Detection of sperm antigens on mouse ova and early embryos

Serum and colostrum antibodies against mouse sperm were developed in two rabbits after systemic and mammary gland immunizations. Indirect immunofluorescence utilizing fluorescein-labeled goat antisera against rabbit IgG and IgA, respectively, indicated that both immune serum (IS) and colostrum (IC) compared with control samples caused intensive staining of the acrosome and tail of sperm. Absorption of IS and IC with mouse serum and the spleen, kidney, liver, and brain of male mice did not reduce the strength or the pattern of staining reaction on sperm. The absorbed IS reacted with cell surfaces of oocytes, unfertilized ova, zygotes, two-cell and four- to eight-cell fertilized ova, and blastocysts. The absorbed IC, however, reacted only with the four- to eight-cell embryo and blastocyst. Further absorption of the IS with mouse ovary removed the reaction with unfertilized ova and the one- to two-cell fertilized ova, but the staining of later embryo stages was unaffected. Therefore, it appears that specific rabbit anti-sperm antibodies are detecting two cell-membrane antigens on mouse embryos: one originating from the ovary and the other arising after fertilization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22638/1/0000189.pd

Identification of Human Sperm Antigens to Antisperm Antibodies *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98396/1/j.1600-0897.1983.tb00243.x.pd

Absence of Antisperm Antibodies in Anejaculatory Men

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96435/1/j.1939-4640.1990.tb00162.x.pd

Reduction of fertility in female rabbits and mice actively immunized with a germ cell antigen (GA-1) from the rabbit

Female rabbits and mice were actively immunized against germ cell antigen (GA-1) of 63 kDa molecular mass isolated from rabbit sperm and testis. There was a significant (P P < 0.01) reduction in fertility as seen by mean 7-9 day implants+/-S.D. per mated mouse actively immunized with GA-1 whether through the intraperitoneal route (GA-1, 1.2+/-1.6; controls, 8.0+/-3.4) or through the subcutaneous/intramuscular route (GA-1, 3.8+/-3.4; controls, 10.1+/-3.9). The antisera from these actively immunized animals were negative for sperm agglutinating and immobilizing antibodies. In the Western blot enzyme-immunobinding procedure, the antisera showed specific binding to a single protein of 63 kDa. The incidence of fertilization of eggs recovered from rabbits inseminated with anti-GA-1 antibodies-treated sperm was not significantly different from control rabbits. The percentage of fertilized eggs obtained from rabbits inseminated with anti-GA-1 antibodies-treated sperm that reached the blastocyst stage upon in vitro incubation, however, was significantly less than that for embryos obtained from rabbits inseminated with control serum-treated sperm. Incubation of normal fertilized eggs in vitro with the antibodies did not affect development. Neither antiserum nor immune uterine fluid reacted with 4-day blastocysts in the indirect immunofluorescence technique. It is concluded that active immunization with GA-1 results in post-fertilization reduction of fertility in rabbits and mice by inhibiting early embryonic development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25986/1/0000052.pd

Monoclonal antibodies to human sperm antigens

To elucidate the molecular nature of human sperm autoantigens, attempts were made to raise monoclonal antibodies against these antigens by hybridoma techniques. After successive immunizations with the particulate fractions of human sperm extract in BALB/c mice, the spleen cells were fused with P3-X63-Ag8 myeloma cells. Several clones and their subclones were obtained and shown by microplate radioimmunoassay to produce antibodies against human sperm antigens. When SDS gel/protein blot radioimmunobinding was used for further molecular analysis, three independently derived clones were shown to produce antibodies, all of which cross-reacted with the same two human sperm antigens with a molecular weight of about 10 000. Using an indirect immunofluorescence assay, antibodies produced by these clones were shown to react with antigens localized on the acrosomal regions of human spermatozoa. Monoclonal antibodies produced by other clones, however, showed no cross-reactivity with any of the blotted proteins from SDS gels of human spermatozoa. Some possible reasons for this are presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23934/1/0000180.pd

Combined electroejaculation and in vitro fertilization in the evaluation and treatment of anejaculatory infertility

Seven couples underwent combined electroejaculation and in vitro fertilization for anejaculatory infertility after a failed regimen of electroejaculation and intrauterine insemination. Two pregnancies resulted, one proceeding to a term vaginal delivery and one ending in a 6-week spontaneous abortion. Poor sperm binding and no fertilization were seen in two of the couples. Fertilization of the oocytes but no subsequent pregnancy were seen in the other three couples. Combined in vitro fertilization and gamete intrafallopian transfer was performied in four of the couples. The combination of electroejaculation and in vitro fertilization offers the opportunity to evaluate the female pelvis, observe the sperm-oocyte interaction, and achieve a pregnancy in couples with anejaculatory infertility.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44644/1/10815_2005_Article_BF01133886.pd

Influenza Virus Infection of the Murine Uterus: A New Model for Antiviral Immunity in the Female Reproductive Tract

Secretory IgA (S-IgA) mediates local immunity to influenza virus in the murine upper respiratory tract and may play an important role in local immunity to various microorganisms in the female reproductive tract as well. Although the presence of IgA in cervicovaginal or uterine secretions has been correlated with immunity to a number of pathogens, there has been no direct demonstration of the mediation of uterine antiviral immunity by S-IgA. Influenza virus, although not a normal pathogen of the reproductive tract, was used to develop a model for the investigation of mucosal immunity in the uterus. PR8 (H1N1) influenza virus injected into the ovarian bursa of BALB/c mice grew well, with peak titers between days 3 and 5. Intravenous injection of polymeric IgA anti-influenza virus monoclonal antibody before or 30 min after viral challenge protected mice against viral infection. We believe this work to be the first direct demonstration of S-IgA-mediated antiviral uterine immunity. It provides a model for further investigation of immunity in the female reproductive tract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63226/1/vim.2006.19.613.pd

Utilizing CryoSat-2 sea ice thickness to initialize a coupled ice-ocean modeling system

Two CryoSat-2 sea ice thickness products derived with independent algorithms are used to initialize a coupled ice-ocean modeling system in which a series of reanalysis studies are performed for the period of March 15, 2014–September 30, 2015. Comparisons against moored upward looking sonar, drifting ice mass balance buoy, and NASA Operation IceBridge ice thickness data show that the modeling system exhibits greatly reduced bias using the satellite-derived ice thickness data versus the operational model run without these data. The model initialized with CryoSat-2 ice thickness exhibits skill in simulating ice thickness from the initial period to up to 6 months. We find that the largest improvements in ice thickness occur over multi-year ice. Based on the data periods examined here, we find that for the 18-month study period, when compared with upward looking sonar measurements, the CryoSat-2 reanalyses show significant improvement in bias (0.47–0.75) and RMSE (0.89–1.04) versus the control run without these data (1.44 and 1.60, respectively). An ice drift comparison reveals little change in ice velocity statistics for the Pan Arctic region; however some improvement is seen during the summer/autumn months in 2014 for the Bering/Beaufort/Chukchi and Greenland/Norwegian Seas. These promising results suggest that such a technique should be used to reinitialize operational sea ice modeling systems

The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Species

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction