Maternal stress during pregnancy is linked to several negative birth outcomes. The placenta, a unique pregnancy-specific organ, not only nourishes and protects the fetus but is also the major source of progesterone and estrogens. As the placenta becomes the primary source of maternal progesterone (P4) and estradiol between 6–9 weeks of gestation, and these hormones are critical for maintaining pregnancy, maternal stress may modulate levels of these steroids to impact birth outcomes. The objective was to test whether maternal perceived stress crosses the placental barrier to modulate fetal steroids, including cortisol, which is a downstream indicator of maternal hypothalamic–pituitary–adrenal (HPA) axis regulation and is associated with negative fetal outcomes. Nulliparous women, 18 years or older, with no known history of adrenal or endocrine illness were recruited during their third trimester of pregnancy at the University of California San Francisco (UCSF) Mission Bay hospital obstetrics clinics. Simultaneous measurement of 10 steroid metabolites in maternal (plasma and hair) and fetal (cord blood and placenta) samples was performed using tandem mass spectrometry along with assessment of the perceived stress score and sociodemographic status. While the maternal perceived stress score (PSS) and sociodemographic status were positively associated with each other and each with the body mass index (BMI) (r = 0.73, p = 0.0008; r = 0.48, p = 0.05; r = 0.59, p = 0.014, respectively), PSS did not correlate with maternal or fetal cortisol, cortisone levels, or fetal birth weight. Regardless of maternal PSS or BMI, fetal steroid levels remained stable and unaffected. Progesterone was the only steroid analyte quantifiable in maternal hair and correlated positively with PSS (r = 0.964, p = 0.003), whereas cord estradiol was negatively associated with PSS (r = −0.94, p = 0.017). In conclusion, hair progesterone might serve as a better marker of maternal stress than cortisol or cortisone and maternal PSS negatively impacts fetal estradiol levels. Findings have implications for improved biomarkers of stress and targets for future research to identify factors that buffer the fetus from adverse effects of maternal stress.

Endometriosis affects 2%–10% of reproductive-aged women and is one of the leading causes of chronic pelvic pain. Given the extensive diagnostic challenges, multi-system nature of the disease, and significant impacts on quality of life, there has been a long-standing recognition of the need for integrated and specialty care for women living with endometriosis. We present our experience with the development of a multidisciplinary center for endometriosis and chronic pelvic pain at the University of California San Francisco. We describe the core components of this treatment model, including (1) methods for clinical collaboration across diagnostic, medical, and surgical subspecialties; (2) promotion of surgical excision of endometriosis; (3) establishment of a patient navigator; (4) utilization of psychological interventions and integrative medicine; and (5) health care provider and community training. Since the introduction of the endometriosis center in November 2016, outpatient encounters for patients with a primary diagnosis of endometriosis increased from 2761 in 2016 to 3905 in 2018, demonstrating high demand for these services. We also highlight opportunities for collaborative research through de-identified patient surveys, clinical data, and biospecimen collection.

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Identifying biologic and genetic effects on DNA methylation (DNAm) in endometrium increases understanding of mechanisms that influence gene regulation predisposing to endometriosis and offers an opportunity for novel therapeutic target discovery. Herein, we characterize variation in endometrial DNAm and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genome-wide genotype data and methylation at 759,345 DNAm sites in endometrial samples from 984 deeply-phenotyped participants. We identify significant differences in DNAm profiles between menstrual cycle phases and at four DNAm sites between stage III/IV endometriosis and controls. We estimate that 15.4% of the variation in endometriosis is captured by DNAm, and identify DNAm networks associated with endometriosis. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independentcis-mQTL including some tissue-specific effects. We find significant differences in DNAm profiles between endometriosis sub- phenotypes and a significant association between genetic regulation of methylation in endometrium and disease risk, providing functional evidence for genomic targets contributing to endometriosis risk and pathogenesis.

Background A lack of undergraduate medical curricula on providing healthcare to transgender and gender diverse (TGD) patients has contributed to significant health disparities for TGD communities. To address this gap, we designed and evaluated a novel curriculum to train Obstetrics and Gynecology (OB/GYN) clerkship students in caring for TGD patients. Methods Following Kern’s 6-step method for curriculum development, we created a two-part curriculum on TGD healthcare topics – an online module on gender-affirming care, followed by a series of interactive cases on TGD-specific health topics. Undergraduate medical students completing their core OB/GYN clerkships at a university academic medical center (January-December 2021) were invited to complete this curriculum. Participants completed pre/post assessment surveys to assess their experience caring for TGD patients, as well as a scored knowledge assessment before and after completing the curriculum. Results Sixty-five students participated in this curricular assessment. Prior to completing the module, 45% agreed that they had received adequate TGD health training. Following module completion, students reported increased comfort in caring for transgender patients (49.2% vs. 81.5%; p < .001) and endorsed an improved fund of knowledge of both healthcare maintenance for TGD patients (61.5% vs. 100%; p < .001) and gender affirming medical therapies (60.0% vs. 96.9%; p < .001). Knowledge scores increased from a mean of 9.65 (1.81) to 12.5 (2.20) out of 15 (p < .001). In post-assessment surveys, 95% of participants agreed that the module was helpful for their learning. Qualitatively, students suggested longitudinal integration of TGD-topics into the pre-clinical curriculum, and expanded opportunities to practice patient counseling. Conclusion The findings of this study support the need for student education on TGD health. Integration of interactive, case-based TGD-care curricula into clinical training may increase medical students’ knowledge and comfort in caring for TGD patients. Ongoing efforts to integrate TGD health training into undergraduate medical student curricula are necessary.