Fray M D, Mann G E, Clarke M C, Charleston B
Institute for Animal Health, Embryology Group, Division of Environmental Microbiology, Compton, Newbury, RG20 7NN, Berkshire, UK.
Vet Microbiol. 2000 Nov 15;77(1-2):185-94. doi: 10.1016/s0378-1135(00)00275-3.
Bovine viral diarrhoea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. In this paper we investigate how BVDV interacts with the ovary. The viruses' tropism for the pre-ovulatory oocyte was studied by indirect immunohistochemistry. Two monoclonal antibodies, raised against the non-structural protein NS3 and the envelope glycoprotein E2 were used to probe cryo-sections cut from the ovaries of three persistently infected heifers. NS3 and E2 antigens were widely distributed within the ovarian stroma and follicular cells. NS3 was also localised within the proportion of oocytes. Overall 18.7% of the oocyte population had detectable levels of NS3. What is more, the proportion of antigen positive oocytes remained constant (P>0. 05) throughout the different stages of oocyte maturation. In a subsequent study seven cows were challenged with non-cytopathogenic BVDV (strain Pe515: 5x10(6) TCID(50)) to determine the oestradiol and progesterone responses to an acute infection. The sensitivity of the endogenous luteolytic mechanism was also established by analysing plasma prostaglandin F2alpha metabolite (PGFM) levels following an exogenous oxytocin (50 IU) challenge. The inoculation was given 2 days before a synchronised oestrus and was timed to ensure that viraemia occurred during the initial stage of corpora luteal development. Seven cows inoculated with non-infectious culture medium served as control animals and remained BVDV naive throughout the study. The BVDV challenge was followed by leucopenia, viraemia and sero-conversion. The virus also significantly (P<0.01) reduced plasma oestradiol levels between day 6 and day 11 post-inoculation (i.e. between day 4 and day 9 post-oestrus). However, the infection did not alter (P>0.05) progesterone secretion throughout the oestrous cycle or the plasma concentration of PGFM. These data indicate that bovine follicular cells and oocytes are permissive to BVDV at all stages of follicular development. They also show that a transient fall in oestradiol secretion may accompany an acute infection. In conclusion, this work has identified two potential routes through which BVDV can reduce fertility in the cow, namely impairment of oocyte quality and disruption of gonadal steroidogenesis.
牛病毒性腹泻病毒（BVDV）是一种主要的牛病原体，可导致一系列症状，包括繁殖障碍。在本文中，我们研究了BVDV与卵巢的相互作用。通过间接免疫组织化学研究了该病毒对排卵前卵母细胞的嗜性。使用两种针对非结构蛋白NS3和包膜糖蛋白E2产生的单克隆抗体，对从三头持续感染的小母牛卵巢切取的冷冻切片进行检测。NS3和E2抗原广泛分布于卵巢基质和卵泡细胞中。NS3也定位于一定比例的卵母细胞内。总体而言，18.7%的卵母细胞群体有可检测水平的NS3。此外，在卵母细胞成熟的不同阶段，抗原阳性卵母细胞的比例保持恒定（P>0.05）。在随后的一项研究中，用非细胞病变性BVDV（毒株Pe515：5×10⁶ TCID₅₀）攻击7头母牛，以确定急性感染后的雌二醇和孕酮反应。通过分析外源性催产素（50 IU）攻击后血浆前列腺素F2α代谢物（PGFM）水平，也确定了内源性黄体溶解机制的敏感性。接种在同步发情前2天进行，并且安排时间以确保在黄体发育的初始阶段发生病毒血症。7头接种非感染性培养基的母牛作为对照动物，在整个研究过程中保持未感染BVDV。BVDV攻击后出现白细胞减少、病毒血症和血清转化。该病毒在接种后第6天至第11天（即发情后第4天至第9天）之间也显著（P<0.01）降低了血浆雌二醇水平。然而，感染在整个发情周期中并未改变（P>0.05）孕酮分泌或PGFM的血浆浓度。这些数据表明，在卵泡发育的所有阶段，牛卵泡细胞和卵母细胞对BVDV均具有易感性。它们还表明，急性感染可能伴随雌二醇分泌短暂下降。总之，这项研究确定了BVDV降低母牛繁殖力的两条潜在途径，即卵母细胞质量受损和性腺类固醇生成紊乱。
