Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pig†

Pfeiffer, Caroline A; Meyer, Ashley E; Brooks, Kelsey E.; Chen, Paula; Milano-Foster, Jessica; Spate, Lee D.; Benne, Joshua A.; Cecil, Raissa F.; Samuel, Melissa; Ciernia, L.A.; Spinka, Christine; Smith, Michael F.; Wells, Kevin D.; Spencer, Thomas E.; Prather, Randall S.; Geisert, Rodney D.

doi:10.1093/biolre/ioz192

Cited by 21 publications

(26 citation statements)

References 66 publications

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“…This indicated a new role for PGF2α secreted by the conceptuses and endometrium in supporting pregnancy establishment during the implantation period. However, the depletion of the rate-limiting enzyme prostaglandin-endoperoxide synthase 2 ( PTGS2 or COX2 ) in conceptus had no effect on either PGF2α and PGE contents in the uterine flushings or conceptus elongation in pigs ( Pfeiffer et al., 2020 ). Whether ROS were involved in this process remains unknown.…”

Section: Activation Of Redox Pathways In Porcine Conceptus Trophectodermmentioning

confidence: 99%

Reactive oxygen and nitrogen species regulate porcine embryo development during pre-implantation period: A mini-review

Luo

Yao

2021

Animal Nutrition

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Significant porcine embryonic loss occurs during conceptus morphological elongation and attachment from d 10 to 20 of pregnancy, which directly decreases the reproductive efﬁciency of sows. A successful establishment of pregnancy mainly depends on the endometrium receptivity, embryo quality, and utero-placental microenvironment, which requires complex cross-talk between the conceptus and uterus. The understanding of the molecular mechanism regulating the uterine-conceptus communication during porcine conceptus elongation and attachment has developed in the past decades. Reactive oxygen and nitrogen species, which are intracellular reactive metabolites that regulate cell fate decisions and alter their biological functions, have recently reportedly been involved in porcine conceptus elongation and attachment. This mini-review will mainly focus on the recent researches about the role of reactive oxygen and nitrogen species in regulating porcine embryo development during the pre-implantation period.

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Section: Activation Of Redox Pathways In Porcine Conceptus Trophectodermmentioning

confidence: 99%

Reactive oxygen and nitrogen species regulate porcine embryo development during pre-implantation period: A mini-review

Luo

Yao

2021

Animal Nutrition

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“…Inhibition of PG synthesis by PTGS2, the dominant cyclooxygenase enzyme in both the conceptus and endometrium, prevents conceptus elongation and results in pregnancy loss [215,216,220]. However, recent studies in other species have suggested that embryonic production of PGs is not required for early pregnancy success [229,231,232]. In Chapter Five, One important question that remains is how lipids are mobilized or transported within the ULF due to their hydrophobic nature.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, endometrial PG are more important than embryonic PG production in early pregnancy in mice [229][230][231]. Recent work in the pig has also demonstrated that conceptus-derived PG are not required for early conceptus development and can maintain pregnancy beyond day 30 [232]. Thus, while PG are undoubtedly critical regulators of conceptus elongation, the importance of conceptus production of PG in ruminant species is unclear.…”

Section: Prostaglandins In the Uterine Lumenmentioning

confidence: 99%

Extracellular vesicles, lipids, and lipoproteins in early pregnant sheep

O’Neil¹

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In sheep, pregnancy establishment encompasses conceptus elongation, implantation, and placentation. These events are regulated by factors present within the uterine luminal fluid (ULF) from the endometrial epithelium and the conceptus itself that affect proliferation, migration, attachment, and adhesion of the conceptus trophectoderm. As the peri-implantation period is especially susceptible to pregnancy loss, it is essential to understand the various components and functional roles of substances within the ULF. The central hypothesis of this dissertation is that lipids and lipid associated macromolecules are components of the ULF and mediate endometrial-embryonic crosstalk and regulate conceptus development. This work sought to identify, characterize, and/or determine the roles of: (1) extracellular vesicles (EVs); (2) lipids and metabolites; (3) prostaglandins (PGs); and (4) apolipoproteins present within the ULF of ewes during early gestation. Collectively, the present studies established that: (1) EVs increase within the ULF during the estrous cycle but are depleted in the uterine lumen of pregnant ewes due to uptake by the elongating conceptus; (2) the lipid and protein cargo of uterine EVs is diverse and altered by pregnancy; (3) uterine EVs regulate cellular processes in the conceptus trophectoderm and endometrium including cell proliferation and secretions; (4) various lipids (specifically phospholipids, ceramides, and triglycerides) and metabolites are elevated in the ULF of pregnant ewes; (5) the conceptus lipidome and metabolome is distinct from the ULF and endometrium suggesting selective uptake of ULF substances; (6) the production of PGs by PTGS2 in the conceptus is not required for conceptus elongation; (7) the secretion of APOA1 by the conceptus does not mobilize endometrial lipids into the ULF and is not required for early pregnancy development or survival. Collectively, these studies highlight the complex and dynamic composition of the ULF and support the overall hypothesis that lipids and lipid-associated macromolecules are critical components of the ULF that mediate conceptus-endometrial crosstalk and regulate important developmental processes in the conceptus. Future investigation and expansion of these findings will fill crucial gaps in our knowledge of early pregnancy events and may provide biomarkers or help develop therapies to improve pregnancy outcomes and reproductive efficiency in agricultural species.

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“…Despite the decreased PG synthesis, PTGS2 -/conceptuses were able to elongate, establish pregnancy, and maintain pregnancy to day 35 of gestation. Although PTGS2 -/-PG production was significantly decreased on day 14 and 17 of pregnancy, uterine lumen flush (ULF) content of PG was not affected (Pfeiffer et al 2019). ULF content of PG was expected to be similar between control and edited conceptus pregnancies as the maternal endometrium is the major contributor of PG into the uterine lumen.…”

Section: Prostaglandin Role In Maternal Recognition Of Pregnancymentioning

confidence: 99%

“…Extracted RNA was treated with RNase Free DNase Set (Qiagen, 79256) to eliminate genomic DNA contamination. Quantity and quality of RNA and DNA in the samples were established by using a NanoDrop ND-1000 spectrophotometer and visualization of conceptus DNA bands on a 2% ethidium bromide agarose gel and RNA with a 1% ethidium bromide agarose and a 1% bleach integrity gel as previously described (Pfeiffer et al 2019).…”

Section: Total Rna Genomic Dna and Protein Isolationmentioning

confidence: 99%

Conceptus interferon gamma is essential for pregnancy maintenance in the pig

Johns¹

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Establishment and maintenance of pregnancy in the pig is a complex process that relies on adequate communication between the conceptus and maternal uterine endometrium. During the peri-implantation period, the conceptuses produce and secrete estrogens, interleukin 1 beta 2, prostaglandins and other biological factors into the uterine lumen that change the uterine epithelium to become receptive to the attaching conceptuses as well as promote proper conceptus development. Following elongation, beginning on day 12 of pregnancy, the conceptus is known to secrete two different types of interferons. The pig conceptus secretes both type I (interferon delta, IFND) and type II (interferon gamma, IFNG) interferons during this time. CRISPR/Cas9 gene editing and somatic cell nuclear transfer (SCNT) technologies were used to create an IFNG loss-of-function study in pigs. Blastocyst stage embryos that were IFNG[superscript +/+] or IFNG[superscript -/-] were transferred into recipient gilts and their reproductive tracts were collected on days 15 and 17 of pregnancy. Elongated conceptuses were flushed from recipient gilts on day 15 IFNG[superscript +/+] (4/4) and IFNG[superscript -/-] (4/4) recipient gilts. On day 17 of pregnancy, all IFNG[superscript +/+] recipient gilts (4/4) contained elongated viable conceptuses; however, conceptuses were only recovered from 2 of 8 IFNG[superscript -/-] embryo recipient gilts. In all IFNG[superscript -/-] pregnancies, the conceptuses were thin and fragmented compared to IFNG+/+ conceptuses. Additionally, the reproductive tracts that received IFNG[superscript -/-] conceptuses which were not pregnant on day 17 appeared hyperemic, inflamed and edematous. IFNG was localized to the trophectoderm of IFNG[superscript +/+] conceptuses on both day 15 and 17 of pregnancy. However, IFNG expression was not detected in IFNG[superscript -/-] conceptuses on either day 15 or day 17 of pregnancy. Conceptus IFNG mRNA expression was significantly affected by genotype (P [equals] 0.0006) and day (P [less than] 0.0001). Total IFNG was significantly lower (P [equals] 0.0018) in ULF of IFNG[superscript -/-] embryo recipient gilts compared to IFNG[superscript +/+] embryo recipient gilts. IFNG[superscript +/+] conceptuses induced endometrial folding and recruited large numbers of immune cells to the endometrial stroma beneath the site of conceptus attachment compared to less endometrial folding and presence of immune cells in IFNG[superscript -/-] pregnancies on day 15. An additional group of recipient gilts received either IFNG[superscript +/+] embryos (n [equals] 6) or both IFNG[superscript -/-] and IFNG[superscript +/+] embryos (n [equals] 5) to determine if the presence of IFNG producing conceptuses could rescue the IFNG-/- embryos beyond day 17 of pregnancy. On day 30 of pregnancy, 3/6 of IFNG[superscript +/+] embryo recipient gilts contained 3-4 viable embryos, however, only 1 of 5 IFNG[superscript -/-] and IFNG[superscript +/+] cotransferred recipient gilts maintained pregnancy to day 30. Genotyping indicated that all five (1 healthy, 4 degenerating) embryos were IFNG[superscript +/+]. These results indicate conceptus IFNG production is not essential for early conceptus development, rapid elongation or establishment of pregnancy. However, conceptus IFNG production does appear to be necessary for survival during the period of placental attachment beyond day 15.

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Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pig†

Cited by 21 publications

References 66 publications

Reactive oxygen and nitrogen species regulate porcine embryo development during pre-implantation period: A mini-review

Reactive oxygen and nitrogen species regulate porcine embryo development during pre-implantation period: A mini-review

Extracellular vesicles, lipids, and lipoproteins in early pregnant sheep

Conceptus interferon gamma is essential for pregnancy maintenance in the pig

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