Paradoxical effects of kisspeptin: it enhances oocyte in vitro maturation but has an adverse impact on hatched blastocysts during in vitro culture
Paradoxical effects of kisspeptin: it enhances oocyte in vitro maturation but has an adverse impact on hatched blastocysts during in vitro culture
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DOI：
10.1071/rd11118
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发表时间：
2012-01-01
影响因子：
1.9
通讯作者：
Lee, Byeong Chun
中科院分区：
文献类型：
--
作者：
Saadeldin, Islam M.;Koo, Ok Jae;Lee, Byeong Chun
Kisspeptin （Kp）是一种多功能肽，在生殖、心血管系统和癌症中发挥作用。本研究研究了kisspeptin层次因子（KISS1， GNRH1和LHB）及其受体（KISS1R， GNRHR和LHCGR）在猪卵巢和卵母细胞复合物（COCs）中的表达，以及其对卵母细胞体外成熟（IVM）和孤雌电激活后卵母细胞维持着床前胚胎能力的影响。当成熟培养基中添加10(-6)M Kp时，Kp系统元件表达并影响卵母细胞的IVM。与不含Kp的对照组相比，在含Kp的培养基中成熟的卵母细胞成熟度、母细胞基因表达（MOS、GDF9和BMP15）、囊胚形成率、囊胚孵化率和囊胚总细胞数均显著增加。4 × 10(-6) M的Kp拮抗剂（p234）干扰了这一层次结构，但不影响促性腺激素对卵母细胞成熟的阈值效应。FSH通过增加KISS1R的相对表达，对Kp对COCs的作用至关重要。相比之下，Kp显著增加了细胞凋亡，促凋亡基因BAK1的表达，并抑制了培养在饲养细胞上的孵化囊胚的滋养细胞生长。本研究首次提供了猪COCs中Kp层次结构的功能证据，以及它在以自分泌-旁分泌方式促进卵母细胞成熟和随后的发育能力方面的作用。然而，在胚胎发育的关键早期，补充Kp可能会对培养的孵化囊胚产生有害影响，反映出系统或局部的调节。
Kisspeptin (Kp) is best known as a multifunctional peptide with roles in reproduction, the cardiovascular system and cancer. In the present study the expression of kisspeptin hierarchy elements (KISS1, GNRH1 and LHB) and their receptors (KISS1R, GNRHR and LHCGR, respectively) in porcine ovary and in cumulus-oocyte complexes (COCs) were investigated, as were its effects on the in vitro maturation (IVM) of oocytes and their subsequent ability to sustain preimplantation embryo competence after parthenogenetic electrical activation. Kp system elements were expressed and affected IVM of oocytes when maturation medium was supplemented with 10(-6) M Kp. Oocyte maturation, maternal gene expression (MOS, GDF9 and BMP15), blastocyst formation rate, blastocyst hatching and blastocyst total cell count were all significantly increased when oocytes were matured in medium containing Kp compared with the control group (without Kp). A Kp antagonist (p234) at 4 x 10(-6) M interfered with this hierarchy but did not influence the threshold effect of gonadotrophins on oocyte maturation. FSH was critical and permissive to Kp action on COCs by increasing the relative expression of KISS1R. In contrast, Kp significantly increased apoptosis, the expression of pro-apoptotic gene, BAK1, and suppressed trophoblast outgrowths from hatched blastocysts cultured on feeder cells. The present study provides the first functional evidence of the Kp hierarchy in porcine COCs and its role in enhancing oocyte maturation and subsequent developmental competence in an autocrine-paracrine manner. However, Kp supplementation may have a harmful impact on cultured hatched blastocysts reflecting systemic or local regulation during the critical early period of embryonic development.