Department of Anatomy, Physiology and Pharmacology, Cellular and Molecular Biosciences Program, Auburn University, Auburn, AL 36849, USA.
Biol Reprod. 2013 Jan 3;88(1):4. doi: 10.1095/biolreprod.112.105056. Print 2013 Jan.
The first 2 wk of neonatal life constitute a critical period for estrogen receptor alpha (ESR1)-dependent uterine adenogenesis in the pig. A relaxin receptor (RXFP1)-mediated, lactocrine-driven mechanism was proposed to explain how nursing could regulate endometrial ESR1 and related gene expression events associated with adenogenesis in the porcine neonate during this period. To determine effects of nursing on endometrial morphogenesis and cell compartment-specific gene expression, gilts (n = 6-8/group) were assigned at birth to be either 1) nursed ad libitum for 48 h, 2) gavage fed milk replacer for 48 h, 3) nursed ad libitum to Postnatal Day (PND) 14, or 4) gavage fed milk replacer for 48 h followed by ad libitum nursing to PND 14. Uteri were collected on PND 2 or PND 14. Endometrial histoarchitecture and both ESR1 and proliferating cell nuclear antigen (PCNA) labeling indexes (LIs) were evaluated. Laser microdissection was used to capture epithelium and stroma to evaluate treatment effects on cell compartment-specific ESR1, VEGFA, and RXFP1 expression. Imposition of a lactocrine-null state by milk replacer feeding for 48 h from birth retarded endometrial development and adenogenesis. Effects of replacer feeding, evident by PND 2, were marked by PND 14 when endometrial thickness, glandularity, and gland depth were reduced. Consistently, in lactocrine-null gilts, PCNA LI was reduced in glandular epithelium (GE) and stroma on PND 14, when epithelial ESR1 expression and ESR1 LI in GE were reduced and stromal VEGFA and RXFP1 expression increased. Results establish that lactocrine signaling effects morphogenetic changes in developing uterine tissues that may determine reproductive capacity later in life.
新生后两周是猪子宫腺发生的关键时期，在此期间雌激素受体 α（ESR1）依赖。提出了一种松弛素受体（RXFP1）介导的乳分泌驱动机制，以解释哺乳期如何调节新生猪子宫内膜 ESR1 及其相关基因表达事件，从而促进腺发生。为了确定哺乳对子宫内膜形态发生和细胞区室特异性基因表达的影响，分娩后的小母猪（每组 6-8 只）被分配到以下 4 个组：1）自由哺乳 48 小时，2）用代乳料灌胃 48 小时，3）自由哺乳至出生后第 14 天，4）用代乳料灌胃 48 小时，然后自由哺乳至出生后第 14 天。在出生后第 2 天或第 14 天采集子宫。评估子宫内膜组织学结构以及 ESR1 和增殖细胞核抗原（PCNA）标记指数（LI）。激光显微切割用于捕获上皮和基质，以评估处理对细胞区室特异性 ESR1、VEGFA 和 RXFP1 表达的影响。从出生开始用代乳料灌胃 48 小时会导致子宫发育和腺发生延迟。代乳料喂养的影响在出生后第 2 天即可观察到，并在第 14 天变得明显，此时子宫内膜厚度、腺状和腺深度降低。一致地，在乳分泌缺失的小母猪中，PCNA LI 在第 14 天的腺上皮（GE）和基质中降低，此时上皮 ESR1 表达和 GE 中的 ESR1 LI 降低，而基质中的 VEGFA 和 RXFP1 表达增加。结果表明，乳分泌信号影响发育中子宫组织的形态发生变化，这些变化可能决定以后的生殖能力。
