UMR Physiologie de la Reproduction et des Comportements (INRA, UMR85; CNRS, UMR7247, Université de Tours, IFCE) Nouzilly, France.
Centre de Biophysique Moléculaire (CNRS UPR 4301), France.
PLoS One. 2019 Mar 28;14(3):e0214424. doi: 10.1371/journal.pone.0214424. eCollection 2019.
In temperate regions goat's reproduction is seasonal. To obtain year-round breeding, hormonal treatments are currently applied. These treatments usually combine a progesterone analog with the pregnant mare serum gonadotropin (PMSG). However, their use has significant ethical and environmental drawbacks. Therefore, alternative methods to manage reproduction are needed. The discovery that in mammals the neuropeptide kisspeptin is a major positive regulator of hypothalamo-pituitary gonadal axis offered an attractive alternative strategy to control reproduction. We have previously designed a kisspeptin analog, called C6, which offers pharmacological advantages over endogenous kisspeptin. These include a longer lasting effect and enhanced activity following intramuscular injection. In the present work, we evaluated C6 effect on LH and FSH plasma concentrations in the Alpine goat breed and tested whether C6 could replace PMSG to trigger ovulation. An intramuscular injection of C6 (15 nmol/doe) given 24 hours after the end of progestogen treatment induced a surge-like peak of both LH and FSH. This was followed by an increase of progesterone, a hallmark of ovulation induction and corpus luteus formation. These results were obtained at three different time of the year: during the breeding season, the non-breeding season and at the onset of the breeding season. Furthermore, we compared the efficacy of C6 and PMSG to induce fertile ovulations when these treatments are given at the onset of the breeding season and are followed by artificial insemination. The results of this first attempt were extremely promising with gestation rates of 45% and 64% for C6 and PMSG respectively. Pending optimization of the treatment procedure in order to improve efficacy, kisspeptin analogs could be the long sought-after alternative to PMSG.
在温带地区,山羊的繁殖具有季节性。为了实现全年繁殖,目前正在应用激素处理。这些处理通常将孕激素类似物与孕马血清促性腺激素(PMSG)结合使用。然而,它们的使用存在显著的伦理和环境缺陷。因此,需要寻找替代方法来管理繁殖。发现神经肽 kisspeptin 是调节下丘脑-垂体-性腺轴的主要正调控因子,这为控制繁殖提供了一种有吸引力的替代策略。我们之前设计了一种 kisspeptin 类似物,称为 C6,它在药理学上优于内源性 kisspeptin。这些优势包括肌肉注射后的作用持续时间更长,活性增强。在本研究中,我们评估了 C6 对阿尔卑斯山羊品种 LH 和 FSH 血浆浓度的影响,并测试了 C6 是否可以替代 PMSG 引发排卵。在孕激素处理结束后 24 小时,肌肉注射 C6(15 nmol/只)会引起 LH 和 FSH 的峰类似激增。随后,孕酮增加,这是排卵诱导和黄体形成的标志。这些结果是在一年中的三个不同时间获得的:繁殖季节、非繁殖季节和繁殖季节开始时。此外,我们比较了 C6 和 PMSG 在诱导可育排卵时的效果,当这些处理在繁殖季节开始时进行,并随后进行人工授精时。第一次尝试的结果非常有希望,C6 和 PMSG 的妊娠率分别为 45%和 64%。在优化治疗程序以提高疗效之前,kisspeptin 类似物可能是 PMSG 长期以来的替代品。