Early luteal phase progestin concentration influences endometrial function in pregnant mares

Beyer, T.; Rink, B. Elisabeth; Scarlet, D.; Walter, Ingrid; Kunert, Steffen; Aurich, Christine

doi:10.1016/j.theriogenology.2018.11.018

Cited by 21 publications

(14 citation statements)

References 36 publications

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“…To what extent, L‐arginine supplementation enhanced embryonic growth to a point that improves conceptus survival thus remains open. In early pregnant mares with an experimentally reduced luteal function, lysine and isoleucine but not arginine content in uterine fluid was reduced (Beyer et al, ), adding further evidence that arginine may be less important during early pregnancy in horses than in certain other species.…”

Section: Discussionmentioning

confidence: 96%

Effects of dietary L‐arginine supplementation to early pregnant mares on conceptus diameter—Preliminary findings

Aurich

Köhne

Wulf³

et al. 2019

Reprod Domestic Animals

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ContentsThe importance of the amino acid L‐arginine (ARG) for conceptus growth and litter size has been demonstrated in various species. L‐arginine is part of embryo‐derived polyamines, a substrate for nitric oxide synthase and stimulates protein synthesis by the embryo. In the present study, we have investigated whether dietary L‐arginine supplementation stimulates early conceptus growth in mares. Warmblood mares with singleton pregnancies received either an arginine‐supplemented diet (approximately 0.0125% of body weight, n = 12) or a control diet (n = 11) from days 15 to 45 after ovulation. Diameter of the embryonic vesicle (days 14, 17, 20 of pregnancy) and size of the embryo respective foetus (length and maximal diameter, days 25–45 of pregnancy at 5‐day intervals) were determined by transrectal ultrasound. At foaling, weight and size of the foal and the placenta were determined. Blood for determination of equine chorionic gonadotrophin (eCG) and progestin concentrations was collected repeatedly. Neither eCG nor progestin concentration in plasma of mares differed between groups at any time. No effects of arginine treatment on diameter of the embryonic vesicle between days 14 and 20 of pregnancy were detected. Diameter of the embryo/foetus on days 40 to 45 of pregnancy strongly tended to be enhanced by arginine supplementation (p = 0.06). Weight and size of neither the foal nor placenta at birth differed between groups. In conclusion, L‐arginine supplementation was without negative effects on early equine embryos and may support embryonic growth at the beginning of placentation.

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Section: Discussionmentioning

confidence: 96%

Effects of dietary L‐arginine supplementation to early pregnant mares on conceptus diameter—Preliminary findings

Aurich

Köhne

Wulf³

et al. 2019

Reprod Domestic Animals

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“…Timely progesterone receptor downregulation is an important step in the preparation of the endometrium for early pregnancy and placentation [9,10]. This has also been demonstrated in horses [5,7,11].…”

Section: Introductionmentioning

confidence: 83%

“…Treatment of mares with PGF 2α and its analogues during the early postovulatory phase does not induce complete luteolysis, but results in markedly reduced plasma progestogen concentrations, followed by a steady progestogen increase reflecting a certain resumption of luteal function [5,7,[12][13][14][15]. We could recently demonstrate that the experimentally reduced early postovulatory progestogen concentration in pregnant mares was not only associated with delayed conceptus development, but also with an increased incidence of luteal phase ovulations between days 11 and 15 after ovulation [7].…”

Section: Introductionmentioning

confidence: 97%

“…An association with low progesterone concentrations has been suggested [4]. There is, however, evidence that low postovulatory progesterone concentrations in mares may be also associated with increased pregnancy loss [5][6][7]. In several species, the concentration of plasma progesterone during the first days after ovulation substantially influences endometrial function with regard to conceptus nutrient supply [8] because it induces downregulation of endometrial progesterone receptors.…”

Section: Introductionmentioning

confidence: 99%

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Diestrous Ovulations in Pregnant Mares as a Response to Low Early Postovulatory Progestogen Concentration

Okada

Kapš

Quesada

et al. 2020

Animals

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Spontaneous prolongation of the luteal phase has been described in horses, but the underlying causes are still unclear. The present study investigated details of gonadotrophin and progestogen secretion in pregnant mares (n = 11) with or without experimentally reduced early postovulatory luteal function. From days 0 to 3 after ovulation, they were treated with the prostaglandin F2α (PGF2α) analogue cloprostenol or left untreated. After conceptus collection on day 34, they were assigned to the opposite treatment. Mares were affiliated to the group primary corpus luteum (n = 6) or diestrous corpus luteum (n = 5) depending on diestrous corpus luteum (CL) detection in the PGF pregnancy. For statistical comparisons, a p-value < 0.05 was significant. There was an effect of treatment (p < 0.01), but not of group on progestogen concentration. The concentration of LH was higher in PGF-treated than in untreated pregnancies (p < 0.05), but did not differ between groups. The FSH concentration did not differ between groups nor treatments. The total luteal tissue area was greater in mares with a diestrous ovulation during the PGF treatment pregnancy. Low progestogen concentration in the early postovulatory phase diminish the negative feedback on the hypothalamic-pituitary axis in early pregnancy and, thus, stimulate a luteal tissue response. Detection of secondary CL at the time of pregnancy examination in mares may reflect that early post-ovulatory progestogen concentrations were low.

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“…In horses, the postovulatory rise in P4 is much more rapid (approximately 24 h after ovulation [29]) than in cattle (approximately 5 days [30]) such that there is very little scope for advancing the onset of the progesterone rise to accelerate conceptus development or identify P4-induced endometrial factors that promote conceptus growth. Moreover, simply raising the P4 concentration during early diestrus by providing exogenous P4 does not appear to affect endometrial gene expression or function [31,32]. An alternative approach to temporally separating P4 and conceptus-induced effects on endometrial function is asynchronous embryo transfer (ET), i.e., transferring an embryo to a more advanced (positive asynchrony) or retarded (negative asynchrony) uterine environment.…”

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confidence: 99%

Asynchronous Embryo Transfer Followed by Comparative Transcriptomic Analysis of Conceptus Membranes and Endometrium Identifies Processes Important to the Establishment of Equine Pregnancy

Gibson

Ruijter-Villani

Bauersachs

et al. 2020

IJMS

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Preimplantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to 'extracellular exosome'. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently upregulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.Int. J. Mol. Sci. 2020, 21, 2562 2 of 25 to be essential for MRP, since restricting migration to a single uterine horn results in failure to avert luteolysis [7]. In the absence of pregnancy, luteolysis occurs between approximately days 13 and 16 as a result of pulses of prostaglandin F2α (PGF2α) released by the endometrium following the establishment of an oxytocin-PGF2α positive feedback loop [8,9]. To prevent luteal regression, the embryo's MRP signal must prevent the cyclical increase in oxytocin sensitivity that starts at approximately day 10 after ovulation [10,11]. Although the identity of the equine embryonic MRP signal(s) remains unknown [12], it is increasingly clear that MRP involves the transient suppression of PGF2α release by a combination of inhibiting prostaglandin-endoperoxidase-synthase 2 expression (PTGS2; the rate-limiting enzyme in PGF2α synthesis) and delaying the upregulation of the endometrial oxytocin receptors critical to the oxytocin-PGF2α loop needed to generate luteolytic pulses of PGF2α [8,10,13].Recent transcriptomic and proteomic analyses have improved our understanding of embryo-maternal communication during the conceptus migration and MRP phase. Studies have compared gene expression in endometrium between cycling and pregnant mares on days 8 an...

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Early luteal phase progestin concentration influences endometrial function in pregnant mares

Cited by 21 publications

References 36 publications

Effects of dietary L‐arginine supplementation to early pregnant mares on conceptus diameter—Preliminary findings

Effects of dietary L‐arginine supplementation to early pregnant mares on conceptus diameter—Preliminary findings

Diestrous Ovulations in Pregnant Mares as a Response to Low Early Postovulatory Progestogen Concentration

Asynchronous Embryo Transfer Followed by Comparative Transcriptomic Analysis of Conceptus Membranes and Endometrium Identifies Processes Important to the Establishment of Equine Pregnancy

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