Effect of seminal plasma infusion into the vagina on the normalization of endometrial epidermal growth factor concentrations and fertility in repeat breeder dairy cows

Abstract

Epidermal growth factor (EGF) concentrations in the uterus show two peaks on days 2-4 and 13-14 during the estrous cycle in fertile cows. Loss of the two peaks has been linked to reduced fertility in repeat breeder cows. This study aimed to examine the effect of seminal plasma (SP) on normalizing endometrial EGF concentrations and restoring fertility in repeat breeder cows with low EGF concentrations on day 3. In study 1, we examined the effect of the deposition sites (the vagina and uterus) of SP on the endometrial EGF concentrations in repeat breeder cows. SP infusion into the vagina, but not uterus, on the first day of the estrus cycle (day 0) normalized the endometrial EGF concentrations (≥ 4.7 ng/g tissue weight) on day 3. In study 2, the effect of SP volume (0.5 and 10 ml of SP and 0.5 ml of SP diluted to 10 ml) on EGF concentration was examined. All groups with SP infusion had increased EGF concentrations on day 3, and cows with 10 ml of SP and 0.5 ml of SP diluted to 10 ml showed the highest levels of EGF concentrations. In study 3, we examined the effect of SP infusion on fertility. SP infusion normalized two peaks of endometrial EGF concentrations in about 60% of repeat breeder cows and produced more pregnancies than the controls (44.4 vs. 19.4%). Therefore, we concluded that SP may contain an activity to normalize the EGF profile and restore fertility in repeat breeder cows with altered EGF profiles.

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

“…The lack of a response to mating with a vasectomized bull, together with the discovery of genes that were regulated by mating to intact bulls, led to the analysis of tissues that have direct contact with seminal fluid (i.e., the vagina). The ejaculation site during natural conception is an important factor to take into consideration since a recent study has shown that SP infusion into the vagina, but not into the uterus, could influence the levels of endometrial epidermal growth factor (Badrakh et al, 2020), which has been associated with fertility restoration in repeat breeder cows (Katagiri and Takahashi, 2006). In this sense, we were also interested in studying how far into the reproductive tract these changes could be observed, so gene expression analysis in the oviductal ampulla was also undertaken.…”

“…As mentioned above, it is questionable whether SP reaches the uterus during mating in cattle, so results obtained from the infusion of SP into the uterus may not be representative of physiological conditions. Indeed, recently it has been shown that infusion of SP into the vagina, but not into the uterus, modifies endometrial levels of epidermal growth factor (Badrakh et al, 2020), which highlights the importance of considering the ejaculate deposition site in natural conception in these studies. 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).…”

Effect of Exposure to Seminal Plasma Through Natural Mating in Cattle on Conceptus Length and Gene Expression

“…These factors could travel through local circulation to elicit changes in other reproductive organs, as seems to be the case in pigs, rodents, and cattle. In the bovine, SP infusion into the vagina, but not the uterus, induces an increase in endometrial epidermal growth factor concentrations (Badrakh et al, 2020). Whereas mating (in the mouse) or infusion of SP (in the sow) have been shown to have an effect on ovarian function (Gangnuss et al, 2004;O'Leary et al, 2006).…”

Effects of heat stress on the endometrial epidermal growth factor profile and fertility in dairy cows

“…The pregnancy rate of ET in summer may be further improved by treatment targeting the uterine EGF expression [40,41] or an intensive cooling around the day of estrus, which has been shown to increase the conception rate of AI during the summer period [76].…”