Hansen Peter J, Soto Paolete, Natzke Roger P
Department of Animal Sciences, University of Florida, Gainesville, FL, USA.
Am J Reprod Immunol. 2004 Apr;51(4):294-301. doi: 10.1111/j.1600-0897.2004.00160.x.
Causes for pre-implantation embryo loss, which can be as high as 50% or more of fertilized embryos, are multifactorial and largely undescribed. Studies in cattle using mastitis as a model indicate that one cause of early embryonic loss is infectious disease or activation of immune responses at sites outside the reproductive tract. Infection of the mammary gland in dairy cattle is associated with a reduction in pregnancy rate (proportion of inseminated cows that become pregnant) and an increase in the number of inseminations required to establish pregnancy. Also, intravenous challenge with bacterial peptidoglycan and polysaccharide at approximately days 3-5 after breeding reduced subsequent pregnancy rate in sheep that had been previously immunized against the same material. The mechanism by which extrauterine activation of immune and inflammatory responses leads to embryonic loss is not clear although cytokines probably play a crucial role. Effects could be exerted at the level of the hypothalamic-pituitary axis, ovary, reproductive tract or embryo. Interferon (IFN)-alpha, for example, which can reduce pregnancy rate in cattle when injected around 13-19 days after breeding, increases body temperature, inhibits secretion of luteinizing hormone, and reduces circulating concentrations of progesterone. Other cytokines or products of cytokine activation could cause embryonic loss by causing hyperthermia (as elevated temperature blocks oocyte function and embryonic development), exerting toxic effects on the corpus luteum [for example, IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and prostaglandin F(2alpha)], stimulating endometrial prostaglandin synthesis [TNF-alpha and interleukin(IL)-1beta], reducing endometrial cell proliferation (IL-1beta), and interfering with oocyte maturation and embryonic development (TNF-alpha, nitric oxide, and prostaglandin F(2alpha)). Although largely neglected by reproductive immunologists, study of the involvement of the immune system in pre-implantation embryonic loss is likely to lead to new methods for enhancing fertility.
植入前胚胎丢失的发生率可能高达受精胚胎的50%或更高，其原因是多因素的，且在很大程度上尚未明确。以乳腺炎为模型的牛研究表明，早期胚胎丢失的一个原因是生殖道外部位的传染病或免疫反应激活。奶牛乳腺感染与妊娠率降低（授精母牛怀孕的比例）以及建立妊娠所需的授精次数增加有关。此外，在配种后约3 - 5天静脉注射细菌肽聚糖和多糖会降低先前已针对相同物质进行免疫的绵羊的后续妊娠率。尽管细胞因子可能起关键作用，但子宫外免疫和炎症反应激活导致胚胎丢失的机制尚不清楚。其影响可能作用于下丘脑 - 垂体轴、卵巢、生殖道或胚胎水平。例如，在配种后约13 - 19天注射时可降低牛妊娠率的干扰素（IFN） - α会升高体温、抑制促黄体生成素的分泌并降低孕酮的循环浓度。其他细胞因子或细胞因子激活产物可能通过引起体温过高（因为升高的温度会阻断卵母细胞功能和胚胎发育）、对黄体产生毒性作用（例如，IFN - γ、肿瘤坏死因子 - α（TNF - α）和前列腺素F（2α））、刺激子宫内膜前列腺素合成（TNF - α和白细胞介素（IL） - 1β）、减少子宫内膜细胞增殖（IL - 1β）以及干扰卵母细胞成熟和胚胎发育（TNF - α、一氧化氮和前列腺素F（2α））而导致胚胎丢失。尽管生殖免疫学家很大程度上忽略了这一点，但研究免疫系统在植入前胚胎丢失中的作用可能会带来提高生育力的新方法。
