Prolactin-like protein-f subfamily of placental hormones/cytokines: responsiveness to maternal hypoxia.

The prolactin (PRL) family of hormones/cytokines is involved in the maintenance of pregnancy and adaptations to physiological stressors. In this report, we identify and characterize a new member of the rat PRL family, examine the impact of maternal hypoxia on placental PRL family gene expression, and investigate maternal adaptive responses to hypoxia. Perusal of the PRL gene family locus in the rat genome resulted in the identification of a putative new member of the rat PRL family. The new member is closely related to the previously reported PRL-like protein-F (PLP-F) and has been named PLP-Fbeta and the originally characterized PLP-F, now termed PLP-Falpha. The two proteins exhibit structural similarities but possess distinct cell- and temporal-specific expression profiles. In vivo hypoxia stimulates placental PLP-Falpha and PLP-E mRNA expression in the rat and mouse, respectively. Rcho-1 trophoblast cells can differentiate into trophoblast giant cells, express PLP-Falpha, and exhibit enhanced PLP-Falpha mRNA levels when cultured under low oxygen tension (2%). Exposure to hypobaric hypoxia during latter part of pregnancy did not significantly impact the expression of PLP-Fbeta mRNA. Finally, exposure to hypobaric hypoxia during midpregnancy led to increased maternal red blood cells, hemoglobin concentrations, hematocrit, and increased concentrations of maternal splenic mRNAs for key proteins involved in hemoglobin synthesis, erythroid Krüppel-like factor, erythroid 5-aminolevulinate synthase-2, and beta-major globin. In summary, adaptive responses to maternal hypoxia include activation of placental PLP-Falpha/E gene expression, which may then participate in maternal hematological adjustments required for maintaining maternal and fetal oxygen delivery.

Hypobaric hypoxia as a tool to study pregnancy-dependent responses at the maternal-fetal interface.

Establishment of proper oxygen and nutrient supply to the fetus is essential for a successful pregnancy. The maternal-fetal interface is the site of vascular modifications, providing a conduit for the delivery of essential nutrients to the developing fetus. Pregnancy-dependent adaptive vascular responses within the uteroplacental compartment can be exaggerated by exposure to a physiological stressor such as hypoxia. A simple procedure for exposing pregnant rats and mice to hypobaric hypoxia is presented.

Subfertility linked to combined luteal insufficiency and uterine progesterone resistance.

Early pregnancy loss is common and can be caused by a range of factors. The Brown Norway (BN) rat exhibits reproductive dysfunction characterized by small litter size and pregnancy failure and represents a model for investigating early pregnancy loss. In this study, we investigated the establishment of pregnancy in the BN rat and gained insight into mechanisms causing its subfertility. Early stages of BN uteroplacental organization are unique. The BN primordial placenta is restricted in its development and correlates with limited BN uterine decidual development. BN uterine decidua was shown to be both structurally and functionally distinct and correlated with decreased circulating progesterone (P4) levels. Ovarian anomalies were also apparent in BN rats and included decreased ovulation rates and decreased transcript levels for some steroidogenic enzymes. Attempts to rescue the BN uterine decidual phenotype with steroid hormone therapy were ineffective. BN uteri were shown to exhibit reduced responsiveness to P4 but not to 17beta-estradiol. P4 resistance was associated with decreased transcript levels for the P4 receptor (Pgr), a P4 receptor chaperone (Fkbp4), and P4 receptor coactivators (Ncoa1 and Ncoa2). In summary, the BN rat exhibits luteal insufficiency and uterine P4 resistance, which profoundly affects its ability to reproduce.

The rat prolactin gene family locus: species-specific gene family expansion.

In the rat there is a large family of paralogous genes related to prolactin (PRL). Members of the PRL family are expressed in cell- and temporal-specific patterns in the anterior pituitary, uterus, and placenta. An overriding feature of the PRL family is its association with pregnancy. In this investigation, we used information derived from the public rat genome database as a tool for identifying new members of the rat PRL family. The entire rat PRL gene family locus spans approximately 1.7 megabases (Mb) on Chromosome 17. Genes possessed either 5- or 6-exon organization patterns. We provide information on three newly identified genes orthologous to previously identified members of the mouse PRL gene family [placental lactogen-Ialpha (PL-Ialpha), PL-Ibeta, and proliferin (PLF)] and a new member of the PRL family, termed PRL-like protein-P (PLP-P). Information is also presented on the existence of multiple PLP-M transcripts, which are generated by alternative splicing. Expansion of the PRL family has occurred independently in rodents versus the cow and does not exist in the human and dog. Elucidation of the rat PRL gene family locus provides tools for studying the genetics and biology of the rat PRL family and new insights into species-specific gene family expansion.