Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: Amino acid transport

Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: Amino acid transport
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DOI:
10.1095/biolreprod.105.041798
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发表时间:
2005-08-01
影响因子:
3.6
通讯作者:
Pendola, JK
Pendola, JK
中科院分区:
生物学2区
文献类型:
--
作者:
Eppig, JJ;Pendola, FL;Pendola, JK

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寻找基因表达更高的小鼠卵丘细胞比壁颗粒细胞差减杂交产生S1 c38 a3。SLC 38 A3是一种钠偶联中性氨基酸转运蛋白,对L-谷氨酸、L-组氨酸和L-丙氨酸具有底物偏好性。通过原位杂交在大腔前卵泡的颗粒细胞中发现了可检测水平的S1 c38 a3 mRNA,但在小腔卵泡的所有颗粒细胞中水平较高;表达仅限于大腔卵泡的卵丘细胞。S1 c38 a3 mRNA在颗粒细胞中的表达被完全生长的窦状卵泡卵母细胞所促进,但不被生长的窦前卵泡卵母细胞所促进。完全发育的卵母细胞依赖于卵丘细胞摄取L-丙氨酸和L-组氨酸,而不摄取L-亮氨酸。完全生长但不生长的卵母细胞分泌一种或多种旁分泌因子,促进卵丘细胞摄取所有三种氨基酸,但L-丙氨酸和L-组氨酸的程度远大于L-亮氨酸。L-亮氨酸的摄取似乎主要依赖于来自完全生长的卵母细胞的接触介导的信号。完全生长的卵母细胞也促进窦前颗粒细胞S1 c38 a3 mRNA和L-丙氨酸转运水平升高,但生长的卵母细胞没有。因此,完全生长的卵母细胞分泌一种或多种旁分泌因子,促进卵丘细胞摄取卵母细胞本身转运较差的氨基酸。这些氨基酸可能通过间隙连接转移到卵母细胞。因此,卵母细胞利用旁分泌信号通过与卵丘细胞的代谢协同作用促进自身发育。卵母细胞介导这种协同性的能力是发育调节的,并且仅在卵母细胞发育的后期获得。
A search for genes expressed more highly in mouse cumulus cells than mural granulosa cells by subtraction hybridization yielded S1c38a3. SLC38A3 is a sodium-coupled neutral amino acid transporter having substrate preference for L-glutamate, L-histidine, and L-alanine. Detectable levels of S1c38a3 mRNA were found by in situ hybridization in granulosa cells of large preantral follicles, but levels were higher in all granulosa cells of small antral follicles; expression became limited to cumulus cells of large antral follicles. Expression of S1c38a3 mRNA in granulosa cells was promoted by fully grown oocytes from antral follicles but not by growing oocytes from preantral follicles. Fully grown oocytes were dependent on cumulus cells for uptake Of L-alanine and L-histidine but not L-leucine. Fully grown but not growing oocytes secreted one or more paracrine factors that promoted cumulus cell uptake of all three amino acids but Of L-alanine and L-histidine to a much greater extent than L-leucine. Uptake Of L-leucine appeared dependent primarily on contact-mediated signals from fully grown oocytes. Fully grown oocytes also promoted elevated levels of S1c38a3 mRNA and L-alanine transport by preantral granulosa cells, but growing oocytes did not. Therefore, fully grown oocytes secrete one or more paracrine factors that promote cumulus cell uptake of amino acids that oocytes themselves transport poorly. These amino acids are likely transferred to oocytes via gap junctions. Thus, oocytes use paracrine signals to promote their own development via metabolic cooperativity with cumulus cells. The ability of oocytes to mediate this cooperativity is developmentally regulated and acquired only in later stages of oocyte development.