Department of Pathology and Laboratory Medicine, USA.
Department of Molecular and Integrative Physiology, USA.
Mol Cell Endocrinol. 2021 May 1;527:111208. doi: 10.1016/j.mce.2021.111208. Epub 2021 Feb 13.
Kisspeptin (KISS1) signaling in the hypothalamic-pituitary (H-P) axis plays an essential role in regulating gonadotropin secretion. KISS1 and KISS1 receptor (KISS1R) are also expressed in the ovary; however, the role of intraovarian KISS1 signaling remains unclear. Granulosa cell (GC)-specific expression of KISS1, and oocyte-specific expression of KISS1R indicate that GC-derived KISS1 may act on oocytes. Expression of KISS1 in GCs is induced by gonadotropins but it is absent in estrogen receptor β knockout (Erβ) rat ovaries. We also observed that gonadotropin stimulation failed to induce maturation of Erβ oocytes. Interestingly, KISS1 treatment of cumulus oocyte complexes (COCs) isolated from antral follicles promotes in vitro maturation of oocytes. Treatment of oocytes with KISS1 induced intracellular Ca release, and increased activation of MAP kinase ERK1/2. KISS1 treatment also induced the expression of oocyte genes that are crucial for differentiation of GCs, and maturation of oocytes. Our findings suggest that ovarian KISS1-signaling plays an important role in gonadotropin induced follicle development and oocyte maturation.
下丘脑-垂体(H-P)轴中的 Kisspeptin(KISS1)信号在调节促性腺激素分泌中起着至关重要的作用。KISS1 和 KISS1 受体(KISS1R)也在卵巢中表达;然而,卵巢内 KISS1 信号的作用尚不清楚。颗粒细胞(GC)特异性表达 KISS1 和卵母细胞特异性表达 KISS1R 表明 GC 来源的 KISS1 可能作用于卵母细胞。GC 中 KISS1 的表达受促性腺激素诱导,但在雌激素受体β敲除(Erβ)大鼠卵巢中不存在。我们还观察到,促性腺激素刺激未能诱导 Erβ卵母细胞成熟。有趣的是,来自窦卵泡的卵丘卵母细胞复合物(COC)中 KISS1 的处理促进卵母细胞的体外成熟。KISS1 处理诱导卵母细胞内 Ca 释放,并增加 MAP 激酶 ERK1/2 的激活。KISS1 处理还诱导了对 GC 分化和卵母细胞成熟至关重要的卵母细胞基因的表达。我们的研究结果表明,卵巢 KISS1 信号在促性腺激素诱导的卵泡发育和卵母细胞成熟中起着重要作用。