Optimal experimental design requires synchronization of female subjects according to their hormone cycles. Female mice have a rapid four to six day estrous cycle, which consists of four distinct stages: proestrous, estrous, metestrous, and diestrous. The most documented method for staging a mouse according to the estrous cycle is characterizing the composition of their vaginal cells. We first explored the impact of a variety of approaches for obtaining vaginal cells coupled with a modified Papanicolaou stain on reliability of staging. We next tested the effectiveness of two different experimental paradigms for synchronizing mice according to their estrous cycle, comparing a combination of pregnant mare’s serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) injections versus two injections of leuprolide, a gonadotropin-releasing hormone agonist. The percentage of mice that synchronized was determined in cohorts of mice from control, PMSG /hCG and leuprolide conditions. We also determined the length of synchrony. Our results indicate that calcium alginate swabs dipped in phosphate buffered saline is the best technique for preserving vaginal cell morphology for cytological evaluation. We also observed that PMSG /hCG treated mice begin synchronization at estrus while leuprolide treated mice begin synchronization at disestrus. Both PMSG /hCG and leuprolide are equally effective for synchronizing mice according to their estrous cycle.
In response to mild stresses, some individuals develop reproductive dysfunction while others maintain normal menstrual cyclicity. Female monkeys, when exposed to mild stress, can be categorized as Highly Stress-Resilient (“HSR”; maintain normal menstrual cycles in response to stress), Medium Stress-Resilient (“MSR”; slowly become anovulatory in response to prolonged stress), or Stress-Sensitive (“SS”; rapidly become anovulatory in response to stress). We have been studying whether sensitivity to stress-induced reproductive dysfunction is associated with elevated activity of the adrenal axis in monkeys with indwelling catheters that allow undisturbed blood collection. In animals studied to date, SS (n=4) monkeys do not differ from HSR (n=6) or MSR (n=3) monkeys in cortisol secretion over a 24-hour period (F10,2=2.371, p=0.144), in response to an acute psychological stressor (F10,2=0.183, p=0.836), or in response to dexamethasone negative feedback (F10,2=0.592, p=0.571). In another sample of animals exposed to the same paradigm, we examined the expression of CRH mRNA in the PVN and the thalamus. SS monkeys express more CRH message in the caudal PVN and thalamus than HSR monkeys (n=4/group; p<0.05). We conclude that increased sensitivity to stress-induced reproductive dysfunction is not associated with elevated adrenal axis activity, but that CRH neurons in the caudal PVN and thalamus might be contributing in a non-neuroendocrine manner. Current studies are underway to examine CRH innervation to the dorsal raphe nucleus, to determine whether CRH neurons are modulating serotonergic function in this model system, as we have previously shown differences in serotonergic neural activity in SR vs. SS animals.
Background: There is a strong association between intrauterine growth restriction (IUGR) and small for gestational age (SGA) placentas. The cause is likely multifactorial, but chronic placental insufficiency may play a role. As such, we hypothesize that SGA placentas from human neonates with IUGR will show significantly more pathologic features of placental insufficiency than controls.
Design: Retrospective review of 254 consecutive singleton placentas submitted to OHSU pathology (2005-06). Clinical records were reviewed and pregnancy outcomes recorded, including: sex; weight (IUGR calculated by routine methods), trimmed weight of the placenta (SGA calculated by routine methods), gross placental infarctions, gestational age at delivery, and maternal demographics. Controls were defined as cases within the series without SGA or IUGR (e.g. submitted for meconium, infection). Histologic sections were scored by two pathologists while blinded to clinical diagnoses as positive or negative for features of placental insufficiency: accelerated villous maturation (AVM), chorangiosis, and microscopic infarctions. Significant associations were tested by X2 analysis and logistic regression for multiple variables.
Results: Similar to prior reports, we observed a strong association between IUGR and SGA placentas (X2 30.5; p <0.0001). This relationship was independent of maternal race, fetal sex, and parity, although more common in primigravidas. AVM and placental infarctions were significantly more frequent in SGA placentas with superimposed IUGR (p<0.01).
Conclusions: Our data show that pathologic features of chronic placental insufficiency are common in preterm labor, preeclampsia, and IUGR , suggesting that decreased nutritional blood flow to the fetoplacental unit may be a common cause of these pregnancy complications.
Roth et al. (2007) define a hypothesized transcriptional control network of genes expressed in the hypothalamus during the initiation of puberty, using a combination of experimental and computational evidence. In this work, I have used the information-theoretic approach of Reconstructability Analysis (RA) to explore the predicted transcription factor binding profiles used to construct the network. RA analysis predicts the presence of highly central transcription factors in the Roth et al. network in the profiles as discriminators of in-network genes relative to a housekeeping gene background set, suggesting that RA may be a good candidate for initial screenings of computationally derived transcription factor binding profiles.
This study was performed to gain a preliminary understanding of how rural Oregon clinicians and parents view the Human Papilloma Virus(HPV) vaccine and to describe how parent and clinician views and practices may be affecting the rate of uptake of the HPV vaccine in rural areas. Focus groups with parents were performed and analyzed for common themes. Also, a survey was sent to all Oregon Rural Practice-Based Research Network clincians asking questions about their recommendation and administration practices for the adolescent vaccines.
