Intrauterine Infusion of TGF-β1 Prior to Insemination, Alike Seminal Plasma, Influences Endometrial Cytokine Responses but Does Not Impact the Timing of the Progression of Pre-Implantation Pig Embryo Development

Abstract

Seminal plasma (SP) in the female genital tract induces changes that affect multiple reproductive processes. One of the active components in SP is the transforming growth factor β1 (TGF-β1), which has major roles in embryo development and pregnancy. Embryo transfer (ET) technology is welcomed by the pig industry provided that embryo quality at embryo collection as well as the fertility and prolificacy of the recipients after the ET is increased. This study evaluated different intrauterine infusion treatments at estrus (40 mL of SP, TGF-β1 cytokine in the extender, or the extender alone (control)) by mimicking an ET scenario in so-called “donor” (inseminated) and “recipient” (uninseminated) sows. On day 6 (day 0—onset of estrus), all “donors” were laparotomized to determine their pregnancy status (presence and developmental stage of the embryos). In addition, endometrial explants were collected from pregnant “donors” and cyclic “recipients,” incubated for 24 h, and analyzed for cytokine production. SP infusions (unlike TGF-β1 infusions) positively influenced the developmental stage of day 6 embryos. Infusion treatments differentially influenced the endometrial cytokine production, mainly in donors. We concluded that SP infusions prior to AI not only impacted the porcine preimplantation embryo development but also influenced the endometrial cytokine production six days after treatment, both in donors and recipients.

Seminal Plasma: Relevant for Fertility?

“…In the human and pig, cytokines relate to sperm viability, semen function and hence fertility [ 41 , 70 , 95 , 110 ]. As well, cytokines—probably in concert with other SP proteins [ 11 , 111 ]—play a role in modulating the uterine immune-cytokine network [ 6 , 88 , 112 , 113 , 114 , 115 , 116 , 117 ], to facilitate the transitions in immune responses by the female mentioned earlier and what appears central for successful fertility [ 93 , 102 , 118 , 119 , 120 ]. In this context, it is also worth noting the function of the adipokines secreted by white adipose tissue.…”

“…Such a steady low efficiency has, together with experimental evidence of the effects of seminal plasma on the female, called for the application of SP during or after human embryo transfer [ 205 , 206 , 207 ]. Growing evidence has established SP playing major roles in embryo development and birth rates [ 102 ], and although the matter remains unsolved for humans, the experimental evidence from various animal models has quite nicely defined these effects on the female [ 12 , 93 , 120 ] ( Figure 5 ).…”

“…Do we have evidence that the SP per se is, by inducing the changes of gene expression in the internal genitalia of the female we have already pointed out, able to mark differences in fertility when added separately from spermatozoa? The answer seems to be yes, as rates in early embryo survival [ 88 , 93 , 102 , 120 , 173 , 208 ], implantation [ 101 , 102 , 115 ], placental development [ 116 ], farrowing, litter size and even offspring development and health [ 44 ] could be improved by additional inseminations with homologous/pools of SP.…”

“…The experiment we performed compared intrauterine infusion of TGF-ß 1 with native SP prior to insemination for their effects on both endometrial cytokines and on the development of pre-implantation embryos. It was rather evident that both SP and TGF-ß 1 were able to influence endometrial cytokines, but only SP impacted pre-implantation pig embryo development, thus implying SP has a concerted action of various factors influencing embryo development by way of a modified gene expression by the female endometrium [ 120 ]. Finding out which particular factors are mechanistically most relevant seems appropriate and experimentally possible, albeit complicated.…”

Neither frozen–thawed seminal plasma nor commercial transforming growth factor‐β1 infused intra‐utero before insemination improved fertility and prolificacy in sows

“…treatment (Martinez et al, 2021), as well as modifies gene expression in the endometrium and embryos on day 6 of pregnancy, positively regulating genes and pathways associated with embryo development and immune tolerance (Martinez et al, 2019(Martinez et al, , 2020. These results are important, particularly for some porcine reproductive technologies, such as AI and embryo transfer (ET), since their implementation could improve reproductive efficiency and significantly impact the pig industry sector.…”