Circulating concentrations of placenta protein 14 during the natural menstrual cycle in women significantly reflect endometrial receptivity to implantation and pregnancy during successive assisted reproduction cycles

Abstract

Placenta protein 14 (PP14), which is the most abundant product of the secretory endometrium, has been proposed as the best biochemical marker of endometrial function in women. In this study, 19 normogonadotrophic women of infertile couples were monitored with serial measurements of concentrations of PP14, gonadotrophins and sex steroids and ultrasound scanning of endometrial thickness throughout three consecutive cycles. The first two of these were natural, unstimulated cycles (cycles 1 and 2), while ovarian stimulation with clomiphene and human menopausal gonadotrophin combined with assisted reproduction (intrauterine insemination in four cases and in-vitro fertilization in 15) was performed in the third cycle (cycle 3). A newly developed enzyme-linked immunosorbent assay was used to measure serum PP14 concentrations. In cycle 3, seven women became pregnant (group A) and 12 did not (group B). Circulating concentrations of PP14 were significantly lower in group A than in group B throughout all three cycles and in all cycle phases with exception of the late luteal phase of cycle 3, during which PP14 concentrations in group A were significantly higher than in group B. Statistical analyses showed no significant correlations between serum concentrations of PP14 and follicle stimulating hormone, luteinizing hormone and progesterone, and endometrial thickness. By contrast, serum oestradiol concentrations during the pre-ovulatory phase were significantly correlated with PP14 concentrations during the mid-luteal phase of the cycle. It is concluded that circulating PP14 is a most reliable biochemical marker of endometrial function in women and that relatively low concentrations in serum during the natural, unstimulated cycle are significantly correlated to implantation and pregnancy during successive assisted reproduction cycles. Measurement of PP14 in serum may thus be useful as a method of screening endometrial function in women, before commencing troublesome and costly treatment for infertility. However, further studies in a much larger number of women are needed to confirm this observation and to elucidate the as yet undefined physiological functions of PP14 in women.

Expression and Localization of Galectin-9 in the Human Uterodome

“…Consistently, they showed that galectin-9 mRNA was expressed at very low concentrations during the proliferative and early secretory phases but showed a sharp and significant increase in the mid-secretory phase [14]. Thus, galectin-9 can be considered as one of the very few epithelial markers, such as glycodelin (PP14) [22], that are strictly regulated during the menstrual cycle. A sharp and strong expression of galectin-9 during the window of implantation suggests a potential role of this lectin during embryo implantation.…”

Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm

“…Available evidence from humans, laboratory animals, and domestic animals indicates that a reduction in uterine histotroph compromises periimplantation conceptus survival and growth, which can lead to infertility and intrauterine growth retardation (9,11,12). Recent studies correlate inadequate expression of cellsurface and secretory proteins with retarded endometrial differentiation and defective endometrial secretory phases (13)(14)(15). Therefore, identification of useful molecular and cellular markers of endometrial function and receptivity to the conceptus are of utmost importance, because they can be used for evaluation, regulation, and enhancement of fertility (15).…”

“…Recent studies correlate inadequate expression of cellsurface and secretory proteins with retarded endometrial differentiation and defective endometrial secretory phases (13)(14)(15). Therefore, identification of useful molecular and cellular markers of endometrial function and receptivity to the conceptus are of utmost importance, because they can be used for evaluation, regulation, and enhancement of fertility (15).…”

Placental Protein 14 Induces Apoptosis in T Cells but Not in Monocytes

“…PP14 also inhibits Natural Killer cell activity (16). That the protein is essential for normal pregnancy progression has been established by the association of low levels of PP14 with habitual abortion (17,18), unexplained infertility (19), and establishment of pregnancy in women during those cycles in which normal concentrations of PP14 were detected (20). Despite the growing literature on the multifunctional role of PP14, the mechanism of action of this protein has not been delineated at the molecular level.…”