The eutherian species evolved an elaborate uterus to allow viviparity. For successful pregnancy, the uterus must not only be differentiated, but must also function optimally and any defects in uterus differentiation and/or function can lead to infertility. The homoebox gene HOXA10 has emerged to be a key player in both uterine development and its optimal functioning in adulthood. Within the Abd-B family, the posterior Hoxa genes play a dominant role in anterio-posterior segmentation of the Müllerian ducts in mammals, with Hoxa10 having a central role in uterine segmentation. In the adult endometrium, HOXA10 is expressed by endometrial cells and is regulated in a cyclic manner under the influence of ovarian steroids. During embryo implantation, expression of HOXA10 is increased in endometrial stromal cells by signals from the embryo to govern stromal cell transformation to decidual cells. Once decidualization is initiated, HOXA10 is rapidly downregulated to activate expression of pro-invasive factors to promote trophoblast invasion. We propose that HOXA10 governs embryo implantation in a three-step process: 1) acquisition of endometrial receptivity, 2) responding to signals from the blastocyst to modify receptive endometrium for decidualization 3) making the decidua conductive for trophoblast invasion and placentation. There is currently ample evidence that expression of HOXA10 is deregulated in a variety of “endometriopathies” such as endometriosis and endometrial cancers. Overall, HOXA10 appears to be the master regulator of endometrial health and a central determinant of fertility in mammals.

OVGP1 is specifically induced in the luminal epithelium at the time of embryo implantation where it regulates receptivity-related genes and aids in trophoblast adhesion.

17Study question 18 Can mitochondrial DNA (mtDNA) levels in trophectodermal cells of the blastocyst predict the 19 blastocyst quality, ploidy status, implantation rate and clinical outcomes? 20 Summary answer 21 mtDNA levels in trophectodermal cells of the blastocyst do not associate with the blastocyst 22 quality, ploidy status, implantation potential and clinical outcomes, but can differentiate between 23 aneuploid and euploid blastocysts.24 What we already know 25 mtDNA levels in the trophectodermal cells have been suggested to be associated with blastocyst 26 morphology, ploidy and implantation rates, and has been proposed as biomarker to access 27 blastocyst quality and predict clinical outcomes. However, discrepancies exist if mtDNA levels 28 could serve as a marker for the same.29 Study design and duration 30

Oviductal glycoprotein 1 (OVGP1), also called oviductin, is an oviduct-specific protein and is suggested to play a role in fertilization. Traditionally, Ovgp1 has been shown to be exclusively expressed by the oviduct; however, recent studies have demonstrated its expression in some cancers. This observation led us to hypothesize that Ovgp1 might have some extra-oviductal expression. In the current study, we evaluated the mRNA and protein expression of Ovgp1 in normal reproductive tissues of male and female mice. For the first time, we demonstrate that beyond the oviduct, Ovgp1 mRNA is expressed in the testis, epididymis and ovary, but not in the uterus, cervix, vagina, breast, seminal vesicles and prostate gland. In the testis, Ovgp1 mRNA was localized in the cells at the base of seminiferous tubules (most likely, Sertoli cells), while the protein was detected in the round and elongating spermatids. In the epididymis, Ovgp1 transcripts were localized in epididymal epithelium of the caput but not the corpus and cauda; OVGP1 protein was, however, not detected in any of the segments but was present in the epididymal sperm. In the ovary, Ovgp1 transcripts and protein were detected in the surface epithelium, granulosa cells of the preantral and the antral follicles and corpus luteum. In both, the ovary and oviduct, the expression of Ovgp1 was found to be higher at estrus stage than at diestrus stage. To the best of our knowledge, this is the first study demonstrating the extra-oviductal expression of Ovgp1. Our data suggests that, beyond fertilization, Ovgp1 might have specific roles in gonadal physiology. [Laheri S, Modi D and Bhatt P 2017 Extra-oviductal expression of oviductal.

Background: In patients undergoing assisted reproduction, levels of mitochondrial DNA (mtDNA) in the trophectodermal cells of the developing blastocyst are suggested to be associated with its ability to implant. However, discrepancies exist regarding the use of mtDNA levels as a reliable biomarker to predict outcomes of assisted reproduction. Aims: The aim of the study is to explore the association of trophectodermal mtDNA levels to determine blastocyst quality, implantation potential of blastocyst and clinical outcomes in couples who have undergone pre-implantation genetic testing for aneuploidy (PGT-A). Study Setting: Private fertility centre. Study Design: Retrospective analysis. Materials and Methods: We analysed mtDNA levels in the trophectodermal cells of 287 blastocysts from 61 couples undergoing PGT-A. The levels of mtDNA were estimated by next-generation sequencing method. mtDNA levels were correlated with maternal age, blastocyst morphology, ploidy status, implantation rates, miscarriage rate and live birth rate. Statistical Analysis Used: Linear regression and one-way ANOVA with Tukey's all column comparison test. Results: The trophectodermal mtDNA levels did not correlate with maternal age. There were no significant differences in their levels in grade 1 and grade 2 blastocysts. No significant differences were seen between mtDNA levels of implanted and non-implanted blastocysts or those blastocysts that resulted in miscarriage or live birth. However, significantly lower amounts of mtDNA were seen in euploid blastocysts as compared to that in aneuploid blastocysts. Conclusion: mtDNA levels in the trophectodermal cells of the blastocyst do not associate with blastocyst quality (grade 1 and grade 2), implantation potential and clinical outcomes but can differentiate between aneuploid and euploid blastocysts. Our study does not support the use of trophectodermal mtDNA levels as a biomarker for blastocyst quality and predictor of clinical outcomes.