Elevated progesterone in yolk as a moderator of prenatal and postnatal auditory learning in bobwhite quail

Recent studies have established that yolk hormones of maternal origin have significant effects on the physiology and behavior of offspring in birds. Herrington (2012) demonstrated that an elevation of progesterone in yolk elevates emotional reactivity in bobwhite quail neonates. Chicks that hatched from progesterone treated eggs displayed increased latency in tonic immobility and did not emerge as quickly from a covered location into an open field compared to control groups. For the present study, three experimental groups were formed: chicks hatched from eggs with artificially elevated progesterone (P), chicks hatched from an oil-vehicle control group (V), and chicks hatched from a non-manipulated control group (C). Experiment 1 examined levels of progesterone with High Performance Liquid Chromatography/tandem Mass Spectroscopy (HPLC/MS) from prenatal day 1 to prenatal day 17 in bobwhite quail egg yolk. In Experiment 2, bobwhite quail embryos were passively exposed to an individual maternal assembly call for 24 hours prior to hatching. Chicks were then tested individually for their preference between the familiarized call and a novel call at 24 and 48 hours following hatching. For Experiment 3, newly hatched chicks were exposed to an individual maternal assembly call for 24-hrs. Chicks were then tested for their preference for the familiarized call at 24 and 48-hrs after hatch. Results of Experiment 1 showed that yolk progesterone levels were significantly elevated in treated eggs and were present in the egg yolk longer into prenatal development than the two control groups. Results from Experiment 2 indicated that chicks from the P group failed to demonstrate a preference for the familiar bobwhite maternal assembly call at 24 or 48-hrs after hatch following 24-hrs of prenatal exposure. In contrast, chicks from the C and V groups demonstrated a significant preference for the familiarized call. In Experiment 3, chicks from the P group showed an enhanced preference for the familiarized bobwhite maternal call compared to chicks from the C and V groups at 24 and 48-hrs after hatch. The results of these experiments suggest that elevated maternal yolk hormone levels in pre-incubated bobwhite quail eggs can influence auditory perceptual learning in embryos and neonates.^

Reduced Androgen Receptor Expression Accelerates the Onset of ERBB2 Induced Breast Tumors in Female Mice

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining the floxed allele of Ar with the MMTV-cre transgene on an MMTV-NeuNT background and compared them to littermate MMTV-NeuNT, Arfl/+ control females. Heterozygous MARKO females displayed reduced levels of AR in mammary glands with mosaic AR expression in ductal epithelium. The loss of AR dramatically accelerated the onset of MMTV-NeuNT tumors in female MARKO mice. In this report we show that accelerated MMTV-NeuNT-dependent tumorigenesis is due specifically to the loss of AR, as hormonal levels, estrogen and progesterone receptors expression, and MMTV-NeuNT expression were similar between MARKO and control groups. MMTV-NeuNT induced tumors in both cohorts displayed distinct loss of AR in addition to ERα, PR, and the pioneer factor FOXA1. Erbb3 mRNA levels were significantly elevated in tumors in comparison to normal mammary glands. Thus the loss of AR in mouse mammary epithelium accelerates malignant transformation rather than the rate of tumorigenesis.