Increasing adiposity in normal ovulatory women affects adipocytokine expression in subcutaneous and visceral abdominal fat.

OBJECTIVE: To determine which adipocytokines are differentially expressed as a function of body mass index (BMI), to compare expression of adipocytokines in abdominal subcutaneous and omental fat, and to correlate these findings with serum levels, BMI, and parameters of insulin resistance. METHODS: Serum and subcutaneous (sc) and omental (om) tissue were obtained from lean and obese ovulatory women undergoing gynecologic surgery. We determined adipocytokine expression in sc versus om abdominal fat and related this to increasing BMI. RESULTS: Serum leptin was higher and adiponectin lower in overweight subjects. Adipocytokines had higher expression in sc abdominal versus om adipose tissue with the most significant difference observed for leptin (P=0.01). As BMI increased, sc leptin expression increased and adiponectin expression decreased. The leptin/adiponectin ratio correlated significantly with BMI (R=0.84, P=0.0001). CONCLUSION: Increased adipocytokine expression correlates with BMI. Abdominal sc tissue has greater adipocytokine expression overall. The serum leptin/adiponectin ratio is highly correlated with BMI. These data may help in our understanding of how obesity affects women in a variety of ways.

Hysterosalpingography with selective salpingography.

OBJECTIVE: To evaluate the use of selective salpingography to achieve tubal patency in patients with proximal fallopian tube occlusion on hysterosalpingography (HSG). STUDY DESIGN: We performed a retrospective cohort study on 116 infertile women (age 37.7 +/- 4.6 years) with proximal tubal obstruction treated with selective salpingography. Success was defined as opening at least 1 fallopian tube. Pregnancy was defined as having a positive beta-hCG level. RESULTS: A total of 151 tubes were blocked on HSG before tubal catheterization; 103 tubes were opened by selective salpingography. Of 116 patients, 84 (72.4%) had successful procedures with at least 1 tube opened by catheterization. Of the 116, 32 (27.6%) had failed procedures with no tubes opened. Of 83 patients, 30 (36.1%) with successful procedures achieved pregnancy. Of these pregnancies, 16 occurred spontaneously or following ovulation induction and 5 pregnancies occurred in the failure group, allfollowing in vitro fertilization. CONCLUSION: Selective salpingography is useful in demonstrating tubal patency, reducing the diagnosis of tubal disease and potentially minimizing surgery in infertile patients.

Transepithelial glucose transport and metabolism in BeWo choriocarcinoma cells.

Glucose transporters in the placental, epithelial syncytiotrophoblast barrier are asymmetrically arranged (microvillous>basal), leading to the hypothesis of a rate-limiting role for the basal membrane in transepithelial transport. This is significant since the changes which have been observed in basal membrane glucose transporter expression over gestation and in conditions such as diabetes would generate changes in maternal-to-foetal glucose transport. This study was designed to test whether the basal membrane of the syncytiotrophoblast is the rate-limiting step in transepithelial transport and to investigate the effects of metabolism on transpithelial transport. In the absence of a transporting syncytiotrophoblast monolayer, the BeWo choriocarcinoma cell line, derived from trophoblast and plated on a permeable support, was used as a model since it has an asymmetric distribution of glucose transporter activity, similar to the syncytiotrophoblast. Inhibition of basal membrane glucose transport with p -chloromercuribenzene-sulfonate (p CMBS) produced a proportional change in transepithelial transport, whereas this latter parameter was relatively insensitive to inhibition of microvillous membrane glucose transporters. These data demonstrate that the basal membrane is the rate-limiting step in transepithelial glucose transport. Experiments involving stimulation and inhibition of cellular glucose consumption demonstrated that there is a single intracellular glucose pool in BeWo cells, supplying both metabolism and transcellular transport.

A unique human chorionic gonadotropin antagonist suppresses ovarian hyperstimulation syndrome in rats.

Ovarian hyperstimulation syndrome (OHSS) is a complication of in vitro fertilization associated with physiological changes after hCG administration to induce final oocyte maturation. It presents as widespread increases in vascular permeability and, in rare cases, results in cycle cancellation, multi-organ dysfunction, and pregnancy termination. These physiological changes are due primarily to activation of the vascular endothelial growth factor (VEGF) system in response to exogenous human chorionic gonadotropin (hCG). An hCG antagonist (hCG-Ant) could attenuate these effects by competitively binding to the LH/CG receptor, thereby blocking LH activity in vivo. We expressed a form of hCG that lacks three of its four N-linked glycosylation sites and tested its efficacy as an antagonist. The hCG-Ant binds the LH receptor with an affinity similar to native hCG and inhibits cAMP response in vitro. In a rat model for ovarian stimulation, hCG-Ant dramatically reduces ovulation and steroid hormone production. In a well-established rat OHSS model, vascular permeability and vascular endothelial growth factor (VEGF) expression are dramatically reduced after hCG-Ant treatment. Finally, hCG-Ant does not appear to alter blastocyst development when given after hCG in mice. These studies demonstrate that removing specific glycosylation sites on native hCG can produce an hCG-Ant that is capable of binding without activating the LH receptor and blocking the actions of hCG. Thus hCG-Ant will be investigated as a potential therapy for OHSS.

Biomarkers of ovarian function in girls and women with classic galactosemia.

OBJECTIVE: To determine whether premature ovarian insufficiency (POI) associated with classic galactosemia results from a true impairment of ovarian function or from aberrant FSH. DESIGN: Cross-sectional study. SETTING: University research laboratory. PATIENT(S): Study subjects included 35 girls and women with galactosemia and 43 control girls and women between the ages of <1 and 51 years. INTERVENTION(S): Blood sampling and medical and reproductive histories were obtained. MAIN OUTCOME MEASUREMENT(S): We determined FSH and anti-Müllerian hormone (AMH) levels in subjects with and without classic galactosemia. FSH bioactivity was measured in a subset of girls and women with and without galactosemia who were not on hormone therapy. RESULT(S): FSH levels were significantly higher and AMH levels were significantly lower in our galactosemic cases relative to controls. FSH bioactivity did not significantly differ between cases and controls. CONCLUSION(S): Close to 90% of girls and women with classic galactosemia have a profound absence of ovarian function, a deficit that is evident shortly after birth, if not before. These patients have no evidence of abnormally functioning FSH. AMH levels can be assessed before menarche or after initiation of hormone therapy and may supplement FSH as a useful blood biomarker of ovarian function for patients with classic galactosemia.