Neonatal ovine uterine development involves alterations in expression of receptors for estrogen, progesterone, and prolactin

Effects of age on uterine histoarchitecture, cell proliferation, and hormon e receptor expression were determined for neonatal ewe lambs from birth (Po stnatal Day [PND] 0) to PND 56. Uteri were histologically evaluated and pro liferating 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 bot h. The most striking feature of neonatal uterine development was the genesi s and development of glands in the intercaruncular areas of endometrium. Af ter birth, endometrial glandular epithelium (CE) 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 morphogenesi s of nascent endometrial glands occurred. By PND 56, the uterine wall appea red to be histoarchitecturally mature. At birth, nuclear PCNA protein was s trongly detected in LE. Between PNDs 7 and 56, high levels of PCNA, ER-alph a, and PR gene expression were detected in both nascent and developing GE. Higher levels of PCNA and ER-alpha expression were detected in CE at the ti ps of developing glands as well as in the surrounding stroma. Progesterone was below detectable limits in serum. Serum estradiol-17 beta levels were h igh 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) anal ysis, 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 i n proliferating and differentiating CE. These results indicate that 1) uter ine gland genesis is initiated between PNDs 1 and 7 after birth and is esse ntially completed by PND 56; 2) neonatal uterine morphogenesis involves tem poral and spatial alterations in cell proliferation and ER-alpha, PR, and P RL-R gene expression; 3) PRL-R expression is a unique marker of GE differen tiation and proliferation; and 4) serum estradiol-17 beta and PRL levels in crease during the onset of CE tubular branching morphogenesis. Results supp ort the hypothesis that neonatal ovine uterine development involves epithel ial PRL-R and ER-alpha activation to stimulate and maintain endometrial gla nd genesis and branching morphogenesis.