Mating to Intact, but Not Vasectomized, Males Elicits Changes in the Endometrial Transcriptome: Insights From the Bovine Model

Sandra Recuero,José María Sánchez,Michael Mcdonald,Thomas E Spencer,Beatriz Fernandez-Fuertes,Sandra Bagés-Arnal,Pat Lonergan,Susanta K Behura,Marc Yeste,Yentel Mateo-Otero,David A Kenny

doi:10.3389/fcell.2020.00547

Abstract

An appropriate female reproductive environment is essential for pregnancy success. In several species, including mice, pigs and horses, seminal plasma (SP) components have been shown to modulate this environment, leading to increased embryo viability and implantation. Due to the characteristics of mating in the aforementioned species, SP comes into direct contact with the uterus. However, it is questionable whether any SP reaches the uterus in species that ejaculate inside the vagina, such as humans and cattle. Hence, we hypothesized that sperm, perhaps acting as a vehicle for SP factors, play a more important role in the modulation of the maternal uterine environment in these species. In addition, changes elicited by SP and/or sperm may originate in the vagina and propagate to more distal regions of the female reproductive tract. To test these hypotheses, a bovine model in which heifers were mated to intact or vasectomized bulls or were left unmated was used. RNA-sequencing of endometrial samples collected 24 h after mating with a vasectomized bull did not reveal any differentially expressed genes (DEGs) in comparison with control samples. However, the endometrium of heifers mated with intact bulls exhibited 24 DEGs when compared to heifers mated with vasectomized bulls, and 22 DEGs when compared to unmated control heifers. The expression of a set of cytokines (IL6, IL1A, IL8, and TNFA) and candidate genes identified in the endometrial RNA-sequencing (PLA2G10, CX3CL1, C4BPA, PRSS2, BLA-DQB, and CEBPD) were assessed by RT-qPCR in the vagina and oviductal ampulla. No differences in expression of these genes were observed between treatments in any region. However, mating to both intact and vasectomized bulls induced an increase in IL1A and TNFA expression in the vagina compared to the oviduct. These data indicate that sperm, but not secretions from the accessory glands alone, induce modest changes in endometrial gene expression after natural mating in cattle. However, it is not clear whether this effect is triggered by inherent sperm proteins or SP proteins bound to sperm surface at the time of ejaculation.

Highlights

Embryonic loss is a major contributor to pregnancy failure in livestock species and humans, ranging from 20 to 40% (Macklon et al, 2002; Wiltbank et al, 2016)
We recently reported a modest increase in conceptus length in embryos that developed from Day 7 to Day 14 in the uterus of heifers mated to a vasectomized bull in comparison to unmated heifers (Mateo-Otero et al, 2020)
Regarding the heifers mated with vasectomized bulls, fresh ovulation was found in six animals and only two presented a pre-ovulatory follicle

Summary

Introduction

Embryonic loss is a major contributor to pregnancy failure in livestock species and humans, ranging from 20 to 40% (Macklon et al, 2002; Wiltbank et al, 2016). The increase in CD4+CD25+ is not observed when females are mated to vasectomized or seminal-vesicle-excised males, suggesting that this expansion is driven by secretions from the male accessory glands (Robertson et al, 2009) This effect likely explains why mating increases maternal tolerance toward paternal major histocompatibility complex (MHC) antigens (Robertson et al, 2009), which improves the ability of the semi-allogenic embryo to implant and develop normally in this species (Bromfield et al, 2014; Watkins et al, 2018). In horses, a pivotal role of SP in protecting spermatozoa from neutrophil phagocytosis in the uterus has been suggested, improving fertility in this environment (Troedsson et al, 2002; Alghamdi et al, 2004)

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