Michelle R. Meyer

Perivascular Human Endometrial Mesenchymal Stem Cells Express Pathways Relevant to Self-Renewal, Lineage Specification, and Functional Phenotype

ABSTRACT Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)+/PDGFRB+ (eMSC), MCAM (CD146)−/PDGFRB+ (fibroblast), and MCAM (CD146)+/PDGFRB− (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast.

Coculturing human endometrial epithelial cells and stromal fibroblasts alters cell-specific gene expression and cytokine production

OBJECTIVE To determine the effects of coculturing endometrial epithelial cells (eEC) with paired endometrial stromal fibroblasts (eSF) on cell-specific gene expression and cytokine secretion patterns. DESIGN In vitro study. SETTING University research laboratory. PATIENT(S) Endometrial biopsies were obtained from premenopausal women. INTERVENTION(S) Polarized eEC and subject-paired eSF were cultured for 12.5 hours alone (monoculture) or combined in a two-chamber coculture system without cell-cell contact. Cells and conditioned media were analyzed for global gene expression and cytokine secretion, respectively. Purified, endometrial tissue-derived eEC and eSF isolated by fluorescent activated cell sorting (FACS) were used as noncultured controls. MAIN OUTCOME MEASURE(S) Cell-specific global gene expression profiling and analysis of secreted cytokines in eEC/eSF cocultures and respective monocultures. RESULT(S) Transepithelial resistance, diffusible tracer exclusion, expression of tight junction proteins, and apical/basolateral vectorial secretion confirmed eEC structural and functional polarization. Distinct transcriptomes of eEC and eSF were consistent with their respective lineages and their endometrial origin. Coculture of eEC with eSF resulted in altered cell-specific gene expression and cytokine secretion. CONCLUSION(S) This coculture model provides evidence that interactions between endometrial functionally polarized epithelium and stromal fibroblasts affect cell-specific gene expression and cytokine secretion underscoring their relevance when modeling endometrium in vitro.

Prospective risk of fetal death with gastroschisis.

Abstract Objective: To evaluate the ongoing risk of intrauterine fetal demise (IUFD) in fetuses with gastroschisis compared to non-anomalous fetuses. Methods: This was a retrospective cohort study of all births in the United States in 2005–2006, as recorded in the National Center for Health Statistics natality database. Risk of IUFD in fetuses with gastroschisis was compared to non-anomalous fetuses, utilizing total at-risk fetuses as the denominator. Results: Risk of IUFD in fetuses with gastroschisis was 4.5%, compared to 0.6% in non-anomalous fetuses (p < 0.001). When controlling for gestational age and other confounders, the adjusted odds ratio for IUFD in fetuses with gastroschisis was 7.06 (95% CI: 3.33–14.96). After 32 weeks, risk of IUFD/ongoing pregnancy was greater at each week of gestation in fetuses with gastroschisis. Conclusions: Risk of IUFD for fetuses with gastroschisis is greater than in non-anomalous fetuses. This risk increases significantly after 32 weeks’ gestation. Demographic variables are associated with higher rates of gastroschisis and ultimately IUFD. These data may be useful in consideration of timing of delivery.

Racial/ethnic variations in perineal length and association with perineal lacerations: a prospective cohort study.

Abstract Objective: To examine the association between race/ethnicity, perineal length and the risk of perineal laceration. Methods: This is a prospective cohort study of a diverse group of women with singleton gestations in the third trimester of pregnancy. Perineal length was measured and mean values calculated for several racial/ethnic groups. Chi-squared analyses were used to examine rates of severe perineal laceration (third or fourth degree laceration) by race/ethnicity among women considered to have a short perineal length. Further, subgroup analyses were performed comparing nulliparas to multiparas. Results: Among 344 study participants, there was no statistically significant difference in mean perineal length by race/ethnicity (White 4.0 ± 1.1 cm, African-American 3.7 ± 1.0 cm, Latina 4.1 ± 1.1 cm, Asian 3.8 ± 1.0 cm, and other/unknown 4.0 ± 0.9 cm). Considering parity, more multiparous Asian and African-American women had a short perineal length (20.7 and 23.5%, respectively, p = 0.05). Finally, the rate of severe perineal lacerations in our cohort was 2.6% overall, but was 8.2% among Asian women (p = 0.04). Conclusions: We did not find a relationship between short perineal length and risk of severe perineal laceration with vaginal delivery, or a difference in mean perineal length by maternal race/ethnicity. However, we did find that women of different racial/ethnic groups have varying rates of severe perineal laceration, with Asian women comprising the highest proportion.

Preference toward future mode of delivery: how do antepartum preferences and prior delivery experience contribute?

Abstract Objective: Examine postpartum preferences toward future mode of delivery (MOD), considering recent MOD, antepartum preferences, and demographics. Study design: Prospective cohort study where a survey was distributed in outpatient obstetrics clinics to pregnant women over 18 years at 28 weeks gestation or later. Surveys gathered demographics, obstetric history, and preference toward vaginal delivery (VD) versus cesarean delivery (CD). Women were again surveyed at 6–8 weeks postpartum. Chi-square test compared proportions, and logistic regression controlled for potential confounders. Results: A total of 299 women returned postpartum surveys and expressed preferences. Comparing women who experienced VD versus CD, the majority who had a VD (92.1%) would choose this again, while only 1.9% preferred CD. Among the CD group, preferences were mixed: 29.4% desired repeat CD, 34.1% preferred VD, and 36.5% were undecided (p < 0.001). Adjusted odds were 34.4 (95% CI 9.4–126.1) for preferring VD over CD among women who experienced a recent VD, adjusting for parity, age, ethnicity, education, possible depression, and type of provider. Conclusions: The majority of women preferred VD postpartum. Of the minority who desired CD, antenatal preference for cesarean and prior experience with CD were important factors. This highlights the impact of individual desires and experience, and underscores importance of antenatal counseling.

How do maternal views of delivery outcomes vary by demographics and preferred mode of delivery

OBJECTIVE To investigate how maternal views of delivery outcomes vary by demographic characteristics and preference toward mode of delivery (MOD). STUDY DESIGN Survey of 719 pregnant women in outpatient clinics at an academic institution during their third trimester. Women ranked outcomes such as vaginal delivery (VD), cesarean delivery (CD), urinary incontinence, perineal lacerations, and induction of labor (IOL) on a visual analog scale (VAS) in order of worst imaginable (0) to best possible (100) outcomes. RESULTS Women of all ages ranked VD as more desirable than CD. However, women ≥ 35 years of age had greater valuations of both MOD compared with women <35 years, with mean VAS scores of 88.4 versus 86.4 for VD (p < 0.001) and 61.5 versus 51.9 for CD (p < 0.001). Women with a college education or higher also rated both MOD as more desirable than women with less than a college education. Additionally, women who preferred VD rather than CD had greater valuations of perineal laceration (43.3 vs. 31.5, p = 0.001) and urinary incontinence (40.7 vs. 30.1, p = 0.002). CONCLUSION Significant differences exist in womens views toward MOD and peripartum outcomes, by demographics and preferred MOD. Understanding delivery preferences better enables clinicians to counsel women about labor and management options.