Expression and hormonal regulation of Muc-1 at the apical surface of mouse uterine epithelial cells and its role in modulating embryo implantation

Previous studies from our lab have established that large molecular weight mucin glycoproteins are major apically-disposed components of mouse uterine epithelial cells in vitro (Valdizan et al., (1992) J. Cell. Physiol. 151:451-465). The present studies demonstrate that Muc-1 represents one of the apically-disposed mucin glycoproteins of mouse uterine epithelia, and that Muc-1 protein and mRNA expression are regulated in the peri-implantation stage mouse uterus by ovarian steroids. Muc-1 expression is high in the proestrous and estrous stages, and decreases during diestrous. Both Muc-1 protein and mRNA levels decline to barely detectable levels by day 4 of pregnancy, i.e., prior to the time of blastocyst attachment. In contrast, Muc-1 expression in the cervix and vagina is maintained during this same period. Delayed implantation was established in pregnant mice by ovariectomy and maintained by administration of exogenous progesterone. Initiation of implantation was triggered by coinjection of progesterone maintained mice with a nidatory dose of 17$\beta$-estradiol. Muc-1 levels in the uterine epithelia of progesterone maintained mice declined to similar low levels as observed on day 4 of normal pregnancy. Coinjection of estradiol did not alter Muc-1 expression suggesting that down-regulation of Muc-1 is a progesterone dominated event. This was confirmed in ovariectomized, non-pregnant mice which displayed stimulation of Muc-1 expression following 6 hr of estradiol injection. Estradiol stimulated Muc-1 expression was inhibited by the pure antiestrogen, ICI 164,384. While progesterone alone had no effect on Muc-1 expression, it antagonized estradiol action in this regard. Injection of pregnant mice with the antiprogestin, RU 486, a known implantation inhibitor, on day 3 of pregnancy restored high level expression of Muc-1 mRNA on day 4, indicating that down-regulation of Muc-1 is progesterone receptor-mediated. Muc-1 appears to function as an anti-adhesive molecule at the apical cell surface of mouse uterine epithelial cells. Treatment of polarized cultures of mouse uterine epithelial cells with O-sialoglycoprotein endopeptidase reduced mucin expression in vitro, by about 50%, and converted polarized uterine epithelia to a functionally receptive state. Similarly, ablation of Muc-1 in Muc-1 null mice resulted in polarized uterine epithelia that were functionally receptive as compared to their wild-type counterparts in vitro. Collectively, these data indicate that Muc-1 and other mucins function as anti-adhesive molecules and that reduction or removal of these molecules is a prerequisite for the generation of a receptive uterine state. ^

An investigation of the pica practices of pregnant women in Houston and Prairie View, Texas

Pregnant African American women are at higher risk of having a preterm delivery and/or a low birthweight infant. Many factors are associated with adverse pregnancy outcomes but a food habit that deserves further study in the causal process is pica, a craving for, and ingestion of, nonnutritive substances such as laundry starch, clay, dirt, or ice. This food habit is more common in the African American population but has not been adequately studied in relation to preterm and/or low birth weight infants.^ Mothers (n = 281) with infants less than one year of age who participated in the Special Supplementary Food Program for Women, Infants, and Children (WIC) at clinics in Houston and Prairie View, Texas were interviewed regarding pica practices during pregnancy, dietary practices, and some demographic indices. Hospital records were abstracted for health information on the mothers and infants, including birthweight and gestational age at birth of the infant.^ The subjects were 88.6% African American, 6.8% Hispanic, and 4.6% Caucasian. Overall prevalence of pica was 76.5%. Pica prevalence by substance(s) was as follows: ice 53.7%; ice and freezer frost 14.6%; other substances such as baking soda, baking powder, cornstarch, laundry starch, and clay or dirt 8.2%; and 23.5% reported no pica. The women who reported ice/freezer frost pica had a higher percentage of illegal drug use and alcohol use during pregnancy. The women who reported other pica substances had the lowest mean educational level, highest gravidity, and a higher percentage smoked during pregnancy.^ There were no significant differences in nutrient intakes measured by the mean 24-hour dietary recalls between women who reported ice pica (n = 103) and women who denied pica (n = 50). The women who reported ice/freezer frost pica or other pica substances had more food cravings and food dislikes during pregnancy than those who reported ice pica or no pica.^ There were no differences in mean birthweight or mean gestational age at birth of infants born to mothers from the three pica groups and the no pica group but regression analyses revealed a possible relationship between pica, low maternal hemoglobin at delivery, and preterm birth. ^

Patterns of care and outcomes for pregnant inmates and their infants in Texas state prisons: Epidemiologic and ethnographic analyses

Female inmates make up the fastest growing segment in our criminal justice system today. The rapidly increasing trend for female prisoners calls for enhanced efforts to strategically plan the correctional facilities that address the needs of this growing population, and to work with communities to prevent crime in women. The incarcerated women in the U.S. have an estimated 145,000 minor children who are predisposed to unique psychosocial problems as a result of parental incarceration.^ This study examined the patterns of care and outcomes for pregnant inmates and their infants in Texas state prisons between 1994 and 1996. The study population consists of 202 pregnant inmates who delivered in a 2-year period, and a randomly sampled comparison cohort of 804 women from general Texas population, matched on race and educational levels. Both quantitative and qualitative data were used to elucidate the inmates' risk-factor profile, delivery/birth outcomes, and the patterns of care during pregnancy. The continuity-of-care issues for this population were also explored.^ Epidemiologic data were derived from multiple record systems to establish the comparison between two cohorts. A significantly great proportion of the inmates have prior lifestyle risk-factors (smoking, alcohol, and illicit drug abuse), poorer health status, and worse medical history. However, most of these existing risk-factors seem to show little manifestation in their current pregnancy. On the basis of maternal labor/delivery outcome and a number of neonatal indicators, this study found some evidence of a better pregnancy outcome for the inmate cohort when compared to the comparison group. Some possible explanations of this paradox were discussed. Seventeen percent of inmates gave birth to infants with suspected congenital syphilis. The placement patterns for the infants' care immediately after birth were elucidated.^ In addition to the quantitative data, an ethnographic approach was used to collect qualitative data from a subset of the inmate cohort (n = 20) and 12 care providers. The qualitative data were analyzed for their contents and themes, giving rise to a detailed description of the inmates' pregnancy experience. Eleven themes emerged from the study's thematic analysis, which provides the context for interpreting the epidemiologic data.^ Meaningful findings in this study were presented in a three-dimensional matrix to shed light on the apparent relationship between outcome indicators and their potential determinants. The suspected "linkages" between the outcome and their determinants can be used to generate hypotheses for future studies. ^

Prenatal care content and utilization among pregnant women enrolled in managed care programs in Harris County, Texas

This research study was conducted as a descriptive study of prenatal care experiences of women enrolled in public and private managed care programs. The study's aim was to describe the demographic characteristics of the women in the study and to analyze and compare their prenatal care experiences. ^ The objective of this study was to examine the research question: Do pregnant women enrolled in Medicaid Managed Care receive the same level of care as women enrolled in other Managed Care Programs in Harris County, Texas? ^ The study population was a convenience sample of pregnant women enrolled in managed care programs who presented to one of the two hospital study sites for delivery of their infant. The study utilized a self administered survey to measure adequacy and content of prenatal care received by the women during this pregnancy. Adequacy of prenatal care utilization was determined based on the Kessner Index criteria of timing of initiation of care and number of visits. Content of care was measured by the number of different medical services the women reported they had received and the number of health information topics the women reported on which they had received information. Demographic characteristics were described with univariate and bivariate statistics of frequencies and cross tabulations. Associations were evaluated using measures of linear correlations. ^ Results from the study showed there is an association between enrollment in Medicaid Managed Care (public) and prenatal care received compared to women enrolled in other Managed Care Programs (private). The results were derived from statistical tests on data the postpartum women gave when they completed the self-administered survey. Provider type was a moderate predictor of quality and quantity of prenatal care. The results also indicate that in the study population, minority ethnicity, income and lower educational status were associated with intermediate and inadequate prenatal care. ^

Hepatitis B vaccination of high risk pregnant women: A clinical trial at Parkland Memorial Hospital

Hepatitis B infection is a major public health problem of global proportions. It is estimated that 2 billion people worldwide are infected by the Hepatitis B virus (HBV) at some point, and 350 million are chronic carriers. The Centers for Disease Control and Prevention (CDC) report an incidence in the United States of 140,000–320,000 infections each year (asymptomatic and symptomatic), and estimate 1–1.25 million people are chronically infected. Hepatitis B and its chronic complications (cirrhosis of the liver, liver failure, hepatocellular carcinoma) responsible for 4,000–5,000 deaths in America each year. ^ One quarter of those who become chronic carriers develop progressive liver disease, and chronic HBV infection is thought to be responsible for 60 million cases of cirrhosis worldwide, surpassing alcohol as a cause of liver disease. Since there are few treatment options for the person chronically infected with Hepatitis B, and what is available is expensive, prevention is clearly best strategy for combating this disease. ^ Since the approval of the Hepatitis B vaccine in 1981, national and international vaccination campaigns have been undertaken for the prevention of Hepatitis B. Despite encouraging results, however, studies indicate that prevalence rates of Hepatitis B infection have not been significantly reduced in certain high risk populations because vaccination campaigns targeting those groups do not exist and opportunities for vaccination by individual physicians in clinical settings are often missed. Many of the high-risk individuals who go unvaccinated are women of childbearing age, and a significant proportion of these women become infected with the Hepatitis B virus (HBV) during pregnancy. Though these women are often seen annually or for prenatal care (because of the close spacing of their children and their high rate of fertility), the Hepatitis B vaccine series is seldom recommended by their health care provider. In 1993, ACOG issued a statement recommending Hepatitis B vaccination of pregnant women who were defined as high-risk by diagnosis of a sexually transmitted disease. ^ Hepatitis B vaccine has been extensively studied in the non-pregnant population. The overall efficacy of the vaccine in infants, children and adults is greater than 90%. In the small clinical trials to date, the vaccine seemed to be effective in those pregnant women receiving 3 doses; however, by using the usual 0, 1 and 6 month regimen, most pregnant women were unable to complete a full series during pregnancy. There is data now available supporting the use of an "accelerated" dosing schedule at 0, 1 and 4 months. This has not been evaluated in pregnant women. A clinical trial proving the efficacy of the 0, 1, 4 schedule and its feasibility in this population would add significantly to the body of research in this area, and would have implications for public health policy. Such a trial was undertaken in the Parkland Memorial Hospital Obstetrical Infectious Diseases clinic. In this study, the vaccine was very well tolerated with no major adverse events reported, 90% of fully vaccinated patients achieved immunity, and only Body Mass Index (BMI) was found to be a significant factor affecting efficacy. This thesis will report the results of the trial and compare it to previous trials, and will discuss barriers to implementation, lessons learned and implications for future trials. ^

The association between uterus shape and development of chronic conditions in a retrospective corhort of diethylstilbestrol-exposed women in Minnesota and Texas

Diethylstilbestrol (DES) exposed women are well known to be at increased risk of gynecologic cancers and infertility. Infertility may result from DES associated abnormalities in the shape of women's uteri, yet little research has addressed the effect of uterine abnormalities on risk of infertility and reproductive tract infection. Changes in uterine shape may also influence the risk of autoimmune disease and women's subsequent mental health. A sample of consenting women exposed in utero to hormone who were recruited into the DESAD project, underwent hysterosalpingogram (HSG) from 1978 to 1984. These women also completed a comprehensive health questionnaire in 1994 which included women's self-reports of chronic conditions. HSG data were used to categorize uterine shape abnormalities as arcuate shape, hypoplastic, wide lower segment, and constricted. Women were recruited from two of the four DESAD study sites in Houston (Baylor) and Minnesota (Mayo). All women were DES-exposed. Adjusted relative risk estimates were calculated comparing the range of abnormal uterine shaped to women with normal shaped uteri for each of the four outcomes: infertility, reproductive tract infection, autoimmune disease and depressive symptoms. Only the arcuate shape (n=80) was associated with a higher risk of infertility (relative risk [RR]= 1.53, 95% CI = 1.09, 2.15) as well as reproductive tract infection (RR= 1.74, 95% CI = 1.11, 2.73). In conclusion, DES-associated arcuate shaped uteri appeared to be associated with the higher risk of a reproductive tract infection and infertility while no other abnormal uterine shapes were associated with these two outcomes.^

Evaluation of web-based resources for pregnant and parenting teens

Current teen pregnancy and repeat pregnancy rates reveal that there is a pressing need for comprehensive care for pregnant and parenting teens to address their unique needs. The Internet has become a source of various types of information and as a result, several efforts have begun to assess the quality of health information provided on websites. The objective of this study was to assess the functionality and quality of websites containing health information and resources for pregnant and parenting teens. The three most widely used search engines currently: Google, MSN, and Yahoo were searched using three general search terms “teen pregnancy”, “pregnant teen”, and “teen parent”. The first 5 pages of each search were reviewed and categorized to yield 12 websites which met inclusion criteria for content evaluation. The 12 websites were rated using a pre-existing instrument encompassing two domains: functionality and content analysis. Within the functionality domain, this sample highlighted the need to improve accessibility and credibility for the target population. The content analysis revealed that among the topics which are recommended for pregnant and parenting teens, the topics most commonly covered were mental health and primary and preventive health care. The majority of websites neglected sexual health topics including STI’s and family planning. This study provides the first glimpse into health information and resources for pregnant and parenting teens on the Internet. Researchers, health care providers, social workers, health educators, and website sponsors can use these results to maintain and recommend websites which offer easily accessible, accurate, and practical information for pregnant and parenting teens.^

Systematic review of acceptance of the influenza vaccine among pregnant women

Exposure to influenza places pregnant women at risk for pneumonia and their fetus at risk for premature delivery or fatal stillbirth secondary to maternal hypoxia. Immunization rates are low among pregnant women. Influenza vaccine specific-health belief model constructs, such as cue to action messages from the health care professionals, may increase acceptance of the vaccine and improve immunization rates. A systematic review was conducted to evaluate the impact of physician recommendation upon acceptance of the influenza vaccine by pregnant women. Pregnant women were more likely to accept the influenza vaccine if they received a recommendation from their physician. These women were also more likely to accept the vaccine if they thought the vaccine protected mother and fetus against adverse effects of influenza and were less likely to accept the vaccine if they were concerned about side effects or risk to the fetus from the vaccine.^

A descriptive study of comprehensive and categorical services for pregnant and parenting adolescents in West Dallas

This study evaluates the effectiveness of the Children and Youth Projects' Adolescent Family Life Program, a comprehensive program serving pregnant and parenting adolescents in the economically disadvantaged area of West Dallas. The underlying question asked is what are the relative contributions of the comprehensive, school-linked Adolescent Family Life (AFL) Program compared with the Maternal Health and Family Planning Program (MHFPP), a categorical provider of family planning and reproductive services, towards meeting the immediate and intermediate term needs of adolescent mothers. Also addressed are the protective effects of participation in the Dallas Independent School District Health Special Program, a segregated school for pregnant adolescents.^ A cohort of 339 West Dallas adolescent mothers who delivered babies during a two-year period, 1986 through 1987, are monitored by linking records from Parkland Hospital, the primary provider to hospital services to indigent women in Dallas, the Dallas Independent School District, and the prenatal care providers, the AFL and MHFP Programs. Information is collected on each teen describing her demographic, fertility, service utilization and educational characteristics.^ The study tests the hypothesis that adolescents receiving services from the comprehensive AFL program will be less likely to have a repeat birth and to discontinue school during the 24 month study period, compared with categorical provider clients. Although the study finds that there are no statistically significant differences in repeat deliveries, using survival analysis, or in school continuation between programs, important findings are revealed about the ethnic differences. Black and Hispanic fertility and educational behaviors are compared, and their implications for program design and evaluation discussed. ^

Planning, implementation, and evaluation of an HIV -screening program for pregnant women

The purpose of this study was to evaluate the effectiveness of an HIV-screening program at a private health-care institution where the providers were trained to counsel pregnant women about the HIV-antibody test according to the latest recommendations made by the U.S. Public Health Service (PHS) and the Texas legislature. A before-and-after study design was selected for the study. The participants were OB/GYN nurses who attended an educational program and the patients they counseled about the HIV test. Training improved the nurses' overall knowledge about the content of the program and nurses were more likely to offer the HIV test to all pregnant women regardless of their risk of infection. Still, contrary to what was predicted, the nurses did not give more information to increase the knowledge pregnant women had about HIV infection, transmission, and available treatments. Consequently, many women were not given the chance to correctly assess their risk during the counseling session and there was no evidence that knowledge would reduce the propensity of many women to deny being at risk for HIV. On the other hand, pregnant women who received prenatal care after the implementation of the HIV-screening program were more likely to be tested than women who received prenatal care before its implementation (96% vs. 48%); in turn, the likelihood that more high-risk women would be tested for HIV also increased (94% vs. 60%). There was no evidence that mandatory testing with right of refusal would deter women from being tested for HIV. When the moment comes for a woman to make her decision, other concerns are more important to her than whether the option to be tested is mandatory or not. The majority of pregnant women indicated that their main reasons for being tested were: (a) the recommendation of their health-care provider; and (b) concern about the risks to their babies. Recommending that all pregnant women be tested regardless of their risk of infection, together with making the HIV test readily available to all women, are probably the two best ways of increasing the patients' participation in an HIV-screening program for pregnant women. ^

Regulation of phosphatidylinositide turnover in the myometrium by cAMP: Implications for the control of uterine contraction

Regulation of uterine quiescence involves the integration of the signaling pathways regulating uterine contraction and relaxation. Uterine contractants increase intracellular calcium through receptor/GαqPLC coupling, resulting in contraction of the myometrium. Elevation of cAMP concentration has been correlated with relaxation of the myometrium. However, the mechanism of cAMP action in the uterus is unclear. ^ Both endogenous and exogenous increases in cAMP inhibited oxytocin-stimulated phosphatidylinositide turnover in an immortalized pregnant human myometrial cell line (PHM1-41). This inhibition was reversed by cAMP-dependent protein kinase (PKA) inhibitors, suggesting the involvement of PKA. cAMP inhibited phosphatidyinositide turnover stimulated by different agonists in different cell lines. These data suggest that the cAMP inhibitory mechanism is neither cell nor receptor dependent, and inhibits Gαq/PLCβ1 and PLCβ3 coupling. ^ The subcellular localization of PKA occurs via PKA binding to A-Kinase-Anchoring-Proteins (AKAP), and peptides that inhibit this association have been developed (S-Ht31). S-Ht31 blocked cAMP-stimulated PKA activity and decreased PKA concentration in PHM1-41 cell plasma membranes. S-Ht31 reversed the ability of CPT-cAMP, forskolin and relaxin to inhibit phosphatidylinositide turnover in PHM1-41 cells. Overlay analysis of both PHM1-41 cell and nonpregnant rat myometrium found an AKAPs of 86 kDa and 150 kDa associated with the plasma membrane, respectively. These data suggest that PKA anchored to the plasma membrane via AKAP150/PKA anchoring is involved in the cAMP inhibitory mechanism. ^ CPT-cAMP and isoproterenol inhibited phosphatidylinositide turnover in rat myometrium from days 12 through 20 of gestation. In contrast, neither agent was effective in the 21 day pregnant rat myometrium. The decrease in the cAMP inhibitory mechanism was correlated with a decrease in PKA and an increase in protein phosphatase 2B (PP2B) concentration in rat myometrial plasma membranes on day 21 of gestation. In myometrial total cell homogenates, both PKA and PP2B concentration increased on day 21. S-Ht31 inhibited cAMP inhibition of phosphatidylinositide turnover in day 19 pregnant rat myometrium. Both PKA and PP2B coimmunoprecipitated with an AKAP150 in a gestational dependent manner, suggesting this AKAP localizes PKA and PP2B to the plasma membrane. ^ These data presented demonstrate the importance of the cAMP inhibitory mechanism in regulating uterine contractility. ^

Attitudes of health-care workers toward pregnant, HIV -positive women

The management of HIV infection with antiretroviral drugs has succeeded in increasing survival rates, but the subject of pregnancy in HIV-positive women continues to garner debate. Discrimination and stigma have been identified as barriers to health care, suggesting that women with HIV may be disinclined to seek prenatal care if health-care workers exhibit negative attitudes toward the women's pregnancies. To optimize prenatal and medical care for women with HIV infection, it is important to understand the general social conditions and cultural context in which these women have children. Goffman's treatise on stigma, Foucault's discussion of the knowledge/power matrix, and Bandura's Social Cognitive Theory offer theoretical perspectives by which we can evaluate the gender, race, and class issues that are inherent in pregnancy decision-making for women with HIV infection. It is also necessary to evaluate prevailing attitudes on childbearing toward HIV-positive women and to review the historical background of prejudice in which HIV-positive women make decisions regarding childbearing. ^ This qualitative study used a survey instrument and one-on-one interviews with HIV-infected women to elicit their perceptions of how they were treated by care providers when they became pregnant. It also included interviews with health-care workers to determine what their feelings are about pregnancy within the context of HIV infection. Results of the ethnographic inquiry reveal that most of the women had negative experiences at some point during a pregnancy, but that the situation improved when they sought care from a provider who was familiar with HIV infection. The health-care providers interviewed were firm in their belief that HIV-positive women deserved optimal care and treated the women with respect, but these are individuals who are also experts in providing care to HIV-positive patients. The question remains as to what kind of care HIV-positive women are receiving generally and what types of attitudes they are being subjected to if they see less experienced providers. Further research is also needed to determine whether HIV-positive women from a broader ethnic representation and higher socioeconomic status experience similar negative attitudes. ^