Preimplantation Endometrial Transcriptomics in Natural Conception Cycle of the Rhesus Monkey

Muzaffer Bhat,P.G.L Lalitkumar,Jayasree Sengupta,Jeevitha Poorasamy,Meraj Khan,Debabrata Ghosh

doi:10.3390/reprodmed3010003

Abstract

There is no report on preimplantation phase endometrial transcriptomics in natural conception cycles of primates. In the present study, the whole-genome expression array of endometrium on Days 2, 4, and 6 post-ovulation (pov) in proven natural conception (Group 1; n = 12) and non-mated, ovulatory (Group 2; n = 12) cycles of rhesus monkeys was examined, compared, and validated. Of fifteen (15) genes showing differential expression (>2-fold; pFDR < 0.05), six genes (CHRND, FOXD3, GJD4, MAPK8IP3, MKS1, and NUP50) were upregulated, while eight genes (ADCY5, ADIPOR1, NNMT, PATL1, PIGV, TGFBR2, TOX2, and VWA5B1) were down regulated on Day 6 pov as compared to Day 2 pov in conception cycles. On Day 6 pov, four genes (ADCY5, NNMT, TOX2, and VWA5B1) were down regulated, and AVEN was upregulated in conception cycles compared with the non-conception cycle. These observations were orthogonally validated at protein expression level. Group-specifically expressed unique genes in conception cycles influence the process of induction of immune-tolerance, while the genes expressed in both groups influence processes of protein targeting and metabolism. A triad of timed-actions of progesterone, seminal plasma, and preimplantation embryo putatively regulate several input molecules to CREB, NF-kB, and STAT regulatory networks during secretory phase towards evolution of endometrial receptivity in the rhesus monkey.

Highlights

The biology of endometrium during embryo implantation in the human is a ‘black box’ [1,2]
We have examined the whole-genome expression of preimplantation stage endometrium in natural conception cycle and compared the former with the secretory phase of normo-ovulatory non-mated cycles of proven fertile rhesus monkeys and observed that functional networks involving CREB, NF-kB, and STAT regulatory modules in implantation stage endometrium may be operative in natural conception cycle
Tissue samples obtained from 16 animals in this group categorized in the non-fecund cycle group (Group 2) were used for total RNA extraction followed by their quality and quantity assessments, and four samples could not be used since their RIN scores were less than 8.0

Summary

Introduction

The biology of endometrium during embryo implantation in the human is a ‘black box’ [1,2]. Licht et al (1998) employed an interesting model to investigate the nature of endometrial responses following intrauterine infusion of putative embryonic factors in the secretory phase of cycle [5]. These studies revealed many interesting facets of implantation biology, the complete absence of a dynamic relationship between a developing preimplantation stage embryo and the primed endometrium as it attains its receptive status for nidation was a major limitation in these experimental approaches [2,6,7]

Methods

Results

Discussion

Conclusion