Tanya Dailey

Environmental exposures: how to counsel preconception and prenatal patients in the clinical setting

A growing body of scientific evidence suggests that preconception and prenatal exposures can impact fetal development adversely and lead to potential long-lasting health effects. Reproductive health professionals have little training on these exposures and how to counsel patients effectively. We present short summaries of some of the most common environmental exposures and give providers practical tools with which to counsel patients in the clinical setting. These tools may enable practitioners to help prevent harmful environmental exposures and to reduce the risk of future adverse health impacts for the prenatal and preconception patient population.

Prostaglandin E2-regulated cervical ripening: analysis of proteoglycan expression in the rat cervix.

OBJECTIVE Prostaglandins reduce cervical resistance by reorganizing collagen fibrils. Proteoglycans are involved in collagen fibril organization and structure. We evaluated the changes in proteoglycan composition induced by prostaglandin E(2) (PGE(2)). STUDY DESIGN Prostaglandins were administered intravaginally to induce cervical ripening in timed pregnant Sprague-Dawley rats. Changes in proteoglycan messenger ribonucleic acid (mRNA) expression were measured using reverse transcription (RT-PCR) for core protein. Fluorophore assisted carbohydrate gel electrophoresis (FACE) was used to evaluate proteoglycan glycosaminoglycan composition along with size exclusion high-performance liquid chromatography (HPLC). RESULTS No change in core protein mRNA expression was detected after PGE(2) treatment. Total glycosaminoglycan (GAG) decreased more than 20% after PGE(2) (P = .02). FACE demonstrated a shift in disaccharide subunit composition after PGE(2), with a decrease in 4-sulfated disaccharides (P = .02). HPLC confirmed a decrease in total GAG (P = .04). CONCLUSION Although there was no change in core protein mRNA expression, alterations in GAG composition was detected after PGE(2). The decrease in sulfated GAG could decrease electrostatic interactions that would weaken interfibrillar interactions. These findings would be consistent with a decline in cervical resistance.

Androgen-regulated cervical ripening: a structural, biomechanical, and molecular analysis

OBJECTIVE Androgens regulate biomechanical responses in load-bearing tissues. Evidence suggests that androgens may play a role in the cervix. We hypothesized that androgens directly regulate cervical remodeling by altering both collagen structure and proteoglycan composition. STUDY DESIGN Cervical resistance was evaluated using the cervical creep method after the administration of intravaginal dihydrotestosterone or oral flutamide. Microstructural changes in collagen were evaluated by transmission electron microscopy and polarized light birefringence. Proteoglycan expression was evaluated by reverse transcription-polymerase chain reaction for the core proteins (decorin, biglycan, fibromodulin, aggrecan, versican) and fluorophore-assisted carbohydrate analysis. RESULTS Dihydrotestosterone decreased cervical resistance, whereas flutamide inhibited the decline in cervical resistance, compared with vehicle controls. Flutamide was associated with higher levels of organized collagen and increased aggrecan expression with a greater proportion of chondroitin/dermatan sulfate glycosaminoglycans. Flutamide inhibited the increase in hyaluronan. CONCLUSION Androgens appear to play a role in regulating cervical resistance by altering proteoglycan content. Structural analysis indicates that flutamide may alter collagen fibril organization and/or structure.

The contribution of maternal race/ethnicity and fetal sex to prematurity in twins.

OBJECTIVE The contribution of male fetal sex to twin preterm birth (PTB) rates was evaluated in the United States. STUDY DESIGN The 2002 National Center for Health Statistics Natality database was analyzed for fetal sex and twin gestations based on birth sex for MM and FF pairs (M, male; F, female). Multivariable Cox proportional hazards regression was applied to estimate the hazard ratio for PTB with adjustments for known risks. RESULTS Thirty-three thousand nine hundred twenty-six pairs were analyzed. PTBs between 20-36 completed weeks occurred in 59.1% MM pairs and 57.5% FF pairs. MM sex was an independent risk factor for PTB. This effect was greatest for deliveries between 20-29 weeks (hazard ratio, 1.224; 95% CI, 1.113-1.346). The effect was most pronounced in non-Hispanic white MM pairs. CONCLUSION In the United States, MM pairs are at greater risk for PTB. Race and ethnicity modulate sex effects. Further studies are needed to understand potential mechanisms.

THE ROLE OF TRANSFORMING GROWTH FACTOR β IN CERVICAL REMODELING WITHIN THE RAT CERVIX

OBJECTIVE Transforming growth factor beta (TGFbeta) plays a central role in extracellular matrix remodeling. We hypothesized that TGFbeta signaling is involved in cervical remodeling. This study evaluated patterns within this signaling pathway. STUDY DESIGN The cervices of nonpregnant and timed pregnant rats were obtained. Messenger ribonucleic acid (mRNA) expression of TGFbeta1, TGFbeta receptor 1 (TbetaR1), TbetaR2, and TbetaR3 was evaluated. Four animals were euthanized for each time point. Western blotting was performed for protein expression. Phosphorylated mothers against decapentaplegic (Smad)-2 and -3 phosphorylation was assessed to evaluate TGFbeta activation. RESULTS TGFbeta1 mRNA increased through day 21 and declined on day 22 (analysis of variance, P = .001). TbetaR1 expression was unchanged. TbetaR2 and TbetaR3 mRNA expression was similar to TGFbeta1. TbetaR3 protein expression was similar to mRNA. Smad2 phosphorylation paralleled changes in TbetaR3. CONCLUSION Components of the TGFbeta signaling pathway increase during pregnancy along with Smad2 activation. The decline on day 22 correlates with a transition to the ripening phase supporting a role in cervical remodeling.

Lupus Nephritis Mimicking Pyelonephritis in Pregnancy

Background: Systemic lupus erythematosis (SLE) is a multisystemic autoimmune connective tissue disorder that presents with a wide range of clinical manifestations including renal involvement. Routine prenatal care includes assessment of renal function. Case: A 29-year-old nullipara presented at 17 weeks with fever, vomiting, and costovertebral angle tenderness 1 week after being treated for a presumed urinary tract infection. On presentation, new-onset hypertension was noted. Inpatient evaluation established a diagnosis of SLE with lupus nephritis. The pregnancy ended with intrauterine fetal demise. Conclusion: SLE is a disease with complex and protean clinical manifestations. It should appear on the differential when more common disease processes are ruled out. Routine prenatal care can detect otherwise silent and undiagnosed renal disease, and with early intervention improve prognosis.