Preeclampsia is a disorder specific of the human being that appears after 20 weeks of pregnancy, characterized by new onset of hypertension and proteinuria. Abnormal placentation and reduced placental perfusion associated to impaired trophoblast invasion and alteration in the compliance of uterine spiral arteries are the early pathological findings that are present before the clinical manifestations of preeclampsia. Later on, the endothelial and vascular dysfunction responsible of the characteristic vasoconstriction of preeclampsia appear. Different nutritional risk factors such as a maternal deficit in the intake of calcium, protein, vitamins and essential fatty acids, have been shown to play a role in the genesis of preeclampsia, but also an excess of weight gain during pregnancy or a pre-pregnancy state of obesity and overweight, which are associated to hyperinsulinism, insulin resistance and maternal systemic inflammation, are proposed as one of the mechanism that conduce to endothelial dysfunction, hypertension, proteinuria, thrombotic responses, multi-organ damage, and high maternal mortality and morbidity. Moreover, it has been demonstrated that pregnant women that suffer preeclampsia will have an increased risk of future cardiovascular disease and related mortality in their later life. In this article we will discuss the results of studies performed in different populations that have shown an interrelationship between obesity and overweight with the presence of preeclampsia. Moreover, we will review some of the common mechanisms that explain this interrelationship, particularly the alterations in the L-arginine/nitric oxide pathway as a crucial mechanism that is common to obesity, preeclampsia and cardiovascular diseases.
The objective of the present study was to evaluate the superovulatory response and embryo production in beef donors using 8 twice-daily injections of FSH or an alternative protocol in which the last 4 FSH injections were replaced with a single injection of eCG. In Exp. 1, 12 mature Bonsmara donor cows, with a body condition score between 3 and 4 (1 to 5 scale) were superstimulated twice every 46 days in a crossover design (i.e. in each experiment all cows received 2 treatments and the 2 treatments were equally represented in each replicate). On Day 0 a.m., all donors received an intravaginal device with 1.2g of progesterone (Diprogest 1200®, Zoovet, Santa Fe, Argentina), along with 50mg of progesterone i.m (Progestar®, Zoetis, Buenos Aires, Argentina) and 5mg of oestradiol-17β (17βOestradiol®, Rio de Janeiro, Argentina) IM. On Day 4 a.m., the superstimulatory treatments were initiated and donors in the control group received 8 applications of FSH (Folltropin-V, Vetoquinol, Lure, France), IM (total dose: 300mg NIH-FSH-P1) in a twice-daily decreasing dosage schedule over 4 days (i.e. 60, 60, 50, 50, 30, 30, 10, and 10mg, respectively). Donors in the FSH+800 eCG group received only the first 4 applications of FSH (i.e. 60, 60, 50 and 50mg, respectively) and on Day 6 a.m. they received 800IU of eCG (Novormón®, Zoetis) IM in a single dose. All donors received 500μg of cloprostenol (Ciclase DL®, Zoetis) IM on Day 6 a.m. and p.m., and the intravaginal devices were removed on Day 7 a.m. All cows also received 100μg of gonadorelin acetate (GnRH, Gonasyn gdr, Zoetis) on Day 8 a.m. and were inseminated with frozen-thawed semen from 2 bulls 12 and 24h later. On Day 15, ova/embryos were collected and evaluated according to the IETS standards. The data were analysed by GLMM (Infostat, 2018). In Exp 2., 18 Bonsmara donors with similar conditions as those in Exp. 1 were superovulated twice in a crossover design. Cows in both groups received similar treatments to those in the FSH+eCG treatment of Exp. 1, except that the total dosage of FSH was 200mg (i.e. 60, 60, 40, and 40mg, respectively) and the eCG given on Day 6 a.m. was either 600IU (group 1) or 800IU (group 2). In Exp 1., the FSH (control) group had a higher (P<0.01) number of fertilized oocytes, but there were no differences in the other end points evaluated (Table 1). In Exp. 2, no differences were found between FSH+800 eCG and FSH+600 eCG groups in any of the parameters evaluated. In conclusion, the replacement of the last 4 injections of FSH by a single dose of eCG decreases the number of treatments required in a superovulation program without negatively affecting the production of transferable embryos. Table 1.Embryo production (means±s.e.m.) in Bonsmara donors treated with FSH or FSH+eCG
A retrospective analysis evaluated pregnancy rates and embryo losses with in vitro-produced embryos in a commercial embryo transfer program on 15 different beef farms. Recipients were beef cows and heifers (n = 1841) that were synchronized with 5 different protocols and transferred at a fixed-time (FTET). Recipients were examined by ultrasonography on Day 0, and those with a corpus luteum (CL) or a follicle ≥8 mm in diameter and with body condition score 2 to 4 (1 to 5 scale) were synchronized. The synchronization treatments were as follows. (T1) Recipients received an intravaginal device with 0.5 g of progesterone plus 2 mg of oestradiol benzoate on Day 0; device removal, plus 500 μg of cloprostenol (prostaglandin F2α), 400 IU of eCG, and 0.5 mg of oestradiol cypionate on Day 8; and FTET on Day 17. (T2) This treatment was similar to T1 but 1 mg of oestradiol cypionate was injected at device removal instead of 0.5 mg of oestradiol cypionate. (T3) This treatment was similar to T1 except that animals were tail-painted on Day 8 and observed on Day 10. Those with the tail-paint intact on Day 10 received 100 μg of gonadorelin (gonadotropin-releasing hormone) and all recipients were FTET on Day 17. (T4) Recipients received a progesterone device on Day 0; device removal, prostaglandin F2α, and eCG on Day 5; gonadotropin-releasing hormone on Day 8; and FTET on Day 15. (T5) Recipients received a progesterone device and 2 mg of oestradiol benzoate on Day 0; device removal, prostaglandin F2α, and eCG on Day 6; gonadotropin-releasing hormone on Day 9; and FTET on Day 16. On the day of FTET all recipients with CL ≥18 mm in diameter (G1), ≥16 and <18 mm in diameter (G2), and ≥14 mm and <16 mm in diameter (G3) received in vitro-produced fresh embryos. Pregnancy was diagnosed by ultrasonography at 30 and 60 days of gestation, and data were analysed by logistic regression. The overall proportion of recipients synchronized that were FTET was 80.8% (1487/1841), with a 30-day pregnancy rate to FTET (P/FTET) of 45.6% (678/1487) and the rate of 30- to 60-day embryo/fetal loses on the 528 recipients that were re-checked at 60 days was 12.8% (68/528). There were no significant differences in P/FTET among operators, animal category, time of the year, embryo stage, or body condition score; however, there was a significant effect of farm (P < 0.001) and CL diameter (P < 0.05), but no interaction between CL diameter and farm or treatment (P > 0.1). Recipients with G1 (443/953, 46%) and G2 (221/462, 47%) CL had higher pregnancy rates than those with G3 CL (23/71, 32%). There was a significant effect of synchronization treatment on the proportion of recipients transferred and on P/FTET (P < 0.01) that was highly influenced by farm (farm by treatment interaction P < 0.01). The proportions of recipients selected for embryo transfer were as follows: T1: 386/486, 79.4%; T2: 233/331, 70.3%; T3: 342/377, 90.7%; T4: 126/160, 78.7%; and T5: 400/487, 82.1%. The P/FTET were as follows: T1: 190/386, 49.2%; T2: 96/233, 41.2%; T3: 175/342, 51.1%; T4: 49/126, 38.8%; and T5: 168/400, 42.0%. Although 30- to 60-day embryo/fetal losses were not influenced by synchronization treatments, they were highly influenced by farm (P < 0.001) and ranged from 0 to 34.5%. In conclusion, P/FTET in a commercial program with beef in vitro-produced embryos was influenced by factors related to the recipient (CL diameter) and the environment (farm), whereas embryo/fetal losses were influenced by farm but not treatment or recipient factors.
The objective of this study was to evaluate the effect of synchronization treatment and oestrus expression on conception rates and pregnancy losses in recipients receiving in vitro-produced (IVP) embryos. Crossbred beef cows (n = 407) with a corpus luteum (CL) determined by ultrasonography and body condition between 2.5 and 4.5 (1 to 5 scale) received a progesterone-releasing device (DIB 0.5 g, Zoetis, Argentina) and 2 mg of oestradiol benzoate (EB, Gonadiol, Zoetis) on Day 0 and were randomly allocated to 1 of 2 treatments. Recipients in the Conventional group (n = 201) had their devices removed and received 500 µg of cloprostenol (PGF, Ciclase, Zoetis), 0.5 mg of oestradiol cypionate (ECP, Cipiosyn, Zoetis), and 400 IU of eCG (Novormón, Zoetis) on Day 8. Recipients in the J-Synch group (n = 206) had their devices removed and received PGF and eCG on Day 6. All recipients were tail-painted at device removal to determine the presence of oestrus on Day 10 (a.m.) in the Conventional group and on Day 9 (a.m.) in the J-Synch group. All recipients not in oestrus in both groups received 100 µg of gonadorelin (GnRH, Ovurelin, Bayer, New Zealand) at that time. In addition, the paint was observed again in the p.m. and it was recorded. Recipients were examined by ultrasonography 7 days after oestrus or GnRH treatment (Day 16 in the J-Synch group and Day 17 in the Conventional group) and those with a CL = 16 mm in diameter received an IVP fresh embryo non-surgically. Pregnancy was determined by ultrasonography 23 and 53 days after embryo transfer and calving rates were recorded. Data were analysed using generalized linear models for binary data and a logit link (InfoStat, https://www.infostat.com.ar/). The proportion of recipients transferred was higher (P < 0.05) in the Conventional group (90.0%, 180/201) than in the J-Synch group (83.5%, 172/206). However, conception rates and the percentage of recipients pregnant/treated did not differ between groups (Conventional: 36.6%; 66/180 and 32.8%; 66/201 v. J-Synch: 39.0%; 67/172 and 32.5%; 67/206). Although no interaction was detected between treatments and oestrus expression, the conception rate was higher (P < 0.05) in recipients showing oestrus (39.1%, 124/317) than in those not showing oestrus (25.7%, 9/35). Furthermore, embryo/fetal losses between 30 and 60 days were not affected by the synchronization treatment (P > 0.11), but they were lower (P < 0.01) in recipients showing oestrus (5.6%, 7/124) than in those not showing oestrus (66.7%, 6/9). Similarly, fetal losses between 60 days and calving tended to be lower (P < 0.06) in recipients showing oestrus (20.5%, 24/117) than in those not showing oestrus (66.7%; 2/3). Calving rates were higher in recipients showing oestrus (29.3%, 93/317) than in those not showing oestrus (2.9%, 1/35; P < 0.01). In conclusion, although both synchronization treatments performed similarly, recipients not showing oestrus after progesterone device removal had lower conception rates and higher pregnancy losses than those showing oestrus at the expected time after treatment.
An experiment was designed to evaluate whether expression of oestrus in recipients synchronized with progesterone devices and oestradiol affects pregnancy rates to a fixed-time embryo transfer (FTET). A secondary objective was to determine whether administration of gonadotropin-releasing hormone (GnRH) to those recipients not showing oestrus by 48 h after device removal had an effect on pregnancy rates. Mature, non-lactating beef recipients (Bonsmara, Brangus, and Braford; n = 729), with a corpus luteum (CL) or a follicle ≥8 mm in diameter detected by ultrasonography (Mindray DP 30, Shenzhen, China) and body condition score 2 to 4 (1 to 5 scale) were synchronized in 7 replicates. On Day 0, recipients received a progesterone device (DIB 0.5 g, Zoetis, Buenos Aires, Argentina) and 2 mg of oestradiol benzoate (Gonadiol, Zoetis). On Day 8, DIB were removed and recipients received 400 IU eCG (Novormon 5000, Zoetis) plus 0.5 mg of oestradiol cypionate (Cipiosyn, Zoetis) and 500 μg of cloprostenol (Cyclase, Zoetis). In addition, all cows were tail-painted on the sacrococcygeal area (CeloTest, Biotay, Buenos Aires, Argentina) at DIB removal and were observed to determine the expression of oestrus, according to the percentage of paint loss 48 h later. The animals that showed oestrus (paint loss >30%) were recorded, and those with paint loss ≤30% (not in oestrus) were randomly allocated to receive 100 μg of gonadorelin (GnRH; Gonasyn, Zoetis) or no treatment. On Day 17, all recipients were examined by ultrasonography and those with a CL ≥18 mm (G1), ≥16 and <18 mm (G2), or ≥14 and <16 mm (G3) in diameter received in vivo-produced frozen-thawed embryos by direct transfer or fresh in vitro-produced embryos. Pregnancy was diagnosed by ultrasonography at 23 days after FTET, and data were analysed by logistic regression. There were no differences between replicates, in vivo- and in vitro-produced embryos, or operators (P > 0.2). However, the proportion of recipients transferred and pregnant (P/FTET) was higher (P < 0.05) for those that showed oestrus at 48 h after DIB removal (422/454, 93.0% and 227/471, 48.2%) than those that did not show oestrus (109/211, 51.7% and 45/120, 37.5%). Within the recipients not showing oestrus, P/FTET was significantly higher (P < 0.05) in those that received GnRH (34/74, 45.9%) than in those that did not receive GnRH (12/46, 26.1%). There was a significant interaction (P < 0.05) between CL diameter and expression of oestrus. When recipients had CL ≥18 mm in diameter (G1), P/FTET did not differ (oestrus: 164/338, 48.5% v. no oestrus 30/65, 46.2%); however, when CL diameter was <18 mm and ≥14 mm (G2 and G3), P/FTET was higher (P < 0.05) in those that showed oestrus (37/85, 43.5%) than in those that did not show oestrus (11/43, 25.6%). Finally, P/FTET was higher (P < 0.05) in recipients with a CL (268/573, 46.8%) on Day 0 than in those with follicles >8 mm in diameter (4/18, 22.2%). In conclusion, the expression of oestrus significantly affected the percentage of recipients selected for embryo transfer and P/FTET. Furthermore, treatment of recipients not showing oestrus by 48 h after DIB removal with GnRH at that time increased P/FTET.
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