2015 SSR Meeting

2015 ABSTRACTS This document is to provide abstracts in a printable format. Sessions and topics have been indicated. Note that some abstracts may have been withdrawn since this documents creation on 2 June 2015. Please refer to one of the following online formats for complete time/date information and updates for the scientific program: SSR Web Site Schedule of Events and/or Scientific Program: http://www.ssr.org/15Schedule, http://www.ssr.org/15SciProgram Itinerary Builder: http://tinyurl.com/pxob8bf Invited and Short Oral Talks KEYNOTE 1. Re-conceiving the Pill: From Revolutionary Therapeutic to Lifestyle Drug. Elizabeth Watkins1. 1University of California, San Francisco, San Francisco, CA, USA This paper traces the shift in the conceptualization of the pill from life-changing to life-enhancing, from revolutionary to commonplace, and the implications for the trajectories of women, birth control, and pharmaceutical consumerism. In the 1960s, the birth control pill extended the reach of pharmacy beyond the treatment or prevention of disease or illness and effected a contraceptive revolution in the United States and in many other countries by changing the ways people thought about, discussed, and used birth control. Although much ink was spilled either crediting or blaming the pill for fomenting sexual revolution, it is clear from the historical record that the pill played only a supporting role as one of many factors contributing to the liberalization and democratization of sexual behaviors and attitudes. It played a similarly auxiliary part in the revolutionary appeal of second wave feminist activism that swept the United States in the late 1960s and 1970s. In concert with a host of other social, cultural, and political forces, the pill helped to make women’s lives in the 1980s look very different from those of their mothers in the 1950s. By the 1990s, the pill had become part of the birth control establishment, prescribed and used more often than any other method of reversible contraception. Well past its revolutionary heyday, it still served as the standard to which newer methods were compared. Manufacturers of oral contraceptives shifted the focus of their marketing strategies away from the primary indication of family planning to emphasize instead the secondary effects of relieving discomforts resulting from the menstrual cycle, such as pimples, irritability, and monthly bleeding. The transition in the pill’s social status – from a radically innovative drug that upended therapeutic and social conventions to an time-honored member of the pharmacopeia, considered so basic that it is marketed for its secondary effects – offers an interesting perspective for delineating the contours of this particular therapeutic revolution. STATE-OF-THE-ART LECTURES 2. Germ Line Modification to Create Large Animal Models of Human Disease. Ina Dobrinski1. 1Comparative Biology & Experimental Medicine, University of Calgary, Calgary, Alberta, Canada Genetically-modified domestic animal models are of increasing significance in biomedical research. Large animal models are especially valuable where rodent models do not recapitulate the phenotype observed in human patients as exemplified by animal models for cystic fibrosis. In addition, outbred large animal models are closer in size, physiology and longevity to humans than rodent models, thereby providing a more suitable platform for the development of treatment strategies.. With robust ES cells from domestic animals largely lacking, the currently established approaches for engineering genetic modifications in large animals are pronuclear microinjection and somatic cell nuclear transfer (SCNT or cloning). Both pronuclear microinjection and SCNT are relatively inefficient, costly, and time- consuming. In animals produced by pronuclear microinjection, the transgene is usually inserted randomly into the genome, which results in highly variable expression patterns and levels in different founders. Therefore, significant efforts are required to generate and screen multiple founders to obtain animals with optimal transgene expression. For SCNT, specific genetic modifications (both gain-of-function and loss-of- function) can be engineered and selected in the somatic cell nucleus before nuclear transfer. SCNT has been used to generate a variety of genetically modified animals such as goats, pigs, sheep and cattle; however, animals resulting from SCNT frequently suffer from developmental abnormalities associated with incomplete nuclear reprogramming. Other strategies to generate genetically-modified animals proposed the use of the spermatozoon as a natural vector to introduce genetic material into the female gamete. This sperm mediated DNA transfer (SMGT) combined with intracytoplasmatic sperm injection (ICSI) has reportedly relatively high efficiency but has not found widespread application. An approach developed to complement SCNT for producing genetically modified animals is germ cell 2015 Abstracts – Page 1 transplantation using genetically modified male germ line stem cells (GSCs). This approach relies on the ability of GSCs that are genetically modified in vitro to colonize the recipient testis and produce donor derived sperm upon transplantation. As the genetic change is introduced into the male germ line just before the onset of spermatogenesis, the time required for the production of genetically modified sperm is significantly shorter using germ cell transplantation compared to cloning or embryonic stem (ES) cell based technology. The GSC-mediated germ line modification also circumvents problems associated with embryo manipulation and nuclear reprogramming. Currently, engineering targeted mutations in domestic animals using GSCs remains a challenge as GSCs from those animals are difficult to maintain in vitro for an extended period of time. Recent advances in genome editing techniques such as Zinc-Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) greatly enhance the efficiency of engineering targeted genetic change in domestic animals as demonstrated by the generation of several gene knock- out pig and cattle models using those techniques. The potential of GSC-mediated germ line modification in making targeted genetic modifications in domestic animal models will be maximized if those genome editing techniques can be applied in GSCs. 3. MicroRNA Evolution and Function. David Bartel1. 1 HHMI/MIT/Whitehead Institute, Cambridge, MA, USA We study the molecular pathways that regulate eukaryotic gene expression by affecting the stability or translation of mRNAs. Much of our work is on microRNAs (miRNAs), which are ~22 nt RNAs that pair to sites within mRNAs to direct the posttranscriptional down-regulation of these messages. Because most human mRNAs are conserved regulatory targets of miRNAs, it will be hard to find a developmental or physiological process that is not influenced by miRNAs. For example, when the mRNAs of Zeb transcription factors are altered such that the miR-200 family of miRNAs can no longer repress them, female mice are sterile because they do not ovulate. We also study mRNAs, with particular interest in the untranslated regions and poly(A) tails, and how these regions recruit and mediate regulatory phenomena. We have developed a high-throughput method to measure the lengths of miRNA poly(A) tails. When we used this method to measure tail lengths of millions of individual mRNAs isolated from early zebrafish and frog embryos, we found a very strong correlation between tail length and translational efficiency, as would be expected if mRNAs with longer tails were more efficiently translated. However, this strong coupling diminished at gastrulation and was absent in nonembryonic samples, which indicated a previously unrecognized developmental switch in the nature of translational control. DIVERSITY SYMPOSIUM 4. Maternal Vitamin D Deficiency Programs Hypothalamic-Pituitary Dysfunction and Subfertility in Affected Female Offspring. Genevieve Neal-Perry1, Cari Nicholas2, Andrew Wolfe3, Thomas Fisher4, Joseph Davis5, Yan Sun1. 1Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA; 2Department of Molecular and Cell Biology, Einstein College of Medicine, Bronx, NY, USA; 3Department of Pediatrics, John Hopkin’s Medical School, Baltimore, MD, USA; 4Department of Obstetrics and Gynecology, Washington State University, Spokane, WA, USA; 5Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA Vitamin D (VD) deficiency affects over one billion people worldwide. In the Unites States, as much as 40% of pregnant women and 20% of children are VD deficient. The vitamin D receptor (VDR) is expressed throughout the hypothalamic-pituitary-gonadal (HPG) axis raising the possibility that VDR signaling is an important regulator of HPG function and reproduction. We previously reported female mice exposed to peripubertal VD deficiency have delayed puberty and develop estrous cycle dysfunction in adulthood that is rescued by dietary VD supplements. To determine the critical developmental periods during which VD deficiency might affect reproductive function in adult female mice and program subfertility in affected offspring, we exposed female mice to dietary VD deficiency at three specific developmental stages: 1) in utero, 2) lactation or 3) in utero and lactation (early life). We hypothesize that in utero VDR signaling is necessary for normal

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