Superovulation without hormones - developing a novel, non-invasive method to induce follicular growth

转基因动物模型的建立，主要是小鼠和大鼠，彻底改变了我们对人类疾病的理解。转基因生物技术利用大量的动物：雌性和雄性都产生用于遗传操作的胚胎，雌性提供宿主子宫以支持转基因胚胎的发育，不育雄性在受体雌性中诱导所谓的“假孕”（雌性子宫接受移植胚胎的过程）。2017年，英国内政部对用于此类转基因育种计划的小鼠进行了169万次监管程序。因此，市场对既能提高手术效率，又能显著减轻实验动物痛苦的新技术有很大的需求。用于研究/育种计划的小鼠胚胎是通过一种称为超数排卵的方法从供体雌性产生的，其目的是最大限度地提高每只雌性的卵母细胞/胚胎产量。目前，该程序包括将激素注射到雌性小鼠的腹腔中，以刺激卵泡和卵子的生长。后者随后通过自然交配受精或收获并在体外受精。然而，成功的超数排卵本身是可变的，产量和质量在不同的操作者和激素批次之间存在差异。此外，腹腔内注射对动物来说是痛苦和令人苦恼的，使得使用者在3R原则下具有道德和法律的责任（“更换、减少、Ostara已经发现了一个市场机会，可以开发一种高质量的激素替代品，用于超排卵（使用称为适体的小分子）以及通过阴道递送其活性剂而远离腹腔内注射（这是使用当前激素治疗无法实现的）。这种新方法可以通过使用质量控制的定量激素替代品显着提高超排卵的可靠性，同时通过使用微创药物输送途径减少疼痛和痛苦。

The creation of genetically modified (transgenic) animal models, primarily mice and rats, has revolutionised our understanding of human disease. Transgenic biotechnologies utilise large numbers of animals: both females and males to generate embryos for genetic manipulation, females to provide a host uterus to support the development of transgenic embryos, and infertile males to induce so-called 'pseudopregnancy' (a process by which females' uterus becomes receptive to transferred embryos) in recipient females. In 2017, 1.69 million UK Home Office regulated procedures were conducted on mice destined for use in such transgenic breeding programmes. Therefore, there is a great market demand for new technologies which can both improve procedural efficiency and markedly reduce experimental animal pain and distress.Mouse embryos for research/breeding programmes are generated using donor females by a process known as superovulation, which aims to maximise oocyte/embryo yield per female. Currently, the procedure involves injecting hormones into the abdominal cavity of female mice to stimulate the growth of ovarian follicles and eggs. The latter are subsequently either fertilised through natural mating or harvested and fertilised in vitro. However, successful superovulation is inherently variable, with yields and quality varying across different operators and batches of hormones. Moreover, intra-abdominal injections are painful and distressing for animals such that users have an ethical and legal responsibility under the 3Rs principles ('Replacement, Reduction, Refinement') to use alternative methods if available.Ostara have identified a market opportunity for developing a high-quality replacement for the hormones used in superovulation (using small molecules called aptamers) as well as moving away from intra-abdominal injections by delivering their active agents vaginally (which is not achievable using current hormone treatments). This novel approach can significantly improve the reliability of superovulation through the use of quality-controlled metered dose hormone alternatives whilst reducing pain and distress by using a minimally invasive agent delivery route.