Taylor K M, Gray C A, Joyce M M, Stewart M D, Bazer F W, Spencer T E
Center for Animal Biotechnology and Genomics, and Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471, USA.
Biol Reprod. 2000 Oct;63(4):1192-204. doi: 10.1095/biolreprod63.4.1192.
Effects of age on uterine histoarchitecture, cell proliferation, and hormone receptor expression were determined for neonatal ewe lambs from birth (Postnatal Day [PND] 0) to PND 56. Uteri were histologically evaluated and proliferating cell nuclear antigen (PCNA), estrogen receptor alpha (ER-alpha), progesterone receptor (PR), and prolactin receptor (PRL-R) expression were characterized by in situ hybridization (ISH), immunohistochemistry, or both. The most striking feature of neonatal uterine development was the genesis and development of glands in the intercaruncular areas of endometrium. After birth, endometrial glandular epithelium (GE) budded and differentiated into the underlying stroma from the luminal epithelium (LE) between PNDs 1 and 7. Between PNDs 14 and 56, extensive coiling and branching morphogenesis of nascent endometrial glands occurred. By PND 56, the uterine wall appeared to be histoarchitecturally mature. At birth, nuclear PCNA protein was strongly detected in LE. Between PNDs 7 and 56, high levels of PCNA, ER-alpha, and PR gene expression were detected in both nascent and developing GE. Higher levels of PCNA and ER-alpha expression were detected in GE at the tips of developing glands as well as in the surrounding stroma. Progesterone was below detectable limits in serum. Serum estradiol-17beta levels were high on PND 1, increased from PNDs 14 to 28, and declined from PND 42 to PND 56. Serum PRL levels increased from PNDs 1 to 14 and declined thereafter. Using ISH and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, expression of mRNAs for short and long forms of the ovine PRL-R were first detected in nascent GE on PND 7 and increased between PNDs 7 and 56 in proliferating and differentiating GE. These results indicate that 1) uterine gland genesis is initiated between PNDs 1 and 7 after birth and is essentially completed by PND 56; 2) neonatal uterine morphogenesis involves temporal and spatial alterations in cell proliferation and ER-alpha, PR, and PRL-R gene expression; 3) PRL-R expression is a unique marker of GE differentiation and proliferation; and 4) serum estradiol-17beta and PRL levels increase during the onset of GE tubular branching morphogenesis. Results support the hypothesis that neonatal ovine uterine development involves epithelial PRL-R and ER-alpha activation to stimulate and maintain endometrial gland genesis and branching morphogenesis.
研究了从出生（出生后第[PND]0天）到PND 56天的新生母羊羔羊年龄对子宫组织结构、细胞增殖和激素受体表达的影响。对子宫进行组织学评估，并通过原位杂交（ISH）、免疫组织化学或两者结合来表征增殖细胞核抗原（PCNA）、雌激素受体α（ER-α）、孕激素受体（PR）和催乳素受体（PRL-R）的表达。新生子宫发育最显著的特征是子宫内膜肌间区域腺体的发生和发育。出生后，子宫内膜腺上皮（GE）在PND 1至7天之间从腔上皮（LE）向下方基质出芽并分化。在PND 14至56天之间，新生子宫内膜腺体发生广泛的盘绕和分支形态发生。到PND 56天，子宫壁在组织结构上似乎已成熟。出生时，在LE中强烈检测到核PCNA蛋白。在PND 7至56天之间，在新生和发育中的GE中均检测到高水平的PCNA、ER-α和PR基因表达。在发育中腺体尖端的GE以及周围基质中检测到更高水平的PCNA和ER-α表达。血清中孕激素低于可检测限。血清雌二醇-17β水平在PND 1时较高，从PND 14至28天升高，从PND 42至PND 56天下降。血清PRL水平从PND 1至14天升高，此后下降。使用ISH和逆转录聚合酶链反应（RT-PCR）分析，在PND 7天首次在新生GE中检测到绵羊PRL-R短形式和长形式的mRNA表达，并且在PND 7至56天之间在增殖和分化的GE中增加。这些结果表明：1）子宫腺体发生在出生后PND 1至7天之间开始，并在PND 56天基本完成；2）新生子宫形态发生涉及细胞增殖以及ER-α、PR和PRL-R基因表达的时间和空间变化；3）PRL-R表达是GE分化和增殖的独特标志物；4）血清雌二醇-17β和PRL水平在GE管状分支形态发生开始时升高。结果支持以下假设：新生绵羊子宫发育涉及上皮PRL-R和ER-α激活，以刺激和维持子宫内膜腺体发生和分支形态发生。
