Octylphenol (OP) is one of a number of compounds found in the environment that has estrogen-mimicking actions in vivo. Our objective was to determine if maternal exposure to octylphenol during fetal and/or postnatal life would affect the onset of puberty, endocrine status, and subsequent ovarian follicular dynamics of ewe lambs. Lambs were born in March to ewes that received twice weekly s.c. injections of octylphenol (1000 micro g/kg/day) from Day 70 of gestation to weaning (n = 6); Day 70 of gestation to birth (n = 3); birth to weaning (n = 5; gestation = 145 days); or corn oil from Day 70 of gestation to weaning (control; n = 5). Blood samples were collected twice weekly to determine progesterone and FSH concentrations from 20 wk of age throughout the first breeding season. Onset of puberty and interestrous intervals were determined from 20 wk of age by twice daily observation for estrus in the presence of a vasectomized ram. During January the ovaries of each lamb were examined using transrectal ultrasonography from the day of estrus for 15 days. Blood samples were collected every 8 h to examine FSH concentrations and every 2 h to detect the preovulatory gonadotropin surge throughout this estrous cycle. The onset of puberty and first progesterone rise was advanced and the FSH preovulatory surge was elevated for longer in the OP-treated lambs compared with the control lambs (P < 0.05). Interestrous intervals, FSH profiles, and ovarian follicular dynamics were not affected (P > 0.05) by exposure to octylphenol. In conclusion, octylphenol exposure advanced the onset of puberty but it did not disrupt FSH concentrations or the dynamics of ovarian follicular growth.

PrPc is a normal cell‐surface glycoprotein that is conformationally characterized by two alpha helices and two complex‐type N‐linked oligosaccharide chains. This protein is unique in its propensity to misfold into a neurodegenerative disease‐causing proteinaceous infectious particle, known as a prion. PrPc can undergo conversion into PrPSc through spontaneous misfolding, a genetic mutation of the human PRNP gene, or exposure to a prion from an external source. When this happens, its composition shifts from an alpha‐helical, soluble protein low in beta pleated sheets to an insoluble, protease‐resistant particle with a high percentage of beta sheets. This resulting misfolded form, known formally as PrPSc, is pathogenic and aggregates in neural tissue by recruiting and converting more PrPc to PrPSc, ultimately causing neuronal cell dysfunction followed by cell death. The prion's form of “self‐replication” without utilizing genetic material is particularly fascinating, as it appears to defy the central dogma of biology and differs from all other pathogenic particle infection mechanisms. It is notable that some prions have evolved to act as transmissible infectious agents, similar to viruses, despite the absence of genetic material. This distinguishes some prion diseases, such as chronic wasting disease (CWD) and scrapie, from their inherited disease counterparts. The biosynthesis pathway of PrPc is similar to other cellular proteins, with replication occurring on the ribosomes on the endoplasmic reticulum. However, whereas malfunctioning proteins are normally tagged by ubiquitin and then degraded in a proteasome, the ubiquitin‐proteasome complex is inhibited during prion formation, allowing PrPSc to form and survive degradation, leading to its buildup in cytosol and subsequent neurotoxicity. Human and animal prion diseases have been classified into three broad categories‐‐genetic, sporadic, and acquired‐‐based on properties of the PrP proteins and prion infection morphology. Physical symptoms of prion infection include deviant behavior, dementia, ataxia, insomnia, paraplegia, and paresthesias. Commonly discussed prion‐induced diseases (differentiated via host type and slight conformational discrepancies between misfolded proteins) include scrapie, kuru, CJD, bovine spongiform encephalopathy (mad cow disease), and CWD. Here, we present current research on prions, with a focus on CWD, which was first found in Colorado and affects deer and other cervids.The Olathe North High School Team 1 MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationships and histology of PrPc, or the normal cellular prion.Support or Funding InformationThis project is a joint venture between the Milwaukee School of Engineering and the Medical Professions Academy.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Follicle‐stimulating hormone (FSH) is a member of the glycoprotein hormone (GPH) family. It is secreted by gonadotropes, which are found in the anterior pituitary gland. FSH is an important hormone for the production and development of gametes in both men and women. The hormone is a part of a cascade that begins with the release of gonadotropin‐releasing hormone that is released from the hypothalamus and stimulates gonadotropes in the pituitary gland. These stimulated gonadotropes release FSH and the luteinizing hormone (LH) into the bloodstream where they travel through the bloodstream to the gonads. In males, FSH stimulate the Sertoli cells to produce a ABP, or androgen‐binding protein, and inhibin. ABP keeps testicular testosterone concentrations elevated for spermatogenesis, while inhibin feeds back to the anterior pituitary to cease production of FSH. LH stimulates testicular Leydig cells to synthesize and secrete testosterone. In females, FSH stimulates ovarian follicular granulosa cells to continue to grow and divide, secrete estradiol, and become responsive to LH stimulation. LH stimulates ovarian theca cells to produce the androgen precursor converted to estradiol by granulosa cells. The LH surge triggers ovulation and LH stimulates progesterone synthesis and release by the corpus luteum during the luteal phase of the menstrual cycle. FSH binds to the FSH receptor (FSHR) to stimulate cellular responses. The FSHR is a G protein‐coupled receptor (GPCR) that possesses an exceptionally large N‐terminal ectodomain composed of leucine‐rich repeats. Glycoprotein hormones, which FSH is member, are identified by a common alpha‐ and hormone‐specific beta‐subunit heterodimeric structure. The alpha‐subunit peptide sequence and disulfide bond pattern are consistent throughout all glycoprotein hormones. The beta‐subunit is what dictates the function of the hormone and dictates binding to the cognate receptor. The alpha and beta subunits are folded into non‐globular, cystine knot structures with three loops extending from the core motif, which consists of three disulfide bridges. An additional peptide emerges from the beta subunit and wraps around the L2 loop of the alpha subunit in a manner similar to a seatbelt. The seatbelt loop possesses the hormone‐specific determinants of the FSH beta‐subunit. FSH binds to the FSHR. Current research is focused on the effect of FSH glycosylation variations on the activation of the receptor.Support or Funding InformationThis is a SMART Team project supported through the contributions of Dr. George R. Bousfield of Wichita State University, the Milwaukee School of Engineering, and the Olathe Medical Professions 21st Century Academy.

Concerns have been raised about the potential adverse effects on reproductive health in farm animals, humans, and wildlife species from a range of environmental chemicals that disrupt normal hormonal actions. The alkylphenol polyethoxylates are non-ionic surfactants used in the manufacture of detergents, paints and herbicides. During sewage treatment, these compounds are broken down to short chain alkylphenol polyethoxylates, alkylphenol carboxylic acids and alkylphenols which bioaccumulate in the lipid of living organisms. The estrogenic nature of one of these compounds - octylphenol has been clearly demonstrated in cell culture, in a recombinant yeast screen with human estrogen receptor?and in animal studies. It is proposed that these endocrine disrupting compounds influence male adult reproductive potential by disrupting the development of the hypothalamic-pituitary-testicular axis during fetal life. We have recently identified that exposure to octylphenol for the second half of gestation decreases circulating concentrations of FSH during fetal life and the number of Sertoli cells of the testis and testis size at birth in comparison to control animals (Sweeney et al., 2000). However, the testes size, % interstitial space, semen volume, semen concentration and % live semen was similar in both treatment groups in the adult. In contrast animals exposed to octylphenol from birth to weaning (16 weeks of age) had a significantly greater number of primary and secondary abnormalities in comparison to controls and animals exposed to octylphenol for the second half of gestation. A number of the animals exposed to octylphenol from birth to weaning exhibited augmented sexual behaviour, while those exposed to octylphenol for the second half of pregnancy showed a suppression of sexual behaviour. The current data suggests the physiological effect of exposure to octylphenol is dependant on the time and duration of exposure. This has major implications for the determination of universal end-point measurements to assess exposure to endocrine disrupting compounds.