Placental transfer of Fc-containing biopharmaceuticals across species, an industry survey analysis.

Background: Understanding species differences in placental transfer of Fc-containing biopharmaceuticals (particularly monoclonal antibodies) will improve human risk extrapolation from nonclinical embryo-fetal development toxicity data.

Methods: Maternal and fetal concentration data from 10, 15, 8, and 34 Fc-containing biopharmaceuticals in the rabbit, rat, mouse, and cynomolgus monkey, respectively, from an industry survey were analyzed for trends in placental transfer.

Results And Conclusions: Embryonic (before the end of organogenesis) exposure was assessed in one molecule each in rabbit, rat, and mouse, but detectable levels were present only in rodents.

Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay - progress report on phase I.

This report provides a progress update of a consortium effort to develop a harmonized zebrafish developmental toxicity assay. Twenty non-proprietary compounds (10 animal teratogens and 10 animal non-teratogens) were evaluated blinded in 4 laboratories. Zebrafish embryos from pond-derived and cultivated strain wild types were exposed to the test compounds for 5 days and subsequently evaluated for lethality and morphological changes.

Estradiol up-regulates estrogen receptor and progesterone receptor gene expression in specific ovine uterine cells.

The regulation of estrogen receptor (ER) and progesterone receptor (PR) genes is critical to estrogen and progesterone responsiveness of the uterus during the estrous cycle. A low dose of estradiol, given to ovariectomized ewes to mimic the preovulatory estrogen surge, acutely enhanced ER and PR gene expression in most uterine cells. Estradiol effects were measured at 12, 24, and 48 h post-injection (n = 6 ewes per time) with immunohistochemistry and in situ hybridization.

Media alternatives for the collection, culture and freezing of mouse and cattle embryos.

The replacement of biological products in media for the collection, culture and freezing of mammalian embryos was studied. To test the hypothesis that chemically defined surfactants can replace bovine serum albumin (BSA) or serum in embryo media, morula-stage mouse and cattle embryos were collected, cultured, and/or frozen in the surfactant compound, VF5. Collection efficiency of mouse and cattle embryos did not differ whether the medium contained serum or surfactant.