The Embodiment of Insult: A Theory of Biobehavioral Response to Workplace Incivility.

This article builds a broad theory to explain how people respond, both biologically and behaviorally, when targeted with incivility in organizations. Central to our theorizing is a multifaceted framework that yields four quadrants of target response: reciprocation, retreat, relationship repair, and recruitment of support. We advance the novel argument that these behaviors not only stem from biological change within the body but also stimulate such change. Behavioral responses that revolve around affiliation and produce positive social connections are most likely to bring biological benefits. However, social and cultural features of an organization can stand in the way of affiliation, especially for employees holding marginalized identities. When incivility persists over time and employees lack access to the resources needed to recover, we theorize, downstream consequences can include harms to their physical health. Like other aspects of organizational life, this biobehavioral theory of incivility response is anything but simple. But it may help explain how seemingly "small" insults can sometimes have large effects, ultimately undermining workforce well-being. It may also suggest novel sites for incivility intervention, focusing on the relational and inclusive side of work. The overarching goal of this article is to motivate new science on workplace incivility, new knowledge, and ultimately, new solutions.

Bone density and frame size in adult women: Effects of body size, habitual use, and life history.

OBJECTIVE: Bone mineral density (BMD) and frame size are important predictors of future bone health, with smaller frame size and lower BMD associated with higher risk of later fragility fractures. We test the effects of body size, habitual use, and life history on frame size and cortical BMD of the radius and tibia in sample of healthy adult premenopausal women. METHODS: We used anthropometry and life history data from 123 women (age 18-46) from rural Poland. Standard techniques were used to measure height, weight, and body fat. Life history factors were recorded using surveys. Grip strength was measured as a proxy for habitual activity, wrist breadth for skeletal frame size. Cortical BMD was measured at the one-third distal point of the radius and mid-point of the tibia using quantitative ultrasound (reported as speed of sound, SoS). RESULTS: Radial SoS was high (mean t-score 3.2 ± 1.6), but tibia SoS was average (mean t-score 0.35 ± 1.17). SoS was not associated with age, although wrist breadth was positively associated with age after adjusting for height. Radius SoS was not associated with measures of body size, habitual use, or life history factors. Wrist breadth was associated with body size (p < .05 for all), lean mass, and grip strength. Tibia SoS was associated with height. Life history factors were not associated with frame size or cortical SoS. CONCLUSIONS: Habitual use and overall body size are more strongly associated with frame size and cortical SoS than life history factors in this sample of healthy adult women.

What are friends for? The impact of friendship on communicative efficiency and cortisol response during collaborative problem solving among younger and older women.

Conversation is a skilled activity that depends on cognitive and social processes, both of which develop through adulthood. We examined the effects of age and partner familiarity on communicative efficiency and cortisol reactivity. Younger and older women interacted with familiar or unfamiliar partners in a dyadic collaborative conversation task (N = 8 in each group). Regardless of age, referential expressions among familiar and unfamiliar partners became more efficient over time, and cortisol concentrations were lower for speakers interacting with familiar partners. These findings suggest that communicative effectiveness is largely preserved with age, as is the stress-buffering effect of a familiar partner.

Declining ages at menarche in an agrarian rural region of Poland.

OBJECTIVE: Age at menarche in Poland has varied with political and socioeconomic changes. An increase in age at menarche corresponded to a period of economic crisis and food rationing between 1976 and 1989. Experiencing food shortages in utero or during childhood development can affect menarcheal timing, but this national effect may be buffered in local agrarian regions growing their own food. Here we examine patterns of age at menarche over time in the rural, agrarian Beskid Wyspowy region of southern Poland. METHODS: This study examined menarcheal timing using data collected from Polish women (n = 1326) recruited at the Mogielica Human Ecology Study Site between 2003 and 2018. Simple linear regressions were used to assess changing ages at menarche over time. Comparisons between ages at menarche for women born before and after the fall of communism in 1989 were assessed via one-way analysis of variance. RESULTS: Age at menarche has declined over time in the Beskid Wyspowy region of southern Poland from 1920 to 2000 (R2 = .08, P < .0001). There was not a statistically significant increase or decrease in age at menarche for women born and growing up during the period of food rationing. CONCLUSIONS: The declining age at menarche is likely reflective of a transitioning environment, suggesting that major socioeconomic changes affect life history traits like pubertal timing. Living in agricultural regions may have helped buffer the increasing ages at menarche seen in other areas of Poland during times of food rationing.

From maternal tending to adolescent befriending: The adolescent transition of social support.

Attachment theory holds that parental relationships have lifelong effects on offspring social lives. The tend-and-befriend hypothesis posits that female friendships among humans evolved as part of a primate-wide coping mechanism to mediate stress by relying on social support. Here we bridge developmental and evolutionary frameworks to examine adolescent girls' perception of their reliance on female friendship for social support, how perceptions of parental relationships affect peer relationships, and the extent to which parent and peer relationships buffer depressive symptoms. We predict perceived maternal relationship quality will be positively associated with close female friendships, and maternal relationships, paternal relationships, and female friendship will buffer depressive symptoms. Participants were adolescent girls from a summer science camp (N = 95). Participants filled out demographic information, social network surveys, the Parent-Adolescent Communication Scale, and the Center for Epidemiology Depression Scale. Data was analyzed with Pearson's correlations, t tests, and path analysis. Adolescent girls with few female friends, compared with girls who had more than two very close female friends, experienced more depressive symptoms (t = 3.382, p = .001, D = 0.784). Adolescent girls with few female friends experienced more depressive symptoms compared to girls with two or more very close female friends (t = 3.382, p = .001, D = 0.784). Stronger maternal and paternal relationships were associated with having more female friends (maternal: t = -3.213, p = .003, D = 0.837; paternal: t = -2.432; p = .017). In the path analysis model, only maternal relationship quality significantly predicted female friendship category (ß = .33, CR = 2.770, p < .006). Furthermore, participants with two or more very close female friends and higher paternal relationship quality had significantly fewer depressive symptoms (friends; ß = -.19, CR = -2.112, p = .035; paternal: ß = -.33, CR = -3.220, p < .001), and older participants had more depressive symptoms (ß = .17, CR = -1.931, p = .036). These results provide additional support for the tend-and-befriend hypothesis, suggesting that maternal tending sets the stage for close female friendships.

Physical activity in women of reproductive age in a transitioning rural Polish population.

OBJECTIVE: Health research often focuses on moderate and vigorous intensity physical activity while neglecting low-intensity habitual activities. Our aim was to understand habitual physical activity in women from a transitioning economy using a physical activity monitor. METHODS: This study investigated physical activity in 68 healthy premenopausal women (age 18-46) in rural Poland using FitBit One activity trackers for 1 week. Standard anthropometric techniques were used to measure height, weight, and body fat. Daily physical activity data were analyzed for step counts as well as duration and intensity. RESULTS: This sample of rural Polish women traveled a mean of 8428 (SD = 2650) steps per day. Time spent lightly active, fairly active, and very active were measured as 337.1 (SD = 87.8), 19.6 (SD = 30.5), and 6.7 (SD = 8.6) minutes per day, respectively. Total time active and time spent lightly active were associated with daily steps (P < 0.001 for both), and time lightly active increased with age (P = 0.02). No other significant relationships were observed between physical activity measures and BMI, age, or body fat. CONCLUSIONS: In this sample, women spend a significant amount of time engaged in light-intensity physical activity and travel a relatively high number of steps per day. Our data suggest that in this population, total daily activity does not depend on age in women between 18 and 46. We suggest that measurement methods which include low-intensity activity may better characterize habitual physical activity in women who are expected to be performing large amounts of domestic labor.

Cycle-phase dependent associations between CRP, leptin, and reproductive hormones in an urban, Canadian sample.

OBJECTIVES: To assess the relationships among reproductive hormones, follicular development, inflammation, and adiposity in a sample of urban, Canadian women. MATERIALS AND METHODS: Participants (n = 41) had blood collected every 3 days through one interovulatory interval (IOI) to measure estradiol, progesterone, LH, FSH, leptin, and C-reactive protein (CRP). Participants underwent daily transvaginal ultrasound examinations during the IOI to quantify all follicles > 2 mm. CRP and leptin tertiles were used to compare conditions of high and low inflammatory processes and adiposity, respectively. RESULTS: Luteal phase estradiol, luteal phase LH, and follicular phase progesterone were lower among individuals in the highest CRP tertile (adjusted r(2) = 0.63, 0.70, 0.76, respectively). Luteal and follicular phase follicle diameter was greatest in the high CRP tertile (adjusted r(2) = 0.68, 0.71). Follicular phase progesterone was lowest among individuals in the highest leptin tertile, and follicular phase FSH was lowest among individuals in the lowest leptin tertile (adjusted r(2) = 0.54, 0.45). Luteal phase follicle diameter was highest among those in the moderate leptin tertile (adjusted r(2) = 0.49). DISCUSSION: This study is a first comprehensive assessment of the relationship between multiple ovarian function components and inflammatory biomarkers. The results are interpreted to mean that inflammatory and energetic stressors produce differential effects depending on population, adiposity, and cycle phase. Am J Phys Anthropol 160:389-396, 2016. © 2016 Wiley Periodicals, Inc.

The induction of pro-angiogenic processes within a collagen scaffold via exogenous estradiol and endometrial epithelial cells.

Nutrient transport remains a major limitation in the design of biomaterials. One approach to overcome this constraint is to incorporate features to induce angiogenesis-mediated microvasculature formation. Angiogenesis requires a temporal presentation of both pro- and anti-angiogenic factors to achieve stable vasculature, leading to increasingly complex biomaterial design scheme. The endometrium, the lining of the uterus and site of embryo implantation, exemplifies a non-pathological model of rapid growth, shedding, and re-growth of dense vascular networks regulated by the dynamic actions of estradiol and progesterone. In this study, we examined the individual and combined response of endometrial epithelial cells and human umbilical vein endothelial cells to exogenous estradiol within a three-dimensional collagen scaffold. While endothelial cells did not respond to exogenous estradiol, estradiol directly stimulated endometrial epithelial cell transduction pathways and resulted in dose-dependent increases in endogenous VEGF production. Co-culture experiments using conditioned media demonstrated estradiol stimulation of endometrial epithelial cells can induce functional changes in endothelial cells within the collagen biomaterial. We also report the effect of direct endometrial epithelial and endothelial co-culture as well as covalent immobilization of estradiol within the collagen biomaterial. These efforts establish the suitability of an endometrial-inspired model for promoting pro-angiogenic events within regenerative medicine applications. These results also suggest the potential for developing biomaterial-based models of the endometrium.

Women who deliver twins are more likely to smoke and have high frequencies of specific SNPs: Results from a sample of African-American women who delivered preterm, low birth weight babies.

OBJECTIVES: We examine if there are genetic and environmental differences between mothers of singleton and multiple pregnancies in a sample of African-American mothers. METHODS: We focus on genomic areas suggested to increase or decrease the odds of multiple pregnancies. We computed the odds ratio (OR) and the 95% confidence interval (CI) for each SNP unadjusted or adjusted with smoking. SNPs' allelic differences between mothers of multiple pregnancies and singletons were also tested using Fisher's exact test. We considered additive terms for the SNPs' genotypes, smoking, and a multiplicative interaction term of two selected SNPs' genotypes. RESULTS: We found significant interactions between smoking and SNPs of the CYP19A, MDM4, MTHFR and TP53 genes which correlated with higher odds of twinning. We also found a significant interaction between SNPs at the TP53 (rs8079544) and MTHFR gene (rs4846049), where the interaction between the homozygotes (TT for rs8079544, GG for rs4846049) correlated with lowered odds of multiple pregnancy. CONCLUSIONS: We provide a mechanistic explanation and preliminary evidence for previous reports that mothers of twins are more likely to have smoked, despite seemingly conflicting evidence for the fertility-reducing effects of nicotine. Nicotine, as an aromatase inhibitor, inhibits estrogen synthesis and may allow for greater production of gonadotropins. While smoking may have deleterious effects on fertility across many genotypes, in women of specific genotypes it may raise their odds of producing twins. TP53 involvement suggests the necessity of future work examining relationships between women who bear multiples and cancer risk.

Endometrial decidualization status modulates endometrial microvascular complexity and trophoblast outgrowth in gelatin methacryloyl hydrogels.

The endometrium undergoes rapid cycles of vascular growth, remodeling, and breakdown during the menstrual cycle and pregnancy. Decidualization is an endometrial differentiation process driven by steroidal sex hormones that is critical for blastocyst-uterine interfacing and blastocyst implantation. Certain pregnancy disorders may be linked to decidualization processes. However, much remains unknown regarding the role of decidualization and reciprocal trophoblast-endometrial interactions on endometrial angiogenesis and trophoblast invasion. Here, we report an engineered endometrial microvascular network embedded in gelatin hydrogels that displays morphological and functional patterns of decidualization. Vessel complexity and biomolecule secretion are sensitive to decidualization and affect trophoblast motility, but that signaling between endometrial and trophoblast cells was not bi-directional. Although endometrial microvascular network decidualization status influences trophoblast cells, trophoblast cells did not induce structural changes in the endometrial microvascular networks. These findings add to a growing literature that the endometrium has biological agency at the uterine-trophoblast interface during implantation. Finally, we form a stratified endometrial tri-culture model, combining engineered microvascular networks with epithelial cells. These endometrial microvascular networks provide a well-characterized platform to investigate dynamic changes in angiogenesis in response to pathological and physiological endometrial states.

Relationships between biomarkers of inflammation, ovarian steroids, and age at menarche in a rural Polish sample.

OBJECTIVES: To test the hypothesis that life history trade-offs between maintenance and reproductive effort would be evident through inverse associations between levels of a biomarker of inflammation [C-reactive protein (CRP)], and ovarian hormones. Associations between CRP and age at menarche were also explored. METHODS: Urinary CRP, salivary progesterone, and estradiol were measured over one menstrual cycle from rural Polish women (n = 25), representing a natural fertility sample. Age of menarche was assessed through interview recall methods. We used minimum second-order Akaike Information Criteria as a means of multiple regression model selection, and repeated measures ANOVA to test cycle-dependent hypotheses. RESULTS: Comparisons of individuals in high and low CRP tertiles revealed that those with high CRP had significantly lower progesterone (luteal P = 0.03, mid luteal P = 0.007) but not estradiol (follicular P = 0.21, luteal P = 0.15) concentrations through the menstrual cycle. However, when the age at menarche was included in the analysis, both age at menarche and urinary CRP were negatively associated with estradiol (R(2) = 0.44, P = 0.0007). Age at menarche and estradiol were the strongest negative predictors of CRP (R(2) = 0.52, P = 0.0001). CONCLUSIONS: Inflammation itself may suppress ovarian function, or indicate immune challenges that lead to ovarian suppression. The timing of menarche may also influence adult inflammatory sensitivity and ovarian hormone concentrations. This lends support to existing models of trade-offs between maintenance and reproduction in women.

Role of Extracellular Matrix Biomolecules on Endometrial Epithelial Cell Attachment and Cytokeratin 18 Expression on Gelatin Hydrogels.

The endometrium undergoes profound changes in tissue architecture and composition, both during the menstrual cycle as well as in the context of pregnancy. Dynamic remodeling processes of the endometrial extracellular matrix (ECM) are a major element of endometrial homeostasis, including changes across the menstrual cycle. A critical element of this tissue microenvironment is the endometrial basement membrane, a specialized layer of proteins that separates the endometrial epithelium from the underlying endometrial ECM. Bioengineering models of the endometrial microenvironment that present an appropriate endometrial ECM and basement membrane may provide an improved environment to study endometrial epithelial cell (EEC) function. Here, we exploit a tiered approach using two-dimensional high-throughput microarrays and three-dimensional gelatin hydrogels to define patterns of EEC attachment and cytokeratin 18 (CK18) expression in response to combinations of endometrial basement membrane proteins. We identify combinations (collagen IV + tenascin C; collagen I + collagen III; hyaluronic acid + tenascin C; collagen V; collagen V + hyaluronic acid; collagen III; and collagen I) that facilitate increased EEC attachment, increased CK18 intensity, or both. We also identify significant EEC mediated remodeling of the methacrylamide-functionalized gelatin matrix environment via analysis of nascent protein deposition. Together, we report efforts to tailor the localization of basement membrane-associated proteins and proteoglycans in order to investigate tissue-engineered models of the endometrial microenvironment.

Dietary Protein Source Matters for Changes in Inflammation Measured by Urinary C-Reactive Protein in Rural Polish Women.

Objectives: Multiple macronutrients have been shown to affect systemic inflammation, a well-known predictor of chronic disease. Less often, varying sources of these macronutrients are examined. Different subsistence environments lead to varying access to protein sources which, combined with physical activity patterns, may lead to different relationships than among more typically studied sedentary, industrialized populations. This study hypothesizes an association between dietary protein intake and urinary C-Reactive Protein (CRP) concentration in women from a rural, agrarian Polish community. Materials and Methods: We assessed protein intake and their sources for 80 nonsmoking, premenopausal Polish women who were not pregnant, nursing, or on hormonal birth control during the study or within the previous six months. Each participant completed multiple 24-hour dietary recalls during one menstrual cycle. Participants collected morning void urinary samples daily over one menstrual cycle for urinary CRP analysis. We analyzed relationships between plant and animal protein intake and CRP over the menstrual cycle by multiple linear regression. Results: Plant protein in cereal foods was significantly positively associated with cycle-average urinary CRP concentrations (p<0.05) after controlling for body fat percent, total energy intake, and dietary fiber. Foods containing animal protein were not significantly associated with CRP. Discussion: Contents of this population's main plant and animal protein sources differ from those of more commonly studied industrialized populations. Within the context of a population's typical diet, more emphasis may need to be placed on particular source of protein consumed, beyond plant versus animal, in order to understand relationships with CRP.

Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination.

Early in 2021, many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. We investigated this emerging phenomenon of changed menstrual bleeding patterns among a convenience sample of currently and formerly menstruating people using a web-based survey. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual, while 44% reported no change after being vaccinated. Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of postmenopausal people reported breakthrough bleeding. We found that increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever and/or fatigue), history of pregnancy or birth, and ethnicity. Generally, changes to menstrual bleeding are not uncommon or dangerous, yet attention to these experiences is necessary to build trust in medicine.

Tuning Trophoblast Motility in a Gelatin Hydrogel via Soluble Cues from the Maternal-Fetal Interface.

Trophoblast cells play multiple critical roles in pregnancy, notably modulating blastocyst attachment to the endometrium as well as invading into and actively remodeling the endometrium to facilitate biotransport needs of the growing embryo. Despite the importance of trophoblast invasion for processes essential at early stages of pregnancy, much remains unknown regarding the balance of signaling molecules that may influence trophoblast invasion into the endometrium. The goal of this study was to use three-dimensional trophoblast spheroid motility assays to examine the effect of cues from the maternal-fetal interface on trophoblast motility. We report use of a methacrylamide-functionalized gelatin hydrogel to support quantitative analysis of trophoblast outgrowth area and cell viability. We show that this multidimensional model of trophoblast motility can resolve quantifiable differences in outgrowth area and viability in the presence of a known invasion promoter, epidermal growth factor, and a known invasion inhibitor, transforming growth factor ß1. We then investigate the sensitivity of trophoblast motility to cortisol, a hormone associated with exogenous stressors. Together, this approach provides a toolset to investigate the coordinated action of physiological and pathophysiological processes on early stages of trophoblast invasion.

Tuning trophoblast motility in a gelatin hydrogel via soluble cues from the maternal-fetal interface.

Trophoblast cells play multiple critical roles in pregnancy, notably modulating blastocyst attachment to the endometrium as well as invading into and actively remodeling the endometrium to facilitate biotransport needs of the growing embryo. Despite the importance of trophoblast invasion for processes essential at early stages of pregnancy, much remains unknown regarding the balance of signaling molecules that may influence trophoblast invasion into the endometrium. The goal of this study was to use three-dimensional trophoblast spheroid motility assays to examine the effect of cues from the maternal-fetal interface on trophoblast motility. We report use of a methacrylamide-functionalized gelatin (GelMA) hydrogel to support quantitative analysis of trophoblast outgrowth area and cell viability. We show this multidimensional model of trophoblast motility can resolve quantifiable differences in outgrowth area and viability in the presence of a known invasion promoter, epidermal growth factor, and a known invasion inhibitor, transforming growth factor ß1. We then investigate the sensitivity of trophoblast motility to cortisol, a hormone associated with exogenous stressors. Together, this approach provides a toolset to investigate the coordinated action of physiological and pathophysiological processes on early stages of trophoblast invasion.

Reproductive ecology and the endometrium: physiology, variation, and new directions.

Endometrial function is often overlooked in the study of fertility in reproductive ecology, but it is crucial to implantation and the support of a successful pregnancy. Human female reproductive physiology can handle substantial energy demands that include the production of fecund cycles, ovulation, fertilization, placentation, a 9-month gestation, and often several years of lactation. The particular morphology of the human endometrium as well as our relative copiousness of menstruation and large neonatal size suggests that endometrial function has more resources allocated to it than many other primates. The human endometrium has a particularly invasive kind of hemochorial placentation and trophoblast that maximizes surface area and maternal-fetal contact, yet these processes are actually less efficient than the placentation of some of our primate relatives. The human endometrium and its associated processes appear to prioritize maximizing the transmission of oxygen and glucose to the fetus over efficiency and protection of maternal resources. Ovarian function controls many aspects of endometrial function and thus variation in the endometrium is often a reflection of ecological factors that impact the ovaries. However, preliminary evidence and literature from populations of different reproductive states, ages and pathologies also suggests that ecological stress plays a role in endometrial variation, different from or even independent of ovarian function. Immune stress and psychosocial stress appear to play some role in the endometrium's ability to carry a fetus through the mechanism of inflammation. Thus, within reproductive ecology we should move towards a model of women's fecundity and fertility that includes many components of ecological stress and their effects not only on the ovaries, but on processes related to endometrial function. Greater attention on the endometrium may aid in unraveling several issues in hominoid and specifically human evolutionary biology: a low implantation rate, high rates of early pregnancy loss, prenatal investment in singletons but postnatal support of several dependent offspring at once, and higher rate of reproductive and pregnancy-related pathology compared to other primates, ranging from endometriosis to preeclampsia. The study of the endometrium may also complicate some of these issues, as it raises the question of why humans have a maximally invasive placentation method and yet slow fetal growth rates. In this review, I will describe endometrial physiology, methods of measurement, variation, and some of the ecological variables that likely produce variation and pregnancy losses to demonstrate the necessity of further study. I propose several basic avenues of study that leave room for testable hypotheses in the field of reproductive ecology. And finally, I describe the potential of this work not just in reproductive ecology, but in the resolution of broader women's health issues.

A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion.

The endometrium is the lining of the uterus and site of blastocyst implantation. Each menstrual cycle, the endometrium cycles through rapid phases of growth, remodelling and breakdown. Significant vascular remodelling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodelling enhance blood flow to the embryo ahead of placentation. Understanding the mechanisms of endometrial vascular remodelling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective of this study was to develop a tissue engineering platform to investigate the processes of endometrial angiogenesis and trophoblast invasion in a three-dimensional environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue, supports the formation of endometrial endothelial cell networks with human umbilical vein endothelial cells and human endometrial stromal cells as an artificial endometrial perivascular niche and the culture of an endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.

Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels.

Biomaterial vascularization remains a major focus in the field of tissue engineering. Biomaterial culture of endometrial cells is described as a platform to inform the design of proangiogenic biomaterials. The endometrium undergoes rapid growth and shedding of dense vascular networks during each menstrual cycle mediated via estradiol and progesterone in vivo. Cocultures of endometrial epithelial and stromal cells encapsulated within a methacrylamide-functionalized gelatin hydrogel are employed. It is reported that proangiogenic gene expression profiles and vascular endothelial growth factor production are hormone dependent in endometrial epithelial cells, but that hormone signals have no effect on human telomerase reverse transcriptase (hTERT)-immortalized endometrial stromal cells. This study subsequently examines whether the magnitude of epithelial cell response is sufficient to induce changes in human umbilical vein endothelial cell network formation. Incorporation of endometrial stromal cells improves vessel formation, but co-culture with endometrial epithelial cells leads to a decrease in vascular formation, suggesting the need for stratified cocultures of endometrial epithelial and stromal cells with endothelial cells. Given the transience of hormonal signals within 3D biomaterials, the inclusion of sex hormone binding globulin (SHBG) to alter the bioavailability of estradiol within the hydrogel is reported, demonstrating a strategy to reduce diffusive losses via SHBG-mediated estradiol sequestration.