The Acute Phase Protein Ceruloplasmin as a Non-Invasive Marker of Pseudopregnancy, Pregnancy, and Pregnancy Loss in the Giant Panda

After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20–24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion.

排卵后，未受孕的雌性大熊猫会出现假妊娠（pseudopregnancy）现象。在假妊娠期间，未受孕个体可表现出与妊娠状态相似的生理与行为变化。对于多数会经历假妊娠的动物（包括大熊猫）而言，通过监测妊娠哺乳动物通常存在差异的激素谱，无法有效判断其真实妊娠状态。因此，数十年来，科学界始终未能开发出可区分大熊猫妊娠与假妊娠的生理学检测手段。本研究探究了其他潜在的妊娠标志物，发现大熊猫尿液中的急性期蛋白铜蓝蛋白（ceruloplasmin）活性会随妊娠进程升高。结果表明，在足月妊娠个体中，活性尿铜蓝蛋白水平在妊娠首周即显著升高，并持续维持至分娩前20至24天；而在明确的假妊娠周期的黄体期（luteal phase）中，未观察到该蛋白水平的升高。在经超声确认的流产妊娠周期中，尿液活性铜蓝蛋白同样出现升高，但其变化模式与足月妊娠存在差异，尤其在黄体晚期阶段。在本研究纳入的另外5次繁殖周期中，雌性大熊猫均完成配种但未诞下幼崽，其中4次周期的尿液活性铜蓝蛋白在黄体期出现升高。与明确的流产妊娠类似，这些周期中尿液铜蓝蛋白的时间变化模式与足月妊娠存在偏差，提示这些周期大概率也属于流产妊娠。针对圈养大熊猫，学界此前普遍推测其妊娠丢失率较高，而本研究结果首次为这一观点提供了实证支持。