Detection of the nucleolar channel system of human endometrium and uses thereof
View Patent ↗Methods are disclosed for assaying at the light microscopic level for the presence or absence of nucleolar channel systems (NCSs) in an endometrial tissue sample, as are methods for determining whether or not a postovulatory human endometrium is in a state that is receptive for implantation of a human embryo, where the presence of NCSs indicates that the endometrium is in a state that is receptive for implantation of an embryo and the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of the embryo, and methods for determining the effectiveness of a contraceptive in a woman, comprising assaying an endometrial tissue sample for the presence or absence of NCSs.
1. A method of assaying for the presence or absence of nucleolar channel systems (NCSs) in an endometrial tissue sample, where the method comprises contacting the tissue sample with an agent that is specific for a protein selected from the group consisting of Nup153, Nup62, Lamin A/C, Lamin A, Lamin B2, Emerin, Calnexin, Binding immunoglobulin Protein (BiP), Protein disulfide isomerase (PDI), and CLIMP63, wherein the agent is an antibody or an antibody fragment, and wherein the presence of the protein within nuclei of endometrial epithelial cells indicates the presence of NCSs in the endometrial tissue sample and wherein the absence of the protein within nuclei of endometrial epithelial cells indicates the absence of NCSs in the endometrial tissue sample.
2. The method of claim 1 , wherein the agent binds to Nup153, Lamin A/C or Emerin.
3. The method of claim 1 , wherein the presence of NCSs indicates that the endometrium is in a state that is receptive for implantation of an embryo.
4. The method of claim 1 , wherein the tissue sample is obtained from the endometrium of a woman between day 18 and day 24 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
5. The method of claim 1 , wherein the tissue sample is obtained from the endometrium of a woman between day 19 and day 22 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
6. The method of claim 1 , wherein the tissue sample is obtained from the endometrium of a woman between day 4 and day 9 of the luteal phase of the menstrual cycle, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
7. The method of claim 1 , wherein the tissue sample is obtained from the endometrium of a woman between day 5 and day 8 of the luteal phase of the menstrual cycle, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
8. The method of claim 1 , wherein the presence or absence of the protein is determined using a light microscope.
9. A method of determining whether or not a postovulatory human endometrium is in a state that is receptive for implantation of a human embryo, the method comprising contacting a tissue sample from the endometrium with an agent that binds to nucleolar channel systems (NCSs), wherein the presence of NCSs indicates that the endometrium is in a state that is receptive for implantation of an embryo and the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo, wherein the agent that binds to NCSs is an antibody or an antibody fragment and wherein the agent binds to Nup153, Nup62, Lamin A/C, Lamin A, Lamin B2, Emerin, Calnexin, Binding immunoglobulin Protein (BiP), Protein disulfide isomerase (PDI) or CLIMP63within the nuclei of endometrial epithelial cells from the tissue sample.
10. The method of claim 9 , wherein the tissue sample is obtained from the endometrium of a woman between day 18 and day 24 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss.
11. The method of claim 9 , wherein the tissue sample is obtained from the endometrium of a woman between day 19 and day 22 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss.
12. The method of claim 9 , wherein the agent binds to Nup153, Lamin A/C or Emerin.
13. The method of claim 9 , wherein the presence of NCSs is detected between day 18 and day 24 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss.
14. The method of claim 9 , wherein the presence of NCSs is detected between day 19 and day 22 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss.
15. The method of claim 9 , wherein the presence of NCSs is detected between day 4 and day 9 of the luteal phase of the menstrual cycle.
16. The method of claim 9 , wherein the presence of NCSs is detected between day 5 and day 8 of the luteal phase of the menstrual cycle.