Ovarian dysfunction associated with zona pellucida-based immunocontraceptive vaccines

Despite more than 40 years of research into zona pellucida (ZP)-based vaccines, relatively little is known about their mechanism of action. Early research demonstrated precipitation of ZP glycoproteins by antiovarian antiserum, rendering oocytes resistant to sperm binding in vitro. Subsequent work showed significantly decreased fertilization rates following passive immunization, sparking interest in anti-ZP immunocontraception for human and animal use. The primary mechanism of action of ZP vaccines is generally considered to be an antibody-mediated interference with sperm-oocyte binding and/or fertilization. However, this mechanism of action excludes the potential for ovarian dysfunction associated with anti-ZP treatment in some species. A review of relevant literature in pertinent model, domestic and wildlife species reveals a variety of previous and current hypotheses for ovarian effects following ZP-based immunization. Ovarian dysfunction has been suggested to be a species-specific response. In addition, cytotoxic T-lymphocytes and the use of Freund's adjuvants have been suggested to play a role. Finally, the type and extent of glycosylation of ZP antigens have been proposed to influence ovarian effects. The validity of these hypotheses is re-examined in the light of current knowledge. Further investigation of ovarian function in species believed to be resistant to the ovarian effects of anti-ZP vaccines is warranted. To this end, anti-Milllerian hormone may provide a novel tool for the assessment of ovarian function during ZP-based immunocontraception, particularly in wildlife species not amenable to frequent clinical examination

Researching immunocontraceptive vaccines with mares (Equus caballus) as both a target and model for African elephant (Loxodonta africana) cows: a review

A sequence of studies is reviewed that reported the domestic horse (Equus caballus) mare as an appropriate and accessible research platform for recording clinical and laboratory data post-immunisation with anti- GnRH and -zona pellucida (ZP) immunocontraceptive vaccines. Experience with a native porcine ZP (pZP) vaccine in African elephant (Loxodonta africana) cows highlighted needs for improving vaccine formulations and more clearly defining associated ovarian effects and safety profiles. Initially, the efficacy, reversibility and safety of the GnRH vaccine Improvac® in mares was demonstrated using reproductive tract ultrasonography and concurrently measuring serum antibody titres and progesterone concentrations. Results informed the study design and minimally invasive monitoring of post-treatment ovarian steroid responses of this vaccine in free-ranging African elephant cows. A subsequent sequence of studies reported reversible contraceptive and immunological efficacy in pony mares immunised with pZP formulated with Freund’s adjuvants. By comparison, mares treated with a recombinant ZP3 and ZP4 (reZP) vaccine showed disappointing responses. Unexpectedly, most pZP-treated mares showed ovarian inactivity. In attempting to understand this response, results showed the involvement of cytotoxic (CD8+) T-cells negatively correlated to serum ovarian steroid and anti-Müllerian hormone (AMH) levels. Of concern was the prevalence of injection-site lesions ascribable to Freund’s adjuvants. Following this, mares treated with both pZP and a novel reZP vaccine formulated with non-Freund’s adjuvants showed comparable immunological responses and ovarian inactivity, notably without adverse treatment reactions. In addition, measuring AMH showed promise for monitoring ovarian function in anti-ZP-treated animals

Ovarian function in pony mares undergoing porcine zona pellucida immunocontraception

An advantage of the porcine zona pellucida (pZP) vaccine over other immunocontraceptives is the preservation of reproductive cyclicity and associated behaviors. Few studies have investigated ovarian function following pZP vaccination in the mare despite reported ovarian dysfunction in other species. The objectives of this study were to investigate ovarian function and estrous cyclicity in pony mares during immunocontraception with the conventional pZP vaccine. Fourteen mares were randomized into two groups of seven. Group I received 100 µg of pZP with Freund’s complete modified adjuvant (FCMA; V1), followed after five weeks by booster vaccination with 100 µg of pZP with Freund’s incomplete adjuvant (FIA; V2). Group II (controls) received two treatments five weeks apart of saline with FCMA (V1) and saline with FIA (V2) respectively. Treatments were administered via intramuscular injection into the gluteal muscles. Data were collected by an investigator blinded to treatment group over a period of 24 weeks during the physiological breeding season. All mares underwent estrus monitoring via trans-rectal palpation and ultrasound examination of the internal reproductive tract, on D0 (day of ovulation), D7, and D14 of consecutive estrous cycles, with daily monitoring between D14 and D0 of the following cycle. Artificial insemination was performed using fresh semen for up to two consecutive estrous cycles, commencing five weeks post-V2. Serum samples were collected weekly for the analysis of antibody titres and ovarian steroid (progesterone and estradiol) levels. Data were compared using Mann-Whitney U tests using commercially available software (IBM SPSS Statistics Version 22, International Business Machines Corp., Armonk, NY). Statistical significance was set as P < 0.05. All Group II mares showed normal estrous cyclicity throughout the study. Four Group I mares showed signs of anestrus within seven weeks of V2, characterised by small, inactive ovaries and baseline progesterone and estradiol levels. One Group I mare entered anestrus within 11 weeks of V2 and a second showed estrus with ovulation between variable periods of anestrus. Ovarian volumes, follicle counts and maximal follicle diameters in Group I were significantly lower than Group II. Per-cycle pregnancy proportions in Groups I and II were 0% and 78% respectively. This study demonstrated suppression of ovarian function in six of seven (86%) mares following pZP immunocontraception. Further research into the mechanism of action of zona pellucida-based vaccines is warranted

Thermal radiation in non-static curved spacetimes: quantum mechanical path integrals and configuration space topology

A quantum mechanical path integral derivation is given of a thermal propagator in non-static Gui spacetime. The thermal nature of the propagator is understood in terms of homotopically non-trivial paths in the configuration space appropriate to tortoise coordinates. The connection to thermal emission from collapsing black holes is discussed.Comment: 20 pages, major revised version, 9 figures, new titl

Tactics: Practical and Imagined

Since December 2017, a group of us (including Kim Solga, Sylvan Baker, Diana Damian Martin, Rebecca Hayes Laughton, and Katherine Low) have been convening working sessions at various schools and conferences that address the questions and problems animating this issue of RiDE. In this final article, a handful of our respondents from ASTR 2018 in San Diego ruminate upon, list, and re-member tactics they have used, or dreamed of using, to make it through the neoliberal academic day-to-day. Their thoughts are accompanied here by a handful of photos that document the documentation we produced at our first symposium

Comment Regarding the Functional Form of the Schmidt Law

Star formation rates on the galactic scale are described phenomenologically by two distinct relationships, as emphasized recently by Elmegreen (2002). The first of these is the Schmidt law, which is a power-law relation between the star formation rate and the column density. The other relationship is that there is a cutoff in the gas density below which star formation shuts off. The purpose of this paper is to argue that 1) these two relationships can be accommodated by a single functional form of the Schmidt law, and 2) this functional form is motivated by the hypothesis that star formation is a critical phenomenon, and that as a corollary, 3) the existence of a sharp cutoff may thus be an emergent property of galaxies, as was argued by Seiden (1983), as opposed to the classical view that this cutoff is due to an instability criterion.Comment: 14 pages, 3 figures, in press, New Astronomy. Figs provided in original (png) format as well as ps format for ps/pdf generatio