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We tested the hypotheses that: 1) long-term facilitation (LTF) following acute intermittent hypoxia (AIH) varies among three inbred rat strains: Fischer 344 (F344), Brown Norway (BN) and Lewis rats, and 2) ventral cervical spinal levels of genes important for phrenic LTF (pLTF) vary in association with pLTF magnitude. Lewis and F344, but not BN rats exhibited significant increases in phrenic and hypoglossal burst amplitude 60 min post-AIH that were significantly greater than control experiments without AIH, indicating strain differences in phrenic (98%, 56% and 20%, respectively) and hypoglossal LTF (66%, 77% and 5%, respectively). Ventral spinal 5-HT2A receptor mRNA and protein levels were higher in F344 and Lewis versus BN, suggesting that higher 5-HT2A receptor levels are associated with greater pLTF. More complex relationships were found for 5-HT7, BDNF and TrkB mRNA. BN had higher 5-HT7 and TrkB mRNA versus F344; BN and Lewis had higher BDNF mRNA levels versus F344. Genetic variations in serotonergic function may underlie strain differences in AIH-induced pLTF.

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The surface of the ovary has two types of epithelial cells. We have called these A and B cells and they are found in their own respective zones (A and B). To assess the scanning electron microscopic features of these cell types, 65 ovarian samples were collected from biopsies taken from 35 women with normal ovaries. Biopsies included developing follicles, corpora lutea and ovarian capsules. Type A cells were cuboidal and sometimes tall, with a mean diameter of 6.49 microns, and a mean density of microvilli of 6.48/microns 2. Type B cells, on the other hand, were flat squamous cells with broader and flat apices with mean diameters and microvillus density of 11.71 microns and 3.88/microns 2 respectively. The A and B zones were common to all surfaces including the distending follicle. Type A cells overlying the distended surface of a follicle had a mean diameter of 7.03 microns compared to a mean of 6.05 microns for the capsular surface. Type B cell diameters and the microvillus density of both types were more variable and did not differ significantly over any of the surfaces. We suggest that previous human studies which identified flattening of cells over the distending follicle were probably observing B cells. The relationship of the B zones to papillae and surface bridges on the ovarian surface, and the association of these with ovulation sites, suggests that B cells are probably metaplastic cells derived in response to chronic surface injury with ovulation.

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.

Antibody‐like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., FcRn receptor). There are limited data evaluating this transfer during organogenesis in any species. Understanding placental transfer of antibody‐like biopharmaceuticals can help to predict risk of developmental toxicity across species, including humans. To complement previously published placental transfer data in the rat with humanized IgGΔ2 (hIgG2), the timing and magnitude of transfer in the cynomolgus monkey and embryo/fetal biodistribution of maternally administered 125I‐radiolabeled hIgG2 was quantified on gestation days (GD) 35, 40, 50, 70, and 140 using gamma counting and whole body autoradiography 24 hr following intravenous injection. Chorioallantoic placental tissues were collected at all time points for Western Blot analysis with anti‐FcRn antibody. Maternally administered 125I‐hIgG2 was found in embryo/fetal tissues at all time points, including organogenesis. Embryo/fetal plasma 125I‐hIgG2 concentration increased during gestation, but only slightly up to GD 70 in embryo/fetal tissues, with hIgG2 tissue concentrations generally similar between GD70 and 140. The embryo/fetal:maternal 125I‐hIgG2 plasma concentration ratio was approximately 2.3 fold higher on GD 140, in comparison to ratios on GD 40. Importantly, placental FcRn protein expression was confirmed at all timepoints. These data demonstrate placental transfer of hIgG2 in a nonhuman primate model, and at levels comparable to the rat model, raising the potential for adverse developmental outcomes by direct antibody binding to biological targets.

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