When doses of progestin used commercially are administered to synchronize the stage of the estrous cycle among bovine females, fertility is reduced compared with that of untreated controls. The reduced fertility that results from the use of progestin based estrus synchrony regimens is associated with the development of persistent ovarian follicles. Persistent ovarian follicles develop as a result of the greater frequency of LH pulses that occurs during the period of treatment with progestins. The greater release of LH pulses results in enhanced secretion of 17 beta-estradiol from persistent ovarian follicles. The greater frequency of LH release or the greater secretion of 17 beta-estradiol associated with development of persistent ovarian follicles probably contributes to the reduced fertility that occurs when progestins are used to synchronize stage of the estrous cycle.
Infertility and subfertility represent major problems in domestic animals and humans, and the majority of embryonic loss occurs during the first month of gestation that involves pregnancy recognition and conceptus implantation. The critical genes and physiological pathways in the endometrium that mediate pregnancy establishment and success are not well understood. In study one, predominantly Angus heifers were classified based on fertility using serial embryo transfer to select animals with intrinsic differences in pregnancy loss. In each of the four rounds, a single in vitro-produced, high-quality embryo was transferred into heifers on Day 7 postestrus and pregnancy was determined on Days 28 and 42 by ultrasound and then terminated. Heifers were classified based on pregnancy success as high fertile (HF), subfertile (SF), or infertile (IF). In study two, fertility-classified heifers were resynchronized and bred with semen from a single high-fertility bull. Blood samples were collected every other day from Days 0 to 36 postmating. Pregnancy rate was determined on Day 28 by ultrasound and was higher in HF (70.4%) than in heifers with low fertility (36.8%; SF and IF). Progesterone concentrations in serum during the first 20 days postestrus were not different in nonpregnant heifers and also not different in pregnant heifers among fertility groups. In study three, a single in vivo-produced embryo was transferred into fertility-classified heifers on Day 7 postestrus. The uteri were flushed on Day 14 to recover embryos, and endometrial biopsies were obtained from the ipsilateral uterine horn. Embryo recovery rate and conceptus length and area were not different among the heifer groups. RNA was sequenced from the Day 14 endometrial biopsies of pregnant HF, SF, and IF heifers (n = 5 per group) and analyzed by edgeR-robust analysis. There were 26 differentially expressed genes (DEGs) in the HF compared to SF endometrium, 12 DEGs for SF compared to IF endometrium, and three DEGs between the HF and IF endometrium. Several of the DEG-encoded proteins are involved in immune responses and are expressed in B cells. Results indicate that preimplantation conceptus survival and growth to Day 14 is not compromised in SF and IF heifers. Thus, the observed difference in capacity for pregnancy success in these fertility-classified heifers is manifest between Days 14 and 28 when pregnancy recognition signaling and conceptus elongation and implantation must occur for the establishment of pregnancy.
Three experiments were conducted with female cattle during the postpartum period and during the estrous cycle to examine the effects of diet-induced hyperlipidemia on lipoprotein-cholesterol and triglyceride (TG) metabolism, ovarian follicular dynamics, and incidence of postpartum luteal activity. Dietary-lipid effects were examined independently of metabolizable energy intake. Feeding a high-lipid (HL) diet (8% total lipid) for the first 3 wk of the puerperium (Experiment 1) increased (p less than 0.0001) the concentration of total cholesterol and high-density lipoprotein-cholesterol (HDL-CH), but not TG, within follicular fluid (FF) of estrogen-active (E-A) and inactive (E-I) follicles. Increases (1.4- to 1.7-fold) were similar in proportion to those observed in peripheral blood serum, but absolute concentrations were about 45% of that in serum. Greater than 95% of the cholesterol in FF was HDL-CH, with a greater (p less than 0.06) proportion of HDL-CH sequestered by E-A compared to E-I follicles. The HL diet increased (p less than 0.06) the number of medium-sized (3.1-9.9 mm) follicles present at ovariectomy 19-21 days postcalving and increased (p less than 0.03) concentrations of FF androstenedione in E-I follicles 5-fold. Granulosa cells from preovulatory follicles (Experiment 2) of heifers fed HL diets secreted 2.1- to 3.5-fold greater (p less than 0.03) quantities of pregnenolone and progesterone in vitro. Finally, feeding HL supplements to postpartum range cattle for 30 days increased (p less than 0.05) the incidence of ovarian luteal activity by 18% (Experiment 3). Shifts in lipid metabolic status modify reproductive potential in cattle, independently of dietary energy intake.
The aim of the present study was to elucidate the time course according to which changes in circulating concentrations of progesterone influence pulsatile secretion of LH and secretion of 17 beta-estradiol. Our working hypothesis was that changing the dose of progesterone would result in changes in frequency of LH pulses and secretion of 17 beta-estradiol within 72 h. Five days after behavioral estrus, thirty-three cows were randomly assigned to one of five groups: 1) control, no treatment (CONT, n = 5); 2) treatment with two progesterone-releasing intravaginal devices (PRIDs) for 11 days (2PRID, 5-6 ng/ml plasma progesterone, n = 7); 3) treatment with a 0.5 PRID for 11 days (0.5PRID, 1-2 ng/ml plasma progesterone, n = 7); 4) treatment with 2 PRIDs for 8 days followed by treatment with a 0.5 PRID for 3 days (2-0.5PRID, n = 7); and 5) treatment with a 0.5 PRID for 8 days followed by treatment with 2 PRIDs for 3 days (0.5-2PRID, n = 7). Cows subject to PRID treatments received injections of prostaglandin F2 alpha on Days 1 and 2 (Day 0 = day of initiation of PRID treatments, fifth day of the estrous cycle in CONT cows) to lyse the existing corpus luteum. Cows were bled for 12 h at 15-min intervals on Day 7.5 of the treatment period (twelfth day of the estrous cycle in CONT cows). The dose of progesterone was changed on Day 8 in cows that were assigned to the 2-0.5PRID and 0.5-2PRID groups, and blood collections continued an additional 72 h to characterize profiles of circulating concentrations of LH and 17 beta-estradiol. Cows treated with a 0.5 PRID had a greater (p < 0.05) number of LH pulses and higher (p < 0.05) concentrations of 17 beta-estradiol throughout the entire blood collection period than cows in the 2PRID and CONT groups. An increase in the number of LH pulses was detected within 6 h after the change from the high to the low dose of progesterone (2-0.5PRID), and frequency of LH pulses was similar to that of cows in the 0.5PRID group for the remainder of the period of blood collection. LH pulse frequency declined within 6 h after the shift from the low to the high dose of progesterone (0.5-2PRID) and was similar to that of cows in the 2PRID group by 12 h after the dose was changed. Within 6 h after the dose of progesterone was changed, circulating concentrations of 17 beta-estradiol increased (p < 0.05) in cows shifted from the high to low dose (2-0.5PRID) and declined (p < 0.05) after the dose of progesterone was changed from low to high (0.5-2PRID). We conclude that changing the circulating concentrations of progesterone concurrently affects frequency of pulsatile LH release and secretion of 17 beta-estradiol within 6-24 h.
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