Publications by authors named "Craig A Gifford"

7 Publications

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BEEF SPECIES-RUMINANT NUTRITION CACTUS BEEF SYMPOSIUM: Maternal immune modulation prior to embryo arrival in the uterus is important for establishment of pregnancy in cattle1.

J Anim Sci 2019 Jul;97(8):3605-3610

Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM.

In 1953, Sir Peter Medawar first recognized the allogeneic properties of a developing conceptus and rationalized that an "immune-tolerant" physiological state must exist during pregnancy. Early theories speculated that the conceptus evaded the maternal immune system completely, but 40 yr after Medawar's observations, Wegmann proposed that the maternal immune system shifts the cytokine profile away from inflammatory cytokine production when an embryo is present. The economic consequences and production losses of subfertile animals have been well documented in studies evaluating calving distribution. Despite advances in understanding infertility or subfertility, few technologies exist to identify subfertile animals or improve fertility beyond hormonal intervention associated with synchronization protocols. Work in rodents and some livestock species indicates that the uterine immune cell population shifts dramatically after copulation and these early immune-modulated events establish a receptive uterine environment. Clearly, as evident in embryo transfer, the presence of a conceptus is sufficient to establish communication for pregnancy establishment but does not rule out the importance of other physiological events to prime the maternal immune system prior to blastocyst arrival in the uterus. In support of this concept, work in our laboratory and by others has demonstrated that autologous intrauterine transfer of peripheral immune cells prior to embryo transfer can increase pregnancy rates and accelerate conceptus development in women and cattle. Understanding aberrant immune regulation in subfertile animals may provide markers for subfertility or targets for clinical intervention to enhance fertility, particularly when using reproductive technologies.
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http://dx.doi.org/10.1093/jas/skz160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667245PMC
July 2019

Lipopolysaccharide modulation of ovarian hormonal profile.

Transl Anim Sci 2018 Sep 27;2(Suppl 1):S31-S34. Epub 2018 Sep 27.

Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM.

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http://dx.doi.org/10.1093/tas/txy027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200988PMC
September 2018

Intraovarian WNT3A modulates estrogen-mediated estrus behavior in cattle.

Transl Anim Sci 2018 Sep 27;2(Suppl 1):S19-S21. Epub 2018 Sep 27.

Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM.

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http://dx.doi.org/10.1093/tas/txy026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200525PMC
September 2018

ASAS-SSR Triennial Reproduction Symposium: Looking Back and Moving Forward-How Reproductive Physiology has Evolved: WNTs role in bovine folliculogenesis and estrogen production.

J Anim Sci 2018 Jun;96(7):2977-2986

Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM.

Appreciation of mechanisms that affect steroidogenesis is critical to identifying compromising signals that may decrease reproductive efficiency. Follicle maturation and steroidogenesis requires coordinated actions from the pituitary gonadotropins and local ovarian signaling molecules. β-Catenin (CTNNB1), the lynchpin molecule of canonical wingless-type mouse mammary tumor virus integration site (WNT) signaling, is required for maximal gonadotropin stimulation of steroid production from granulosa (GC) and luteal cells. WNTs are locally secreted glycoproteins involved in ovarian development and folliculogenesis. In cultured bovine GC, WNT2 and AKT mRNAs and CTNNB1 protein increase after FSH stimulation. Likewise, CTNNB1 protein is greater in large antral follicles with high intrafollicular estradiol concentrations, suggesting the hormonal milieu responsible for increased estradiol content modulates CTNNB1 accumulation. In addition, concurrent treatment of FSH and WNT3A in GC results in reduced steroidogenic enzymes and ovarian differentiation factors. It is likely that FSH regulation of WNT signaling establishes a negative feedback loop to ensure CTNNB1 remains controlled. To explore the mechanism resulting in this inhibitory effect, AKT pathway modulators were utilized and unveiled a requirement for AKT activity in FSH-mediated CTNNB1 accumulation. Cells treated with FSH, IGF-1, and IGF-1 + FSH had increased CTNNB1 protein accumulation compared with controls. Similarly, estradiol medium concentrations increased in treated cells compared with non-treated controls, while co-treatment of FSH and IGF-1 with the AKT inhibitor LY294002 reduced CTNNB1 and estradiol production. Subsequent studies evaluated whether FSH regulation of CTNNB1 occurs through a specific phosphorylation event. In bovine GC, phosphorylation of CTNNB1 at Ser-552 was demonstrated in FSH-treated cells, whereas IGF-1 treatment did not phosphorylate CTNNB1 Ser-552. Data indicate that in cattle phosphorylation on CTNNB1 Ser-552 is a protein kinase A (PKA) dependent, protein kinase B (AKT) independent event. Data suggest that CTNNB1 regulated by AKT is a fundamental component of FSH-induced estrogen production. However, AKT's role in estradiol synthesis does not appear to be through phosphorylation of CTNNB1 Ser-552. The complex interplay between FSH and ovarian WNT/CTNNB1 signaling is key to regulation of follicle maturation and steroidogenesis.
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http://dx.doi.org/10.1093/jas/sky135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095258PMC
June 2018

Canonical WNT signaling inhibits follicle stimulating hormone mediated steroidogenesis in primary cultures of rat granulosa cells.

PLoS One 2014 17;9(1):e86432. Epub 2014 Jan 17.

Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma, United States of America.

Beta-catenin (CTNNB1), a key component of wingless-type mouse mammary tumor virus integration site family (WNT) signaling, participates in follicle stimulated hormone-mediated regulation of estrogen (E2) production. The purpose of these studies was to determine if CTNNB1's contribution to FSH-mediated steroidogenesis in primary rat granulosa cells was due in part to extracellular stimulation of the canonical WNT signaling pathway. To achieve this purpose, primary cultures of rat granulosa cells were exposed to vehicle or a canonical member of the WNT signaling pathway, WNT3A, before co-culture and in the presence or absence of FSH for 24 h. Activation of the canonical WNT signaling pathway was determined by dose-dependent induction of Axin2 mRNA expression and stimulation of the CTNNB1/T cell factor promoter-reporter TOPflash. WNT pathway induction was demonstrated at doses of 50 and 500 ng/mL of WNT3A. Granulosa cells treated with WNT3A in combination with FSH had enhanced CTNNB1/T cell factor transcriptional activity above cells treated with WNT3A alone. Steroidogenic enzymes and ovarian differentiation factor mRNAs were quantified via quantitative PCR. Expression of steroidogenic enzyme mRNAs aromatase (Cyp19a1), P450 side chain cleavage (Cyp11a1), and steroidogenic acute regulatory protein (Star) were increased following FSH treatment. Co-incubation of WNT3A and FSH reduced the ability of FSH to stimulate steroidogenic enzymes and subsequent E2 and progesterone (P4) production. Concomitant activation of FSH and WNT pathways results in marked reduction of ovarian differentiation factors, LH receptor (Lhcgr) and inhibin-alpha (Inha). Therefore, WNT inhibits FSH target genes and steroid production associated with maturation and differentiation of the ovarian follicle.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086432PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895028PMC
September 2014

Evaluation of steroidogenic capacity after follicle stimulating hormone stimulation in bovine granulosa cells of Revalor 200® implanted heifers.

J Anim Sci Biotechnol 2014 Jan 7;5(1). Epub 2014 Jan 7.

Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.

Background: Heifers not used as breeding stock are often implanted with steroids to increase growth efficiency thereby altering hormone profiles and potentially changing the environment in which ovarian follicles develop. Because bovine granulosa cell culture is a commonly used technique and often bovine ovaries are collected from abattoirs with no record of implant status, the objective of this study was to determine if the presence of an implant during bovine granulosa cell development impacts follicle stimulating hormone-regulated steroidogenic enzyme expression. Paired ovaries were collected from 16 feedlot heifers subjected to 1 of 3 treatments: non-implanted (n = 5), Revalor 200 for 28 d (n = 5), or Revalor 200 for 84 d (n = 6). Small follicle (1 to 5 mm) granulosa cells were isolated from each pair and incubated with phosphate buffered saline (n = 16) or 100 ng/mL follicle stimulating hormone (n = 16) for 24 h.

Results: Granulosa cells of implanted heifers treated with follicle stimulating hormone produced medium concentrations of progesterone similar (P = 0.22) to non-implanted heifers, while medium estradiol concentrations were increased (P < 0.10) at 28 and 84 d compared to non-implanted heifers indicating efficacy of treatment. Additionally, real-time PCR analysis in response to follicle stimulating hormone treatment demonstrated a decrease in steroidogenic acute regulatory protein (P = 0.05) mRNA expression in heifers implanted for 84 d and an increase in P450 side chain cleavage mRNA in granulosa cells of heifers implanted for 28 (P < 0.10) or 84 d (P < 0.05) compared to non-implanted females. However, no difference in expression of 3-beta-hydroxysteroid dehydrogenase (P = 0.57) and aromatase (P = 0.23) were demonstrated in implanted or non-implanted heifers.

Conclusions: These results indicate follicles which develop in the presence of high concentrations of androgenic and estrogenic steroids via an implant tend to demonstrate an altered capacity to respond to follicle stimulating hormone stimulation. Thus, efforts should be made to avoid the use of implanted heifers to study steroidogenesis in small follicle granulosa cell culture systems.
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http://dx.doi.org/10.1186/2049-1891-5-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901558PMC
January 2014

Effects of early conceptus signals on circulating immune cells: lessons from domestic ruminants.

Am J Reprod Immunol 2010 Oct 23;64(4):245-54. Epub 2010 Aug 23.

Department of Dairy and Animal Science, Center for Reproductive Biology and Health, Pennsylvania State University, University Park, PA, USA.

While there are few similarities between mechanisms for extending corpus luteum (CL) function during early pregnancy in ruminants and primates, there is increasing evidence that conceptus-immune crosstalk in ruminants and primates affects the function of circulating immune cells at the very earliest stages of pregnancy. Most notable are changes in immune cell phenotypes with increased numbers of cells exhibiting the T regulatory phenotype and suppression of Th1 cytokines that promote tolerance to paternal alloantigens. Until recently, interferon τ produced by the ruminant trophectoderm was thought to act exclusively on the uterine endometrium; however, it is now clear that this unique embryonic interferon escapes the uterus and alters gene expression in the CL and in peripheral blood leukocytes (PBL). In fact, a large number of interferon-stimulated genes are now known to be increased during early pregnancy in PBL. What is not known is how this conceptus-immune system cross-talk affects maternal immune status outside the reproductive tract. It is attractive to hypothesize that some of these effects are designed to counter-balance progesterone-induced immunosuppression so as not to place the dam at a greater risk of infection on top of the tremendous stresses already induced by pregnancy. Furthermore, recent evidence suggests that pregnancy induced changes in peripheral immune cells may aid in orchestrating establishment of pregnancy. Existing evidence points toward a greater convergence of systemic immune responses to early pregnancy signaling between ruminants and primates.
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http://dx.doi.org/10.1111/j.1600-0897.2010.00912.xDOI Listing
October 2010