Biomedical subjects

Margarita Vega

Publications and source records attributed to Margarita Vega.

14 recordsLinked to original sources

PubMed2007

The biological standard of living (and its convergence) in Colombia, 1870-2003. A tropical success story.

During the 20th century, the evolution of the biological standard of living in Colombia was a tropical success story from the point of view of the secular increase in height as well as the reduction of inequality. During the period 1905-1985 the average height of females and males increased by nearly 9 cm on the basis of 9 million records examined from National Identification Cards. We also study the evolution of height of Colombians on the basis of passport records. The elite group of passport holders was much taller than average, and remained stable for the birth cohorts of 1870-1919. In the early 20th century the height of passport recipients was 168.7 cm (men) and 158 cm (women) compared with 162 cm and 150 cm for heights in the national ID cards. The results also show that Colombians experienced significant regional and intrapersonal convergence in height.

Body Height↗

PubMed2006

Sex hormone-binding globulin expression in the endometria of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the protein and messenger RNA expression of sex hormone-binding globulin (SHBG) in endometria from women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Thirty-three women with PCOS, and 17 fertile, healthy women of similar age to those with PCOS. INTERVENTION(S): Endometrial and blood samples were obtained from women with PCOS (PCOSEs) and from control women (CEs) during the proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies for SHBG (immunohistochemistry and reverse transcription-polymerase chain reaction). Hormonal studies for determining sex steroids (T, P, and E(2)) and SHBG concentration. Insulin sensitivity was assessed by composite insulin sensitivity index (ISI(composite)). RESULT(S): In stroma, the protein expression of SHBG was lower in PCOSEs than in CEs. Epithelial cells had a similar expression of SHBG protein in both groups. Messenger RNA of variant 548 base pairs (wild-type) tended to be lower in PCOSEs compared to CEs. When PCOSEs were classified by insulin resistance, the PCOSEs with normal insulin sensitivity showed an expression of stromal SHBG similar to that observed in CEs. CONCLUSION(S): The low SHBG expression in the stromal compartment of endometria from women with PCOS with insulin resistance may contribute to generate an abnormal steroid milieu in the endometria of these women.

Adult↗

PubMed2006

Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome.

OBJECTIVE: To evaluate gene and protein expression of steroid receptors, nuclear receptor coregulators, and uterine receptivity markers in midsecretory phase endometria from untreated women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Eight patients with PCOS and eight fertile women of similar age to those with PCOS. INTERVENTION(S): Endometrial samples were obtained from women with PCOS (PCOSE) and normal (NE) women during the midsecretory phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies (immunohistochemistry, reverse transcription-polymerase chain reaction [RT-PCR] and Western blot). RESULT(S): Endometria from PCOS exhibit higher levels of messenger RNA (mRNA) and protein for estrogen receptor alpha and coactivators than NE. Epithelial cells had a greater expression of progesterone receptor in PCOSE, whereas, no differences were observed in gene and protein expression of the nuclear corepressor (NcoR) and the antiadhesion molecule mucin type-1 (MUC-1) between PCOSE and NE. Immunodetection for the coactivator ARA70 was higher in PCOSE than in NE; in contrast, expression of beta3-integrin in epithelia was lower in PCOSE than in control endometria. CONCLUSION(S): The higher response to steroid hormones of endometria from untreated PCOS-women induces diminished expression of beta3 integrin, which partially explain implantation failure in PCOS patients.

Adult↗

PubMed2005

Augmented cell survival in eutopic endometrium from women with endometriosis: expression of c-myc, TGF-beta1 and bax genes.

BACKGROUND: Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes. METHODS: Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants. RESULTS: Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p < 0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p < 0.05). CONCLUSION: An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium.

Adult↗

PubMed2005

Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients.

OBJECTIVE: To evaluate the clinical response and endometrial morphology during the implantation window on ovarian hyperstimulation with the aromatase inhibitor letrozole in infertile ovulatory women. DESIGN: Prospective trial in infertile patients. SETTING: Tertiary care hospital. PATIENT(S): Eight ovulatory infertile patient candidates for ovarian superovulation. INTERVENTION(S): Subjects were monitored in one control cycle. In the next cycle, they received letrozole 5.0 mg daily on days 3 through 7 after menses. MAIN OUTCOME MEASURE(S): Number of ovulatory follicles; dominant follicle diameter; endometrial thickness; hormonal profile of FSH, LH, E(2), A, T, and P; endometrial histological dating; and pinopode formation assessed by scanning electron microscopy. RESULT(S): Cycles stimulated with letrozole resulted in more ovulatory follicles than did natural cycles (mean +/- SD 2.0 +/- 0.9 vs. 1.0 +/- 0.0), which attained a greater preovulatory diameter (mean +/- SD 23.8 +/- 2.7 vs. 19.3 +/- 2.1 mm), with similar endometrial thickness at midcycle compared with spontaneous cycles. Endocrine profile of medicated cycles was characterized on day 7 by increased levels of LH (5.9 +/- 0.8 vs. 3.5 +/- 0.4 IU/mL), reduced E(2) (98.4 +/- 11.4 vs. 161.5 +/- 14.7 pmol/L), and elevated androgens. Preovulatory and midsecretory E(2) were similar to spontaneous cycle, and P levels during midluteal phase were significantly elevated (44.2 +/- 4.6 vs. 27.7 +/- 4.6 pmol/L). Endometrial morphology during the implantation window in letrozole-stimulated cycles was characterized by in-phase histological dating and pinopode expression on scanning electron microscopy. CONCLUSION(S): Letrozole induces moderate ovarian hyperstimulation in ovulatory infertile patients with E(2) levels similar to spontaneous cycles and higher midluteal P, leading to both a normal endometrial histology and development of pinopodes, considered to be relevant markers of endometrial receptivity.

Adult↗

PubMed2005

Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clomiphene citrate.

OBJECTIVE: To assess the effect of clomiphene citrate (CC) on endometrial epithelial integrins and P receptors (PR) during the window of implantation. DESIGN: Controlled, prospective, clinical study. SETTING: Teaching hospital and university research laboratory. PATIENT(S): Thirty-one fertile, normo-ovulatory women participated in this trial. Thirteen women exhibited a CC-stimulated cycle with 50 mg on days 5-9, and 18 women with spontaneous menstrual cycles served as controls. INTERVENTION(S): Endometrial biopsies in the midluteal phase. MAIN OUTCOME MEASURE(S): Immunohistochemical determination and endometrial cellular localization of alpha1, alpha v, beta3, and alpha4 epithelial integrins and PR during the window of implantation. The staining intensity was assessed by a semiquantitative index (HSCORE) and compared by nonparametric Mann-Whitney test. RESULT(S): Higher plasma levels of P and E2 and delayed histologic dating of the endometrium (38%) were features of CC-treated women. In addition, a low epithelial beta3 integrin expression and persistent PR were observed in glandular epithelial cells of "out-of-phase" endometrial biopsies from CC-treated women. In contrast, in "in-phase" biopsies, neither epithelial PR nor beta3 integrin were different from spontaneous control cycles. There was no difference in the expression of alpha1, alpha v, and alpha4 between the groups studied. CONCLUSION(S): The administration of clomiphene produces aberrant endometrial beta3 integrin expression in conjunction with a failure in the down-regulation of PR during the window of implantation in a significant number of normo-ovulatory women, notwithstanding the higher plasma P levels. Therefore, CC might affect the expression of endometrial receptivity markers.

Adult↗

PubMed2004

Potential action of androstenedione on the proliferation and apoptosis of stromal endometrial cells.

BACKGROUND: Hyperandrogenic conditions have been associated with a high prevalence of endometrial pathologies related to cell survival. However, the action of androgens on proliferation and apoptosis in endometrial cells is poorly understood. Therefore, the aim of the present study was to evaluate the effect of androstenedione on cell proliferation, cell death and expression of estrogen receptor (ER) isoforms and proteins related to apoptosis in endometrial cells using two in vitro experimental approaches. METHODS: The endometrial tissue was obtained from 20 eumenorrheic women [28.7 (25 - 35) years] during the early secretory phase. We analyzed cell proliferation (immunohistochemistry of Ki-67 and spectrophotometric assay); apoptosis (DNA fragmentation (TUNEL) and Annexin V-FITC binding); ER-alpha, ER-beta bcl-2 and bax mRNA abundance (RT-PCR) in explants and isolated endometrial epithelial (EEC) and stromal cells (ESC) incubated with androstenedione 1 micro mol/l (A4) or A4 plus hydroxyflutamide 10 micro mol/l (F) for 24 h. RESULTS: In explants, A4 induced an increase of cell proliferation and a decrease on apoptosis in the stromal compartment (p < 0.05). In isolated ESC, proliferation augmented with A4 (p < 0.05), whereas, no significant modifications in the expression of ER-alpha, ER-beta bcl-2 and bax nor in the apoptotic index were observed. In EEC, A4 increase the ER-beta mRNA abundance (p < 0.05) and a decrease of the bcl-2/bax ratio (p < 0.05), without an increase in the apoptotic index. Hydroxyflutamide reverted the effect of androstenedione on the parameters described. CONCLUSIONS: These results indicate that androstenedione may modulate cell survival, expression of ER-beta and proteins related to apoptosis, suggesting a potential mechanism that associates the effect of hyperandrogenemia on the endometrial tissue.

Actins↗

PubMed2004

Differential in vitro actions of nitric oxide on human endometrial cell survival.

OBJECTIVE: To investigate the presence of caspase-3 and Bcl-2 concentration in human endometrial tissue throughout the menstrual cycle, and study the effect of nitric oxide (NO) on cell proliferation and apoptosis during culture. DESIGN: Expression of caspase-3 and Bcl-2 concentration in endometrial explants, and examination of L-arginine (L-Arg) effect on epithelial and stromal cell proliferation and apoptosis in vitro. SETTING: Prospective study.Twenty-seven eumenorrheic women (37 +/- 1.2 years). INTERVENTION(S): Endometrial samples were obtained with Pipelle suction curette from the corpus of the uterus. MAIN OUTCOME MEASURE(S): Apoptosis (annexin V-FITC binding), Bcl-2 concentration (ELISA), caspase-3 (immunohistochemistry), cell proliferation (spectrophotometric assay), and gene expression (RT-PCR). RESULT(S): Caspase-3 was detected by immunoassay in epithelial tissue throughout the menstrual cycle and in stroma during secretory phase. The Bcl-2 concentration was similar in endometrial homogenates obtained throughout the menstrual cycle, but L-Arg decreased Bcl-2 only in endometrium from the proliferative phase. In epithelial cells, NO increased apoptosis by 2.1 +/- 0.2-fold, augmented mRNA expression of Bax, and reduced expression of Bcl-2 compared with basal cultures. In stromal cells, NO increased cell proliferation in a dose-dependent manner, an effect that was blocked by a NO synthase inhibitor. CONCLUSION(S): These data indicate that NO has a differential regulatory function on endometrial cell survival, as indicated by the results on stromal cell proliferation and epithelial cell apoptosis during culture, which suggests paracrine interactions between both cell types.

Adult↗

PubMed2004

[P450Arom and estrogenic microenvironment of eutopic endometria in endometriosis].

BACKGROUND: Endometriosis, a common gynecologic disorder characterized by endometrial glands and stroma outside the uterus, is diagnosed by direct visualization of peritoneal and ovarian implants during laparoscopy. AIM: To study the estrogenic microenvironment in eutopic endometria of women with and without endometriosis. PATIENTS AND METHODS: Eutopic endometria, obtained during laparoscopy from 23 women with endometriosis and 20 fertile cyclic women undergoing tubal sterilization, was studied. P450Arom mRNA expression (RT-PCR) was measured. Also, P450Arom activity was assessed measuring testosterone conversion to estradiol and the concentration of this last hormone in cultured endometrial explants. RESULTS: Age and body mass index was similar in both groups studied. Seventy nine percent of endometria from women with endometriosis and in 29.4% from control group expressed P450Arom mRNA (p <0.01). The intensity of the band was higher in secretory endometria from women with endometriosis when compared to controls (p <0.01), but it was similar during the proliferative phase. Estradiol secretion to the culture media by proliferative endometria explants from women with endometriosis was 3-fold higher than secretory endometria (p <0.01) and endometria from control women in both phases. P450Arom activity, in the presence of testosterone, was 7-fold higher in endometrial cultures from women with endometriosis, when compare with the basal culture (p <0.01). However, in endometrial explant cultures from control women, this activity was not statistical different. CONCLUSIONS: These results indicate that in women with endometriosis, the microenvironment in the endometria is estrogenic as a consequence of an increased expression and activity of the P450Arom.

Aromatase↗

PubMed2003

Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the expression of steroid hormone receptors, proteins related to apoptosis, and cell proliferation in endometria from women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Eight women with PCOS and 12 fertile healthy women of similar age to those with PCOS. INTERVENTION(S): Endometrial samples were obtained from women with PCOS (PCOSE) and normal (NE) women during the proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies (immunohistochemistry and reverse transcription-polymerase chain reaction) and DNA fragmentation [TdT-mediated dUTP nick end labeling (TUNEL)]. RESULT(S): In stroma, protein expression of estrogen receptor alpha, Bcl-2, and Bax was higher in PCOSE than in NE; epithelial cells had a greater expression of androgen receptor in the nucleus and a lower expression in the cytoplasm of PCOSE. Cell proliferation was higher in the epithelia of NE, while the expression of caspase-3 and DNA fragmentation was similar in both groups. The bax mRNA expression was higher in PCOSE, and bcl-2 mRNA expression was similar between groups. A higher bcl-2/bax relative ratio in PCOSE was observed. CONCLUSION(S): An alternating expression of proteins related to cell survival in endometria from PCOSE may potentially be associated with the disruption of their endometrial cell cycle.

Adult↗

PubMed2002

Control of human luteal steroidogenesis.

The human corpus luteum (CL) undergoes a dynamic cycle of differentiation, steroid hormone production and regression during the course of non-fertile cycles. In humans and other primates, luteal steroidogenesis is absolutely dependent on pituitary-derived LH. However, changes in LH and LH receptor expression do not explain the marked decline in progesterone production at the end of the luteal phase. Changes in the level of the steroidogenic acute regulatory protein (StAR), a gene whose expression is controlled by LH most likely account for the cyclic pattern of progesterone production. During the mid-to-late luteal phase of a fertile cycle, chorionic gonadotropin (hCG) rescues the CL, overcoming the actions of the factors inducing luteolysis. Although the agents causing regression of the CL in a non-fertile cycle are not yet known, intra-luteal growth factors and cytokines that modify the action of LH probably contribute to the reduction of StAR expression and the subsequent fall in progesterone production.

3-Hydroxysteroid Dehydrogenases↗

PubMed2002

Role of nitric oxide and bcl-2 family genes in the regulation of human endometrial apoptosis.

OBJECTIVE: To investigate the role of nitric oxide (NO) and death regulatory genes, bcl-2 and bax, in human endometria apoptosis. DESIGN: Expression of bcl-2, bax, NO synthases (NOS), and the apoptotic effect of L-arginine on endometrial explants in vitro. SETTING: Prospective study. PATIENT(S): Thirty-seven eumenorrheic women. INTERVENTION(S): Endometrial samples were obtained with Pipelle suction curette after women signed institutional informed consent forms. MAIN OUTCOME MEASURE(S): DNA fragmentation (TUNEL), immunohistochemistry, and reverse transcription polymerase chain reaction. RESULT(S): Apoptosis was detected in mid and late secretory endometria. L-arginine induced an increase in apoptosis in stroma (threefold), glands (eightfold), and surface epithelia (fourfold) in proliferative but not secretory endometria explants. Immunostaining of Bcl-2 was almost absent in the secretory endometria, whereas Bax increased in the stroma at the end of the menstrual cycle, coincident to the decrease in the bcl-2/bax mRNA relative ratio (P<.05) observed in secretory endometria. CONCLUSION(S): The induction of DNA fragmentation by L-arginine on proliferative endometria suggests that NO may be involved in the endometrial apoptotic process, whose control may be related predominantly to the changes of Bcl-2 expression.

Adult↗

PubMed2001

Luteal phase support.

Assisted reproductive techniques have become a routine treatment for infertility. The extended use of gonadotrophin-releasing hormone analogues in assisted reproductive techniques has made luteal phase support mandatory, as it has been clearly demonstrated that they alter luteal LH pulsatility. For luteal support, HCG administration, though effective, has a high risk of ovarian hyperstimulation syndrome. Progesterone continues to be the gold standard for supplementation. Vaginal progesterone represents a highly effective alternative to painful intramuscular injections. The vaginal route is mainly characterized by direct delivery of the progesterone to the endometrium, thus producing high levels at the target tissue and a very low incidence of side effects.

Journal Article↗

PubMedDate not supplied

Molecular regulation of progesterone secretion by the human corpus luteum throughout the menstrual cycle.

The present study examines the expression of the steroidogenic acute regulatory protein (StAR) within the human corpus luteum (CL) in conjunction with other molecules that regulate the apoptotic process of the CL. Our results indicate that the primary 1.6 kb StAR transcript occurs in greater abundance in early and mid-luteal phase compared with late luteal phase CL. Mature StAR protein (30 kDa) was present in lower amounts within late CL compared with early and mid-luteal phase. The pre-protein (37 kDa), which has been considered the active isoform to favor cholesterol translocation and subsequently steroid hormone synthesis, was also detected in lower amount in late CL. Several molecules, including pro-inflammatory cytokines, reactive oxygen species, steroids and inducible nitric oxide synthase (iNOS), have been linked as pro-apoptotic regulatory agents. Moreover, many of these molecules diminish progesterone synthesis in human cultured luteal cells. Interestingly, these molecules preferentially decrease progesterone biosynthesis in mid and late luteal cells in culture. These data suggest that the inhibitory effect of these molecules, as well as the amount of apoptotic cells in the CL are age dependent. The number of luteal apoptotic cells, as well as luteal cells stained positive for iNOS, increased from early to late CL. To examine the effects of hCG on StAR expression and apoptosis, we used two models-(1) in vivo hCG administration during the late luteal phase; and (2) in vitro incubation of explants of late CL with hCG. hCG increased both the level of StAR expression and the level of anti-apoptotic protein Bcl-2 within the late CL. We conclude that mRNA and protein expression of StAR and bcl-2 are important target elements for hCG during the CL rescue.

Adult↗