The transcriptomic response of bovine uterine tissue is altered in response to sperm from high- and low-fertility bulls

Abstract

Despite stringent quality control checks, some bulls with apparently normal semen quality yield lower than expected pregnancy rates. This study profiled the transcriptome and performed histological analysis of the bovine uterus in response to sperm from high fertility (HF) and low fertility (LF) bulls. Post-mortem uterine biopsies and uterine explants were collected from heifers 12 h after a fixed time artificial insemination (AI) to a synchronised oestrus with frozen–thawed semen from 5 HF (fertility rate 4.01% ± 0.25) and 5 LF (fertility rate − 11.29% ± 1.11; mean ± s.e.m.) bulls. Uterine biopsies were also collected from control (CTRL) heifers which were not inseminated. RNA-sequencing and histological analysis were performed for differential gene expression and neutrophil quantification. In the HF treatment relative to CTRL heifers there were 376 genes significantly differentially expressed in the endometrium with just one gene differentially expressed in the LF treatment relative to CTRL heifers. Comparing the HF and LF treatments directly there were 40 significantly differentially expressed genes (DEG; P < 0.05). Transcriptomic analysis shows a predominant role for the inflammatory marker Interleukin-1 alpha, which was further confirmed by immunohistochemistry. Quantification of neutrophils in the endometrium showed a significant effect of sperm, however, there was no difference in neutrophil numbers between HF and LF groups. In conclusion, this novel study clearly shows a distinct inflammatory response to sperm in the endometrium and a divergent transcriptomic response to semen from HF and LFbulls.

Transcriptomics analysis of the bovine endometrium during the perioestrus period

“…The introduction of seminal plasma upregulates inflammatory mediators in the bovine endometrium [ 104 ] indicating that this is also an essential process required to protect the uterus and promote fertility. Male fertility can affect this response, with insemination by high-fertility bulls causing alterations in the transcriptomic response relative to these induced by low-fertility bulls, particularly with respect to immune system genes [ 37 ].…”

“…Furthermore, components of seminal plasma were shown to alter the endometrial transcriptome [ 36 ]. Artificial insemination of heifers with semen from low and high-fertility bulls led to differential gene expression, with high-fertility semen leading to increased expression of genes involved in immune response and inflammation [ 37 ]. Transcriptomic studies have also identified signalling molecules supporting embryonic development in the first seven days after ovulation [ 38 ].…”