model, Lecithin: Retinol Acyltransferase (LRAT) knockout (KO) mouse was used to answer our question. METHODS: 9 LRAT KO animals were fed either Vitamin A sufficient (ASuf) or Vitamin A deficient (ADef) diets for 8wks, with the latter known to produce SCO. H&E of testicular slides was used to assess histology. Immunofluorescence (IF) with antibodies against SYCP3 (marker of spermatocytes) was used to confirm loss of meiotic cells in LRAT KO Adef mice. RNAseq and smallRNA sequencing was performed using total RNA extracted from testes. Sequencing results were processed using JMP Genomics. Expres- sion levels of GFRa1, PLZF, SCYP3, PRM1, TNP, CLU, and VIM were used to evaluate loss of different germ cell populations in the Adef group, and to normalize the data to the number of Sertoli cells. MicroRNA202-5p expression (Sertoli specific), miR-34c (germ cell specific) and let-7 (ubiquitous) were measured from sequencing data and further confirmed using QRT-PCR. Results were statistically significant at FRD¼0.01 RESULTS: 3 mice were evaluated in each respective group, LRAT Asuf and ADef conditions, at both 6 and 8wk time points. His- tology, IF, and sequencing data demonstrated that spermatogenesis was present in all groups except for LRAT ADef mice at 8 weeks. Histology revealed heterogeneity, with most tubules resembling SCO in LRAT ADef testes. Normal spermatogenesis was observed in LRAT KO Asuf mice, and hypo spermatogenesis was observed in LRAT KO ADef mice at 6wks. There was no significant change in expression levels of miR202-5p between LRAT ASuf an ADef groups at 8wks. However, expression of miR34c was significantly decreased in the LRAT Adef group. Let-7 expression remained same. CONCLUSIONS: Loss of meiotic germ cells in LRAT KO ADef mice did not result in loss of miRNA-202-5p expression when compared to controls despite development of predominantly SCO histology. Our results provide strong evidence that the observed loss of expression of miRNA202-5p in men with SCO is not due to the primary loss of germ cells but is a result of primary miRNA-202-5p dysfunction in Sertoli cells. Source of Funding: This work was supported by: P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation; Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund PD08-08 S-NITROSOGLUTATHIONE REDUCTASE (GSNOR) KNOCKOUT MICE: A NOVEL MODEL OF MALE INFERTILITY Shathiyah Kulandavelu, Marilia Sanches Santos Rizzo Zutti, HIMANSHU ARORA, Oleksandr Kryvenko, Emad Ibrahim, Nancy L Brackett, Joshua M. Hare, Ranjith Ramasamy*, MIAMI, FL INTRODUCTION AND OBJECTIVES: Nitrosative stress is regulated by S-nitrosylation of cysteine thiols. Mice lacking S-nitro- soglutathione reductase (GSNOR KO mice), a denitrosylase that regulates S-nitrosylation, show increased levels of S-nitroslyated proteins and exhibit nitrosative stress. Nitrosative stress, similar to oxidative stress, can affect spermatogenesis. We hypothesized that GSNOR KO male mice will exhibit impaired fertility and spermatogenesis. METHODS: Male wild-type (WT) and GSNOR KO mice (N¼6 each) were studied after postnatal day 42, at a stage where they have completed the first wave of spermatogenesis. Testes were either fixed and/or frozen for further analysis. Histology of testes was quantified using Johnsen score, epididymal sperm counts was determined using an automated counter, serum testosterone levels was determined using ELISA and GSNOR protein within the testis was evaluated using immunofluorescence and Western blot analysis. RESULTS: GSNOR KO males exhibited significantly smaller testes as compared to WT (0.1Æ 0.0 grams vs. 0.07Æ 0.0 grams, p<0.05). Furthermore, serum testosterone levels was significantly lower in the GSNOR KO as compared to WT mice (370.18 Æ 0.0ng/mL vs. 42.55 Æ 21.7 ng/mL, p<0.05). Histological analyses using Johnsen score of GSNOR KO testes showed evidence of degeneration of seminiferous tubules, overall reduction in post- meiotic cells and disrupted spermatogenesis (9.5 vs. 6.5, p<0.05). We observed a ~2-fold reduction in epididymal sperm count in GSNOR KO males compared to WT males, indicating that sper- matogenesis was impaired, but not globally arrested (2054 Æ 35.35 sperms vs. 1236 Æ 86.26 sperms, p<0.05). Wild type testis showed extremely high levels of GSNOR protein expressed in the germ cells as well as Leydig cells. CONCLUSIONS: This is the first study demonstrating the as- sociation between GSNOR and male fertility. GSNOR KO males exhibit small testes with impaired spermatogenesis and reduced fertility. At- tempts to decrease nitrosative stress can reverse impaired spermatogenesis. Source of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award Program to RR PD08-09 HOW DOES ADVANCED PATERNAL AGE AFFECT THE NEXT GENERATION? Jiang Zhu, Xin Li*, Rochester, NY INTRODUCTION AND OBJECTIVES: Older fathers have a significantly higher chance of generating offspring with a high preva- lence of genetic abnormalities, childhood cancers, and neuropsychiatric disorders, including schizophrenia, autism, and bipolar disorder (1). We know very little about how paternal aging affects future generations or why certain syndromes are particularly susceptible to the paternal-age effect. A recent trend toward delayed paternity (in the US, births to fa- thers over 40 years has risen from 7.5% in 1992 to 10.1% in 2000 (2)) and a widespread use of assisted reproductive technologies (which resulted in 61,610 US infants in 2011 (3)) makes it imperative for our species to understand how aging effects germ cells and how paternal factors affect the next generation. The current studies on paternal aging are mostly descriptive and we lack animal models to address the mechanisms. METHODS: While a diverse pool of RNAs exists in sperm, it was the dogma that only sperm contribute DNA to the next generation. However, recent studies have shown that the effects of an animal’s environment, such as traumatic stress and high fat diet, during adolescence can be passed down to the next generation through sperm RNAs(4e6). In this study, we sequenced both small RNAs (miRNAs and piRNAs) and long RNAs (mRNAs, transposable elements, and non-coding RNAs) from sperm of C57/B6 wild-type mice of the ages 8 weeks, 15 months and 21 months. RESULTS: We detected a distinct miRNA profile during paternal aging and an age-dependent decrease in RNA surveillance for transposable elements in male germ cells. CONCLUSIONS: In conclusion, the sperm RNA changes can be used as biomarkers to evaluate the aging process in old males. We envision that this work will pave the way for further studies on sperm RNA transgenerational effects. Reference 1. D. Malaspina, C. Gilman, T. M. Kranz, Fertil Steril 103, 1392 (2015). 2. M. King, P. Bearman, Int J Epidemiol 38, 1224 (2009). 3. S. Sunderam et al., MMWR Surveill Summ 63, 1 (2014). 4. K. Gapp et al., Nat Neurosci 17, 667 (2014). 5. U. Sharma et al., Science 351, 391 (2016). 6. Q. Chen et al., Science 351, 397 (2016). Vol. 197, No. 4S, Supplement, Friday, May 12, 2017 THE JOURNAL OF UROLOGY â e191