Abstract
Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.
Highlights
Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation
In day of pseudopregnancy 4 (DOPP 4) wildtype (WT) mice, immunoreactive Forkhead box A2 (FOXA2) protein was detected in the nuclei of glandular epithelia (GE) cells in the endometrium and was not present in other uterine cell types (LE, stroma or myometrium) (Fig. 1)
Both WT and progesterone-induced uterine gland knockout (PUGKO) mice were mated to intact males, and blastocysts were recovered from the uterine lumen on gestational day (GD) 4
Summary
Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. Many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy. Uterine function is primarily regulated by the ovarian steroid hormones estrogen and progesterone[11] Under their influence, the LE, glandular epithelia (GE), and stroma express genes important for uterine receptivity and blastocyst implantation, including cytokines, growth factors, and lipid mediators[2,12,13,14]. How uterine glands regulate those fundamental processes important for the establishment and maintenance of pregnancy is not well understood
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