以生殖控制進行台灣獼猴族群管理之適用性-保育醫學之實踐

Evaluation of reproduction control as a method of population management in Formosan macaque (Macaca cyclopis) - Conservation Medicine in Practice

余品奐(Pin-Huan Yu)

指導教授 ： 季昭華

國立臺灣大學/獸醫專業學院/獸醫學研究所/博士(2015年)

https://doi.org/10.6342/NTU.2015.02486

摘要

台灣獼猴(Macaca cyclopis)為台灣特有種，近來隨著棲地開發及族群擴張，其與人類生活空間重疊情形日增，並衍生許多衝突。這之間包含了野生動物生態學、生物學、公共衛生、人畜共同傳染病、獸醫學等範疇，此一問題事實上是一牽涉人類、動物、生態健康的保育醫學議題，需不同領域的專業人士共同合作方能有效、全面且平衡的解決問題。本研究將從獸醫學及保育醫學的觀點切入，並與保育生物學、野生動物學、生態學專家共同合作，研究不同生殖控制方法對於台灣獼猴族群管理之適用性以及探討保育醫學如何在這樣的實際案例中落實。
台灣獼猴是在獼猴屬下十九個種中被認識的最少的品種之一，雖然針對其他獼猴之卵巢週期及生殖荷爾蒙已進行了相當透徹的研究，但對於台灣獼猴生殖荷爾蒙所知仍有限。因此，本研究的第一個部份目的是了解台灣獼猴之生殖生理以及卵巢週期中卵巢及性荷爾蒙的變化。自2013年二月至2013年十一月，11隻雌性成年台灣獼猴選入此研究，獼猴於月經的第一天，以及其後的第4、 7、 10、 11、 12、 13、 14、 15、 16、 18、 20、 22、 24、27日在麻醉下進行採血並針對雌二醇及孕酮濃度分析。在月經的第一天及其後的每六天進行一次內視鏡觀察，但在排卵期則每天進行。卵巢週期，濾泡期及黃體期的長度分別為29.2 ± 1.3天、13.3 ± 2.1天及14.1 ± 1.3天，同時我們比較血清中荷爾蒙濃度變化與內視鏡觀察之發現：雌二醇濃度的高峰為290 ± 12.7 pg/ml，並可預測排卵將在其後的24-48小時內發生；孕酮在排卵後8天上升至最高值9.13 ± 1.78 ng/ml，接著逐漸下降。此資料可做為台灣獼猴性荷爾蒙之參考值，並對未來的研究有所裨益。
第二部份的研究目的以簡單實用與非侵入性的操作方式控制臺灣獼猴的動情週期，期望可以達到臺灣獼猴之生殖抑制。試驗進行前獼猴先依血漿中孕酮(progesterone)與雌二醇(estradiol)濃度、陰道抹片及性皮腫脹確定有正常之動情週期。隨後將14隻成熟雌性之臺灣獼猴分為三組：第一組以肌肉注射方式給予醋酸甲羥孕酮(medroxyprogesterone acetate)第二組以口服方式投予左炔諾孕酮(levonorgestrel);第三組為對照組。觀察雌性獼猴之動情週期平均為28.29 ± 5.3天，陰道細胞學與排卵週期具有週期性變化，但性皮腫脹程度及增紅程度並不明顯;試驗結果發現：第一組獼猴使用醋酸甲羥孕酮注射後，其血漿中雌二醇及孕酮濃度均顯著受到抑制，三個月平均分別為23.07±4.99 pg/ml及 0.47±0.15 ng/ml，顯著低於對照組正常動情週期之性荷蒙濃度，顯示試驗獼猴之發情週期受到抑制。第二組獼猴使用左炔諾孕酮口服投予兩次後，僅一個體出現延遲排卵現象，此時雌二醇及孕酮之平均濃度分別為30.58±7.62 pg/ml及0.22±0.02 ng/ml ，顯著低於對照組。估計之排卵時間離最後一次投藥後約59天。由試驗可知臺灣獼猴以肌肉注射醋酸甲羥孕酮可成功延長成熟雌猴之動情週期與排卵至少三個月，而左炔諾孕酮之效力受受試個體投藥時之生殖週期影響，因此醋酸甲羥孕酮較適合做為野外獼猴非侵入性生育控制之方法。
第三部份為內視鏡輸卵管結紮做為台灣獼猴生殖控制之安全性評估及術後追蹤。研究中19隻成年雌性台灣獼猴在麻醉下其輸卵管以2.7毫米內視鏡系統進行電燒及截斷。我們記錄術中之併發症，並以客觀的方法對術中出血進行評分。術後監控兩個週期的血清性荷爾蒙趨勢以確定卵巢功能。在術後的2至13個月，19隻獼猴中的8隻則再次進行內視鏡觀察；並客觀地針對輸卵管及生殖系統的發炎狀態進行評分。實驗中沒有記錄到任何嚴重的麻醉及手術併發症。荷爾蒙分析則顯示術後仍有正常的卵巢週期，且其模式仍與參考值相仿。術後生殖系統的發炎反應為有限到低度的，並且低於其他在獼猴使用之輸卵管阻斷方法。因此利用2.7毫米硬鏡系統於台灣獼猴之輸卵管結紮是安全且有效率的方法，且相較於其他已知的節育技巧造成更少的術後併發症。
總計此研究共與13個公私立單位進行合作，其中包含三所學術單位不同領域的專家，進行圈養及野生台灣獼猴之節育及野放追蹤，落實保育醫學中一個地球、一體健康的概念。節育效果則以肌肉注射醋酸甲羥孕酮及內視鏡輸卵管結紮為首選，但野外工作需考慮季節、棲地、動物等因素，仍有待更多經驗讓工作流程更有效率。綜合本研究結果，透過建立台灣獼猴性荷爾蒙之基礎值，我們評估對於台灣獼猴最適合的節育方法，內視鏡輸卵管結紮提供安全、永久且有效的節育方法，長期來說，在野生動物的族群管理上是較為實際且有效率的選擇。

關鍵字

台灣獼猴 ； 保育醫學 ； 生育控制 ； 內視鏡 ； 荷爾蒙 ； 生殖週期

並列摘要

The Formosan macaque (Macaca cyclopis) is a primate native to Taiwan
As in other countries, conflicts between humans and macaques in Taiwan are a public health concern. This issue also covers other subjects like wildlife ecology, biology, zoonotic disease and veterinary medicine which involve the health of human, animal and ecosystem as a conservation medicine topic. Professionals from different area are needed to solve this problem thoroughly, effectively and balance. This study will starts from the aspect of veterinary medicine and conservation medicine and cooperate with professionals from biology, zoology and ecology, to investigate the applicability of different strategy in Formosan macaque and how does the spirit of conservation medicine conduct in this case.
The Formosan macaque is considered one of the least known among the 19 extant species of the genus Macaca. Although studies of reproductive hormones and the ovarian cycle have been extensively conducted on other macaques, there is little information of Formosan macaques. The purpose of the first part of present study was to establish information about the reproductive physiology of Formosan macaques. From February 2013 to November 2013, 11 wild adult female Formosan macaques were selected for the study. Blood sampling from anesthetized macaques started on the day of first menstrual bleeding and was performed on days 4, 7, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, and 27 afterwards. Laparoscopic examination was carried out every six days after the first day of menstrual bleeding, and daily during the periovulatory stage. The duration of the ovarian cycle, follicular phase and luteal phase was 29.2 ± 1.3 days, 13.3 ± 2.1 days and 14.1 ± 1.3 days respectively. In addition, changes in serum levels of sex hormones were coMPAred with endoscopic observations; the peak serum level of estradiol was 290 ± 12.7 pg/ml, and predicted an ovulation episode within 24–48 hours. Serum progesterone rose to a peak of 9.13 ± 1.78 ng/ml eight days after ovulation and then declined gradually. The data may be considered as reference values associated with the ovarian cycle in Formosan macaques. Hopefully, the study will be beneficial to further studies and the conservation of this endemic species in Taiwan.
In the second part of present study, we evaluate noninvasive methods of reproductive control in Formosan macaque. All macaques in the study were tested for the cyclicity of serum level of progesterone and estradiol, vaginal smear and the swollen of perineal sex-skin to make sure all females are in normal ovarian cycle. 14 female adult Formosan macaques were divided into three groups: group one was injected with medroxyprogesterone acetate intramuscularly, group two was given levonorgestrel orally and group three was control group. The duration of ovarian cycle was 28.29 ± 5.3 days, there was cyclicity in vaginal smear and sex hormones. But the change in perineal sex skin was not prominent. Our study shows that after using MPA in Formosa macaque, serum estradiol and progesterone level were prominently suppressed, the average serum concentration of estradiol and progesterone were 23.07±4.99 pg/ml and 0.47±0.15 ng/ml respectively during the three months suppression. In the LNG group, only one individual demonstrated delay in ovulation. The average serum estradiol and progesterone concentration was 30.58±7.62 pg/ml and 0.22±0.02 ng/ml respectively during this period, which was prominently lower than control group. The estimated ovulation time was 59 days later than last day of medication. This study demonstrates that MPA intramuscular injection could successfully suppress estrus cycle for at least three months, and the efficacy of LNG is affected by the stage of ovarian cycle upon the time of dosing. Therefore, MPA is a more suitable choice for medical population control in Macaca Cyclopis in the field.
In the third part of the study, we evaluated the safety and postsurgical outcomes of endoscopic salpingectomy for sterilization of female Formosan macaques (Macaca cyclopis) as a method of population control. Nineteen adult female Formosan macaques were included in our study. The fallopian tubes of each anesthetized macaque were cauterized and excised endoscopically using a 2.7-mm rigid endoscope system. We recorded the complications encountered, and objectively scored the amount of hemorrhage throughout the procedure. Postoperative ovarian function was evaluated by monitoring the serum levels of sex hormones in ten of the macaques for two ovarian cycles following the salpingectomy. Two to 13 months later, eight of the 19 macaques underwent laparoscopy for the objective evaluation of inflammation at the surgical sites on the fallopian tubes. No major anesthetic- or surgical-associated complications were observed in any of the macaques. The hormonal evaluation showed cyclic ovarian function after salpingectomy in all of the ten macaques examined, and the parameters were coMPArable to those of other macaque species. The long-term postoperative level of inflammation at the surgical site was minimal to low, and was lower than that reported for other tubal occlusion techniques used in macaques. The use of a 2.7-mm rigid endoscope for salpingectomy in macaques is safe and efficient, with fewer postoperative complications than coMPArable sterilization techniques.
In this study, we cooperate with thirteen different public or private facilities which include three academic facilities. Together we conducted contraception in captive and wild macaque, release to the wild and follow up. Fulfill the concept one planet, one healthy of conservation medicine. The outcome of contraception is better with the usage of medroxyprogesterone acetae and endoscopic salpingectomy. However, multiple factors such as season, habitat and animals should be considered in field work, more experience is expected to fluent the protocol. In conclusion, hormone study is fundamental to many researches, we evaluate the suitableness of different contraceptive methods through the establishment of sex hormones of Formosan macaques. Endoscopic salpingectomy provides safe, effective and permanent contraceptive method. It is a more practical and efficient approach in the wild animal management.

並列關鍵字

Formosan macaque (Macaca cyclopis) ； conservation medicine ； reproduction control ； endoscopic salpingectomy ； hormone ； ovarian cycle

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