Seminal fluid effects on uterine receptivity to embryo implantation: transcriptomic strategies to define molecular mechanisms

Hon Yeung Chan; Sarah Robertson

Just Accepted

This article has been peer reviewed and accepted for publication. It is in production and has not been edited, so may differ from the final published form.

Seminal fluid effects on uterine receptivity to embryo implantation: transcriptomic strategies to define molecular mechanisms

Hon Yeung Chan , Sarah Robertson

Abstract

Embryo implantation requires both a developmentally competent embryo and a receptive uterus, and impaired uterine receptivity is a common constraint on implantation success and reproductive outcome. Ovarian steroid hormones estrogen and progesterone play a central role in establishing uterine receptivity, but other factors also contribute. One additional regulating factor is male partner seminal fluid. However, the full physiological impacts of seminal fluid on uterine receptivity and the specific molecular pathways involved are not yet completely defined. New advances in RNA-sequencing technologies provide a powerful means to examine how uterine tissues and cells respond to seminal fluid contact. Findings utilising sequencing technology provide strong cellular and molecular evidence in humans and mice that seminal fluid contact around the time of ovulation drives immune and vascular changes with potential to affect endometrial receptivity in the peri-implantation phase. This approach has led to the discovery of novel mediators and regulatory factors subsequently shown to facilitate embryo implantation in genetic mouse models enabling functional validation. Here, we summarise the evidence from recent microarray and RNA-sequencing findings that seminal fluid contact can directly and indirectly attenuate the transcriptional state of endometrial tissue during the implantation window in mice and also in humans. Progress in elucidating the female reproductive tract response to seminal fluid will improve understanding of male partner effects on endometrial receptivity, and the knowledge gained will have practical applications for achieving healthy pregnancy and offspring outcomes.

RD24162 Accepted 19 February 2025