consent
This study was approved independently by the Ethics committee of the Chilean Institute for Reproductive Medicine, University of Santiago de Chile and that of Clinica Las Condes. All women participating in this study were informed of the procedures and purpose of the study and signed a consent form.
Endometrial biopsies
Spontaneous cycles of normal fertile women
Sixteen endometrial biopsies were obtained from eight healthy fertile women aged between 28 and 39 years, who had regular menstrual cycles (26–35 days), had been surgically sterilized, had no history of endometriosis or pelvic inflammatory disease and were not using drugs or taking hormones. Two samples were obtained within the same cycle from each volunteer, one on day 3 (LH+3, pre-receptive phase) and the other on day 7 (LH+7, receptive phase) after the LH peak (LH peak=day 0). Endometrial biopsies were taken from the uterine fundus using Pipelle catheters (CCD Laboratories, Paris) under sterile conditions. These biopsies were used to confirm the differential gene expression of MAO-A in the endometrium during the pre-receptive and receptive phase of the luteal phase.
Occurrence of ovulation was confirmed by monitoring follicular growth and rupture with daily transvaginal ultrasound (TVU). A blood sample of 10ml was obtained daily from the antecubital vein, when the leading follicle reached 12mm until ovulation and every other day thereafter until the first biopsy was taken. E2, progesterone, LH and FSH were measured in these samples to pinpoint the LH peak and confirm retrospectively that the biopsies had been preceded by a normal mid-cycle endocrine profile.
Induced cycles in infertile and fertile women
Seventeen endometrial biopsies were obtained during the receptive period from three groups of volunteer women: Group A, women who had previously participated as recipients in oocyte donation cycles and who repeatedly failed to have implantation of the transferred embryos (n=5, one of these women had no ovarian function); group B, women who had succeeded in having implantation as recipients in the same oocyte donation program (n=6, three of these women had no ovarian function) and group C, fertile women who conceived spontaneously in natural cycles and had given birth to three or more children (n=6). In groups A and B, the same oocyte pool that provided their embryos also provided embryos that implanted successfully in the uteri of the donors. Women having spontaneous menstrual cycles received first appropriate treatment to suppress spontaneous cyclicity as illustrated in Figure 1. This treatment started on the first day of menstrual bleeding or at any convenient time in amenorrhoic women. Women with ovarian function received contraceptive pills containing levonorgestrel 0.25mg and ethinyl estradiol 0.05mg for 10–21 days, according to the convenience of the biopsy schedule. Down-regulation with the GnRH agonist leuprolide acetate (Lupron; TAP pharmaceuticals, Deerfield, IL, USA) was initiated on the last day of contraceptive administration at a dose of 0.5mg s.c. daily for 7 days. Women with no ovarian function did not receive GnRH agonist therapy. In the case of cycling women, treatment with leuprolide acetate started on day 22 of the previous cycle. Ten to twelve days later, the ovaries and uterus were scanned by TVU to exclude women with any abnormal structure in these organs. On the last day of the GnRH agonist treatment, a blood sample was taken to confirm that E2 serum levels were <100pmol/l and LH serum levels were 
3IU/l. Endometrial proliferation was then induced by the oral administration of micronized E2: 4mg/day on days 1–7 and 6mg/day on days 8–20. The endometrium was checked by TVU on day 14 to confirm adequate growth. Micronized progesterone, 600 mg/day, was administered from day 14 to 20 as follows: 400mg/day orally and 200mg/day vaginally. On day 20 (day 7 of progesterone administration), additional TVU was performed for endometrial assessment, and an endometrial biopsy was taken. These biopsies were performed as previously described for spontaneous cycles.
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A portion of each biopsy was immediately frozen in liquid nitrogen for subsequent RNA isolation. The remainder was transported in cold phosphate-buffered saline (PBS), placed in 30% sucrose in PBS overnight and subsequently embedded in OCT compound for immunohistochemistry, histological examination and dating by a pathologist according to Noyes et al. (1950).
RNA isolation
RNA extraction was performed according to a modification of the method of Chomczynski and Sacchi (1987), using Trizol reagent (Invitrogen, Carisbad, CA, USA). One millilitre of Trizol reagent was added for every 100mg of tissue. Total RNA was separated from DNA and protein by adding chloroform and was precipitated with isopropanol. The precipitate was washed with ethanol 75%, air-dried and resuspended in RNase–DNase free water. RNA was quantified by spectrophotometry on a SmartSpec 3000 spectrophotometer (Bio-Rad, Hercules, CA, USA). The 260/280 ratio varied between 1.8 and 1.9, and integrity was determined by the visual inspection of RNA fractionated by agarose gel electrophoresis. Each RNA sample was treated with DNase-I, (amplification grade, Invitrogen) to remove contaminating genomic DNA.
RT
All reagents used for RT were purchased from Invitrogen. RT was carried out at 46°C for 50min in a total volume of 20µl. Each reaction mixture contained 1µg of total RNA from endometrial tissue, 4µl of buffer 5x RT (250mM Tris–HCl, pH 8.3, 375mM KCl, 15mM MgCl2), 2µl of dithiothreitol (DTT) 0.1M, 10mM of mix dNTPs, 0.5µg of oligo (dT) primer and 200IU of SuperScript II reverse transcriptase. Reaction tubes were incubated at 46°C for 50min at the end of which reactions were stopped by heating at 70°C for 15min. Finally, RT products were treated with Ribonuclease H to remove mRNA for the second-strand cDNA synthesis.
Real time PCR
The relative expression of mRNA of MAO-A was determined using TaqMan® probes (Applied Biosystems, Foster City, CA, USA). The ABI PRISM 7900HT detection system (Applied Biosystems) and probes labelled with 5' FAM and 3' TAMRA (Molecular probes, Eugene, OR, USA) were used to determine the relative expression of MAO-A gene in all endometrial samples. Pre-synthesized primers and probe sets were used to determine the relative level of mRNA encoding human MAO-A (assay ID Hs00165140_m1, Assays-on-demand, Applied Biosystems). The endogenous glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA was assayed with reagents from the same source and was used as reference to normalize for differing amounts of starting material. Real time PCR assays were run using TaqMan Master Mix and the Applied Biosystems 7900HT Sequence Detection System. The thermal cycling conditions were 50°C for 2min, 95°C for 10min, followed by 45 cycles of 95°C for 15s and 60°C for 1min.
Quantitative analysis was based on the relative quantification of each gene of interest in the samples of each group using the ‘Delta-delta method’ developed by PE Applied Biosystems: 2[Ct (gene X in reference – gene X in endometrial samples)]– [Ct (GAPDH in reference – GAPDH in endometrial samples)] (Soong et al. 2001). Where Ct (Cycle thresholds) is the cycle in the amplification reaction in which the fluorescence begins to be exponential above the background base line and gene X corresponds to each gene of interest analysed.
Immunofluorescence
This technique was applied to endometrial samples obtained from four fertile women with spontaneous cycles, four subjects of group A and four of group B. After transportation in cold PBS, we transferred tissues to 10% w/v sucrose in PBS for 60min at 4°C followed by 30% w/v sucrose in PBS at 4°C for at least 1h. Frozen cryostat sections (4–6µm thick) were placed onto gelatin-coated slides. Sections were incubated with ammonium chlorine 100mM 45min to quench autofluorescence, followed by PBS washing and permeation in cold acetone for 10min. After rinsing in PBS three times, we blocked the sections with 10% rabbit normal serum in PBS for 90min. Sections were then washed three times with PBS and incubated overnight at 4°C with the primary polyclonal antibody against MAO-A from Santa Cruz Biotechnology (Santa Cruz, CA, USA), at a working dilution 1:25. Three PBS rinses were followed by incubation for 60min at room temperature with the secondary antibody rabbit anti-goat IgG conjugated with Alexa® Fluor 488 (Molecular Probes). After three PBS rinses, we counterstained the samples with 1µg/ml propidium iodide and mounted in 1,4-diazobicyclo-(2,2,2)-octane (DABCO) (Sigma, St Louis, MO, USA). The primary antibody was omitted as negative control, and sections of human placenta were used as positive control. The resulting staining was evaluated on a Carl Zeiss confocal laser scanning microscope. The label intensity was classified independently by two observers blinded to the slide identification as absent (–), weak (x), moderate (xx), medium (xxx) or strong (xxxx). Discrepancies were resolved by seeking consensus.
Analyses of data
Real time PCR data were analysed with the non-parametric Kruskal–Wallis test, followed by the Mann–Whitney test for pair-wise comparison when overall significance was detected. The immunofluorescence data were analysed using Fisher’s exact probability test. Statistical significance was set at P<0.05.
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Results |
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MAO-A mRNA levels in the endometrium during pre-receptive and receptive phase of normal spontaneous cycles
All cycles were ovulatory and exhibited normal endocrine profile, and all endometrial biopsy specimens taken from groups A and B were in phase according to Noyes criteria (Noyes et al., 1950
) (not shown). MAO-A mRNA levels on days LH+3 and LH+7 of six volunteers were analysed in triplicate using real time PCR. The data are shown in Figure 2 as a relative average value for MAO-A (median ± one quartile) normalized with the average value of the housekeeping gene GAPDH. The results confirm that MAO-A is expressed on both days examined and that MAO-A mRNA levels increase from LH+3 to LH+7 in all subjects examined, with a median increase of 25-fold (LH+3 
LH+7; P < 0.05).
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MAO-A mRNA levels in the endometrium during the luteal phase of induced cycles
Real time PCR was used to document MAO-A transcript levels in women who had been recipients in an oocyte donation program and normal fertile women. As shown on the right hand side of Figure 2, women in group A (no implantation) had endometrial MAO-A mRNA levels that were 29- and 6.8-fold lower during the receptive phase as compared with control groups B and C, respectively (A B P < 0.01; A C P < 0.05).
Expression and localization of MAO-A in the endometrium
MAO-A protein expression levels were determined by immunofluorescence in four samples taken during the luteal phase of spontaneous cycles. MAO-A green fluorescent staining was localized mainly to the luminal and glandular epithelium and scattered in the stromal compartment both on LH+3 and on LH+7 (Figure 3). Staining intensity increased significantly during the receptive phase (LH+7) in comparison with the pre-receptive period (LH+3) (Table I). The results of positive and negative controls (PC and NC, respectively in Figure 3) were as expected.
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Immunofluorescent labelling of MAO-A was detected only in a single sample from group A that displayed weak intensity (Table II). All samples from group B displayed strong fluorescence intensity comparable with that of samples from spontaneous cycles in LH+7 (Table II) (Figure 4).
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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The results presented herein confirm that MAO-A transcript levels increase in the human endometrium from the pre-receptive to the receptive phase, as previously reported using microarray analyses (Kao et al., 2002
; Borthwick et al., 2003; Riesewijk et al., 2003; Tapia-Pizarro et al., unpublished data). A concomitant increase was also observed in the level of MAO-A immunoreactive protein. Previous reports had also shown that MAO-A activity increases markedly in human endometrium during the mid-secretory phase of the menstrual cycle, coinciding with the period of endometrial receptivity (Ryder et al., 1980). Progesterone increases MAO-A activity in the rat uterus (Mazumder et al., 1980), and therefore, it is likely that it also increases MAO-A protein expression in the human endometrium, through progesterone response elements present in the promoter region of MAO-A gene (Borthwick et al., 2003). When the pattern of MAO-A expression was compared between groups A, B and C, a strong association was found between embryo implantation failure and decreased MAO-A transcript levels in all five subjects examined. Decreased MAO-A protein immunofluorescence was also associated with prior implantation failure in the four cases examined in group A. We cannot assume that these differences will persist when a healthy embryo is present and begins to interact with the endometrium. However, a critical difference is revealed at the molecular level between those women who failed repeatedly to obtain implantation and those who succeeded under the same procedures and conditions. Our experimental design was developed to assess endometrial gene expression associated with implantation failure under conditions in which an intrinsic defect in receptivity was the most likely cause.
Both MAO isoforms are present in the endometrium; however, only MAO-A levels change during the endometrial cycle, suggesting that its substrates or products are important for implantation. However, the function of MAO-A in endometrial physiology is unknown at present. Several years ago, it was proposed that MAO-A can improve the rate of implantation by inactivating 5-hydroxytryptamine, a potentially toxic molecule (Poulson et al., 1960). Microarray experiments (Kao et al., 2002; Borthwick et al., 2003; Riesewijk et al., 2003; Tapia-Pizarro et al., unpublished data) have identified several receptors for these biogenic amines whose role in endometrial physiology has not been established.
It is well known that monoamines are potent vasoactive agents and that the regulation of uterine blood flow is important throughout the endometrial cycle and during pregnancy when blood flow increases markedly. Reduced uterine blood flow due to sympathetic hyperactivity may be prevented by the partial inactivation of NE by MAO. The reported association between unexplained infertility and impairment of endometrial perfusion, assessed by Doppler ultrasound, is in keeping with this speculation (Chien et al., 2002; Edi-Osagie et al., 2004). However, MAO-A protein was found mainly in epithelial cells rather than capillaries and stromal cells, suggesting an alternate role for this enzyme. Beta adrenergic receptors are expressed in mouse preimplantation embryos, and the cell number in these embryos exposed to isoproterenol is lower than that in control embryos (Cikos et al., 2005), suggesting that low concentrations of beta adrenoreceptor agonists in uterine fluid may be required for normal embryo development. Because MAO-A is present in epithelial secretory cells, it may control beta adrenergic agonist concentrations in endometrial fluid.
The implantation requires a complex network of interactions with redundant mechanisms to ensure reproductive success. This complexity makes it difficult to identify critical genes and pathways involved in receptivity. On the basis of the present results, we believe that MAO-A is one of these critical genes. Lack of endometrial receptivity among infertile women in our study group is likely to be due to the poor expression of MAO-A and/or compromised expression of other genes regulated by MAO-A activity.
If MAO-A is a pivotal gene in implantation, it is a potential target for new strategies aimed at diagnosing and improving defective endometrial receptivity in infertile women. Further studies in a larger number of subjects should be performed to validate deficient levels of MAO-A expression in endometrial refractoriness to embryo implantation.
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Acknowledgements |
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We thank Dr Gareth Owen from Pontificia Universidad Católica de Chile for his critical reading of this manuscript. This study was made possible by funding from CONRAD CICCR project CIG 083-02 (L.V.); Supporting fellowship for Doctoral Thesis, 2002 CONICYT (A.T.); Fulbright-CONICYT fellowship (A.T.); Fondo Nacional de Desarrollo Cientifico y Tecnológico (FONDECYT 1030004) and with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-CO-12400 (Article H.36 of the Prime Contract). The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services nor does the mention of trade names, commercial products or organizations imply endorsement by the US Government.
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References |
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|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Bach A, Lan N, Johnson C, Abell A, Bembenek E, Kwan S, Seeburg P and Shih J (1988) cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 85,4934–4938.
Borthwick JM, Charnock-Jones DS, Tom BD, Hull ML, Teirney R, Phillips SC and Smith SK (2003) Determination of the transcript profile of human endometrium. Mol Hum Reprod 9,19–33.
Carson DD, Lagow E, Thathiah A, Al-Shami R, Farach-Carson MC, Vernon M and Lessey B (2002) Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening. Mol Hum Reprod 8,871–879.
Chien LW, Au HK, Chen PL, Xiao J, Tzeng CR and Tzeng CR (2002) Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 78,245–251.[CrossRef][Web of Science][Medline]
Chomczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162,156–159.[Web of Science][Medline]
Cikos S, Vesela J, Il’kova G, Rehak P, Czikkova S and Koppel J (2005) Expression of beta adrenergic receptors in mouse oocytes and preimplantation embryos. Mol Reprod Dev 71,145–153.[CrossRef][Web of Science][Medline]
Cohen S, Bitensky L and Chayen J (1965) The study of monoamine oxidase activity by histochemical procedures. Biochem Pharmacol 14,223–226.[CrossRef][Web of Science][Medline]
Crosignani PG, Collins J, Cooke ID, Diczfalusy E and Rubin B (1993) Recommendations of the ESHRE workshop on ‘Unexplained Infertility’. Hum Reprod 8,977–980.
Edi-Osagie EC, Seif MW, Aplin JD, Jones CJ, Wilson G and Lieberman BA (2004) Characterizing the endometrium in unexplained and tubal factor infertility: a multiparametric investigation. Fertil Steril 82,1379–1389.[CrossRef][Web of Science][Medline]
Johnston J (1968) Some observations upon a new inhibitor of monoamine oxidase in human brain. Biochem Pharmacol 17,1285–1297.[CrossRef][Web of Science][Medline]
Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA and Giudice LC (2002) Global gene profiling in human endometrium during the window of implantation. Endocrinology 143, 2119–2138.
Lessey BA (2000) The role of the endometrium during embryo implantation. Hum Reprod 15,39–50.
Martin J, Dominguez F, Avila S, Castrillo JL, Remohi J, Pellicer A and Simon C (2002) Human endometrial receptivity: gene regulation. J Reprod Immunol 55,131–139.[CrossRef][Web of Science][Medline]
Mazumder RC, Glover V and Sandler M (1980) Progesterone provokes a selective rise of monoamine oxidase A in the female genital tract. Biochem Pharmacol 29,1857–1859.[CrossRef][Web of Science][Medline]
Mirkin S, Arslan M, Churikov D, Corica A, Diaz JI, Williams S, Bocca S and Oehninger S (2005) In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum Reprod 20,2104–2117.
Noyes RN, Hertig AT and Rock J (1950) Dating the endometrial biopsy. Fertil Steril 1,3–25.[Medline]
Poulson E, Botros M and Robson JM (1960) Effect of 5-hydroxytryptamine and iproniazid on pregnancy. Science 131,1101–1102.
Riesewijk A, Martin J, Van Os R, Horcajadas JA, Polman J, Pellicer A, Mosselman S and Simon C (2003) Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Mol Hum Reprod 9,253–264.
Ryder TA, Mackenzie ML, Lewinsohn R, Pryse-Davies J and Sandler M (1980) Amine oxidase histochemistry of the human uterus during the menstrual cycle. Histochemistry 67,199–204.[CrossRef][Web of Science][Medline]
Shih JC and Thompson RF (1999) Monoamine oxidase in neuropsychiatry and behavior. Am J Hum Genet 65,593–598.[CrossRef][Web of Science][Medline]
Soong R, Beyser K, Basten O, Kalbe A, Rueschoff J and Tabiti K (2001) Quantitative reverse transcription-polymerase chain reaction detection of cytokeratin 20 in noncolorectal. lymph nodes. Clin Cancer Res 7(11), 3423–3429.
Southgate J, Grant EC, Pollard W, Pryse-Davies J and Sandler M (1968) Cyclical variations in endometrial monoamine oxidase: correlation of histochemical and quantitative biochemical assays. Biochem Pharmacol 17, 721–726.[CrossRef][Web of Science][Medline]
Sunder S and Lenton EA (2000) Endocrinology of the peri-implantation period. Baillieres Best Pract Res Clin Obstet Gynaecol 14,789–800.[CrossRef][Medline]
Valbuena D, Jasper M, Remohí J, Pellicer A and Simón C (1999) Ovarian stimulation and endometrial receptivity. Hum Reprod 14,107–111.
Submitted on July 11, 2006; resubmitted on August 30, 2006; accepted on September 7, 2006.
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