Ede Marie Apostolakis

Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform

Withdrawal of progestational support for pregnancy is part of the final common pathways for parturition, but the role of nuclear progesterone receptor (PGR) isoforms in this process is not known. To determine if the PGR-B isoform participates in cervical remodeling at term, cervices were obtained from mice lacking PGR-B (PGR-BKO) and from wild-type (WT) controls before or after birth. PGR-BKO mice gave birth to viable pups at the same time as WT controls during the early morning of Day 19 postbreeding. Morphological analyses indicated that by the day before birth, cervices from PGR-BKO and WT mice had increased in size, with fewer cell nuclei/area as well as diminished collagen content and structure, as evidenced by optical density of picrosirius red-stained sections, compared to cervices from nonpregnant mice. Moreover, increased numbers of resident macrophages, but not neutrophils, were found in the prepartum cervix of PGR-BKO compared to nonpregnant mice, parallel to findings in WT mice. These results suggest that PGR-B does not contribute to the growth or degradation of the extracellular matrix or proinflammatory processes associated with recruitment of macrophages in the cervix leading up to birth. Rather, other receptors may contribute to the progesterone-dependent mechanism that promotes remodeling of the cervix during pregnancy and in the proinflammatory process associated with ripening before parturition. A progesterone-mediated receptor mechanism that does not involve the progesterone receptor-B isoform maintains pregnancy and regulates cervical remodeling and parturition.

Hormonal regulation of hypothalamic gene expression: Identification of multiple novel estrogen induced genes

Estrogen (E) has been shown to play a major role in hypothalamic function and is a prerequisite for progesterone (P) induced sexual behavior in female rats. In the course of studies in search of steroid induced hypothalamic genes, we discovered a surprisingly large number of E-induced genes (21 mRNAs in total). This is the largest number of E-induced genes ever identified in a single organ. Many of these mRNAs exhibit considerable magnitudes of induction and their levels were maintained typically during subsequent P treatment. Among the induced genes, several encode metabolic enzymes and may account for some of the morphological changes observed in hypothalamic neurons in response to E. Since E appears to play a major role in defining the pattern of hypothalamic gene expression in conjunction with its capacity for behavioral modulation, these newly identified cDNAs may serve as genetic markers for correlative studies of E-induced central nervous system behavior.

12 – Pulsatile Endocrine Secretion in the Ovine Fetus

Publisher Summary The ontogenesis of neuroendocrine function and the physiological role of the hypothalamic-pituitary axis in the fetus are critical issues for understanding growth and development of the fetus in utero. Access to the fetus and its circulation requires technological expertise and extensive surgical skills to ensure the long-term viability of the experimental model. The preparation for fetal surgery is critical to its success because the health and well-being of the fetus is an absolute prerequisite for experimentation. Proper training in the techniques of sterile surgery is essential for all involved with the project. Catheters are placed first in the pregnant ewe to obtain an arterial blood-gas measurement and assess animal well-being. An opening to expose the uterus is initially made with a superficial incision near midline and then into the abdominal cavity along the linea alba. Palpation within the peritoneal cavity is necessary to determine the number of fetuses and their orientation. The fetal forelimb is identified by its flexion and manipulated to an avascular portion of the uterine horn.