Low peripheral progesterone and late embryonic/early fetal loss in suckled beef and lactating dairy cows.

Pregnancy failure during placentation in lactating dairy cows was associated with low concentrations of serum progesterone. Beef cows have greater serum progesterone and less pregnancy failure. Experiment 1 determined that reduction of serum progesterone affected late embryonic/early fetal loss in suckled beef cows.

Intrauterine infusion of BQ-610, an endothelin type A receptor antagonist, delays luteolysis in dairy heifers.

Three separate in vivo experiments were conducted to evaluate the putative role of endothelin-1 (ET-1) during luteal regression in heifers. In Experiment 1, a single intraluteal injection of 500 microg BQ-610 [(N,N-hexamethylene) carbamoyl-Leu-D-Trp (CHO)-D-Trp], a highly specific endothelin A (ETA) receptor antagonist, did not diminish the decline in plasma progesterone following a single exogenous injection of 25 mg prostaglandin F2 alpha (PGF2alpha) administered at midcycle of the estrous cycle. In Experiment 2, six intrauterine infusions of 500 microg BQ-610 given every 12 h on days 16-18 delayed spontaneous luteolysis, as evidenced by an extended elevation (P=0.

Relationship of fertility to ovarian follicular waves before breeding in dairy cows.

Cows with two waves of follicular growth during the estrous cycle yield follicles that are older and larger at ovulation compared with cows having three waves. The objectives of the current research were 1) to compare fertility in cows with two or three follicular waves and 2) to examine associations between luteal function, follicular development, and fertility after breeding. Follicular waves were monitored by ultrasonography during the estrous cycle before insemination in 106 dairy cows.

Dynamic in vivo changes in tissue inhibitors of metalloproteinases 1 and 2, and matrix metalloproteinases 2 and 9, during prostaglandin F(2alpha)-induced luteolysis in sheep.

Prostaglandin F(2alpha) (PGF(2alpha)) typically initiates a cascade of events that leads to the functional and structural demise of the corpus luteum. A sheep model was used in which a 1-h, systemic infusion of PGF(2alpha) (20 microg/min) is given at midcycle. Such an infusion mimics the onset of spontaneous luteolysis by causing a transient decrease in peripheral plasma progesterone, which reaches a nadir ( approximately 60% of controls) at 8 h but returns to control levels by 16-24 h.

Endothelin-1 mediates prostaglandin F(2alpha)-induced luteal regression in the ewe.

A diversified series of experiments was conducted to determine the potential role of endothelin-1 (ET-1) in ovine luteal function. Endothelin-1 inhibited basal and LH-stimulated progesterone production by dispersed ovine luteal cells during a 2-h incubation. This inhibition was removed when cells were preincubated with cyclo-D-Asp-Pro-D-Val-Leu-D-Trp (BQ123), a highly specific endothelin ET(A) receptor antagonist.

Inter-relationships between endothelin and prostaglandin F2alpha in corpus luteum function.

In cattle and other species, the corpus luteum plays a central role in the regulation of cyclicity and maintenance of pregnancy. In the absence of fertilization and implantation, the corpus luteum undergoes functional and morphological regression or luteolysis. Luteal regression is initiated in domestic ruminants by surges of prostaglandin F2alpha (PGF2alpha) from the uterus.

Intraovarian regulation of luteolysis.

The corpus luteum is a transient gland, which is only functional for 17-18 days in the cyclic cow or for up to 200 days in the pregnant cow. Regression of the corpus luteum is essential for normal cyclicity as it allows the development of a new ovulatory follicle, whereas prevention of luteolysis is necessary for the maintenance of pregnancy. Evidence acquired over the past three decades indicated that PGF2 alpha is the luteolytic hormone in ruminants.

Elevated lipoprotein lipids and gestational hormones in women with diet-treated gestational diabetes mellitus compared to healthy pregnant controls.

The objective of this study was to describe plasma and lipoprotein perturbations in gestational diabetes mellitus (GDM) compared to controls, and determine if alterations in lipids are related to gestational hormones and/or glucose control. Maternal HbA1c, free fatty acids (FFA), beta-estradiol, progesterone, prolactin, and plasma, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), HDL2 and HDL3 triglyceride (TG), cholesterol, and dietary intake were determined for women with diet-treated GDM and controls in a longitudinal design. Subjects (N = 25/group) were matched for age, race, and body-mass index (BMI).

Regulation of endothelin-1 expression in the bovine corpus luteum: elevation by prostaglandin F 2 alpha.

Prostaglandin F2alpha (PGF2alpha) has been recognized as the physiological luteolysin in ruminants and other species for more than three decades; however, the mechanisms involved in its action are poorly understood. We previously have shown that endothelin-1 (ET-1) mediates, at least in part, the action of PGF2alpha, and the current study examines the effect of PGF2alpha on the expression of ET-1 in bovine corpus luteum (CL). Endothelins (ETs) were extracted from CL, collected at various times of the estrous cycle, and highest levels were found during luteolysis.

Long chain polyunsaturated fatty acids and bovine luteal cell function.

Experiments were conducted to determine the effects of exogenous polyunsaturated fatty acids (PUFA) on the production of progesterone and prostanoids by dispersed bovine luteal cells and to characterize endogenous luteal fatty acids throughout the estrous cycle. The addition of eicosapentaenoic acid (20:5, n3) resulted in a dose-dependent reduction of progesterone production and an increase in production of prostaglandin (PG) F2 alpha (PGF2 alpha) (p < 0.05).

Luteotropic and luteolytic mechanisms in the bovine corpus luteum.

The function of the corpus luteum (CL) is a key element in many reproductive processes including ovulation, length of the estrous cycle, recognition of pregnancy and embryo survival in all mammalian species. The main function of the CL is to produce progesterone which acts on its tissues to prepare them for successful pregnancy. The CL is controlled by numerous biological compounds which provide luteotropic support during the estrous cycle and pregnancy and for inducing luteolysis at the end of the cycle The purpose of this paper is to review the mechansims responsible for controlling the endocrine function of this tissue in the bovine ovary.

Effect of endothelin-1 on bovine luteal cell function: role in prostaglandin F2alpha-induced antisteroidogenic action.

Endothelin-1 (ET-1) a vasoactive peptide, is synthesized and secreted by endothelial cells. In the bovine corpus luteum (CL), endothelial cells constitute a major proportion (53.5%) of total CL cells.

Bovine corpus luteum function after removal of granulosa cells from the preovulatory follicle.

Experiments were conducted to determine the effects of removing granulosa cells from bovine preovulatory follicles on subsequent corpus luteum (CL) function. Holstein heifers were assigned to three groups: untreated controls (n = 6), removal of granulosa cells (n = 9) and removal and return of granulosa cells (n = 7). Surgery was performed 18-24 hr after the onset of estrus and in all cases after the preovulatory luteinizing hormone (LH) surge.

Function and lifespan of corpora lutea in ewes treated with exogenous oxytocin.

Oxytocin was administered to Dorset and Shropshire ewes in one experiment and to Dorset ewes in a further 4 experiments. In Exp. 1, concentrations of plasma progesterone and lengths of the oestrous cycle in ewes given oxytocin subcutaneously twice a day on Days 0-3, 2-5, 4-7, 6-9, 8-11, 10-13, 12-15 or 14-17 were similar to those of control ewes.

Differential origin and control mechanisms in small and large bovine luteal cells.

Studies of the calcium requirement and the relationship of intracellular calcium to progesterone synthesis in highly purified preparations of bovine luteal cells reveal a remarkably close relationship between intracellular calcium levels and steroidogenesis. The differential responses of the two cell types, summarized in Table 2, are beginning to reveal how the two cell types may co-operate to produce both luteotrophic and luteolytic responses at different stages of the oestrous cycle and early pregnancy. The luteotrophic mechanisms in the small cells are fairly clear; in addition to the luteotrophic effects of LH and cAMP, activation of protein kinase C leads to increased progesterone synthesis.

Effect of histone H2A on progesterone production by bovine luteal cells.

Histone H2A competitively inhibits binding of GnRH to high affinity rat ovarian receptor sites and blocks gonadotropin-stimulated steroid and cAMP accumulation during culture of rat granulosal or luteal cells. The objective of our study was to examine the progesterone suppressive effects of histone H2A on bovine luteal cells. In the first study, luteal cells were treated at Time = 0 h with a partially purified preparation of bovine ovarian histone H2A (3 ng GnRH equivalents, 800 micrograms protein), equivalent amounts of GnRH (3 ng), or BSA (800 micrograms) and incubated for a total of 4 h.

Characteristics of an antigonadotrophic GnRH-like protein in the ovaries of diverse mammals.

A GnRH-like protein, detected with a receptor assay for GnRH in rat ovarian membranes, is present in ovarian extracts of the rat, human, cow and ewe at levels much higher than immunoreactive GnRH. This protein has been partly purified and characterized from bovine ovaries. Highest levels of this protein are found in granulosa cells, but substantial activity is present in luteal, thecal and stromal tissue.

Involvement of lipoxygenase products of arachidonic acid metabolism in bovine luteal function.

A series of experiments was conducted to determine the effects of lipoxygenase products of arachidonic acid (AA) metabolism on the function of the bovine corpus luteum (CL). In the first experiment, reaction products of soybean lipoxidase-AA were added to dispersed bovine luteal cells in increasing concentrations. These lipoxygenase products resulted in a dose-related reduction in the biosynthesis of progesterone and 6-keto-prostaglandin (PG)F1 alpha, while the synthesis of PGF2 alpha was unaffected.

Role of luteal prostaglandins in the control of bovine corpus luteum functions.

Current and emerging concepts on regulation of bovine corpus luteum function by various metabolites of arachidonic acid are reviewed. A series of experiments are presented which support the concept that prostacyclin (PGI2), a metabolite of arachidonic acid via the cyclooxygenase pathway, plays a luteotropic role, and that products of the lipoxygenase pathway of arachidonic acid metabolism, particularly 5-hydroxyeicosatetraenoic acid (5-HETE), play a luteolytic role in the function of the bovine corpus luteum (CL). These ideas are supported by the following findings: injection of PGI2 directly into CL at mid-cycle produced a prolonged increase in peripheral plasma concentrations of progesterone; PGI2 stimulated synthesis of progesterone by dispersed luteal cells; synthesis of PGI2 by luteal cells was greatest during the period of early CL development (d 5 and 10), and diminished as the CL aged unless pregnancy ensued, causing a maintenance of the CL and synthesis of PGI2; administration of indomethacin, a blocker of synthesis of prostaglandin by the cyclooxygenase pathway, twice daily on d 4 to 6 of the estrous cycle inhibited CL development and caused a reduction in cycle length, suggesting the presence of a luteotropic prostaglandin; oxytocin administration twice daily on d 4 through 6 inhibited CL development and was accompanied by a 50% reduction in luteal synthesis of PGI2 by CL collected on d 7; large quantities of 5-HETE were found in luteal tissue; the addition of 5-HETE to dispersed luteal cells inhibited synthesis of progesterone and PGI2, while production of PGF2 alpha was unaffected.

Inhibition of bovine luteal function by indomethacin.

Experiments were conducted to determine the effects of infusing indomethacin, a prostaglandin synthetase inhibitor, into the uterine lumen on the development and function of the bovine corpus luteum in the presence and absence of concurrently administered oxytocin. Each treatment was given twice daily on d 4, 5 and 6 of the estrous cycle. Treatments (six heifers/group) and resulting estrous cycle lengths were as follows: (1) untreated controls, 20.

Prolongation of the bovine estrous cycle with a gonadotropin-releasing hormone analog.

A series of in vitro and in vivo experiments was conducted to determine the effects of gonadotropin-releasing hormone (GnRH) on bovine luteal function. Biosynthesis of progesterone by bovine luteal cells during a 2-h incubation was determined following addition of 0, 10, 20, 40, 80 and 100 ng GnRH. Synthesis of progesterone was significantly depressed only by the 100-ng dose of GnRH.

Effect of flunixin meglumine on prostacyclin accumulation in the equine eye.

A study was performed to identify prostacyclin (PGI2) in equine aqueous humor, demonstrate an increase in PGI2 following anterior chamber paracentesis, and determine the effects of subconjunctival injection of flunixin meglumine on PGI2 accumulation. Twenty ponies were found to be normal upon ocular examination and were placed under general anesthesia. Anterior chamber paracentesis was performed in both eyes (right and left); immediately afterward, 25 mg of flunixin meglumine was injected (subconjunctivally) in the left eye.

Prostacyclin, prostaglandin F2 alpha and progesterone production by bovine luteal cells during the estrous cycle.

Corpora lutea (CL) were collected from Holstein heifers on Days 5, 10, 15 and 18 (5/day) of the estrous cycle. Dispersed luteal cell preparations were made and 10(6) viable luteal cells were incubated with bovine luteinizing hormone (LH) and different amounts of arachidonic acid in the presence and absence of the prostaglandin (PG) synthetase inhibitor indomethacin. The concentrations of progesterone, PGF2 alpha and 6-keto-PGF1 alpha, the stable inactive metabolite of prostacyclin (PGI2), were measured.

Methylation in bovine luteal cells as a regulator of luteinizing hormone action.

Experiments were conducted to determine if methylation is a part of the mechanism by which luteinizing hormone (LH) and epinephrine stimulate progesterone production by dispersed bovine luteal cells. Corpora lutea (CL) were collected from 24 Holstein heifers on Day 10 of the estrous cycle and dispersed with collagenase. Net progesterone accumulation, representing total progesterone synthesized by 10(6) cells during a 2-h incubation was determined.

On the negative feedback regulation of gonadotropins in castrate and intact cattle with comparison of two FSH radioimmunoassays.

Two homologous radioimmunoassays for bovine follicle stimulating hormone (bFSH) were utilized in comparing the differential regulation of FSH and luteinizing hormone (LH) in response to ovariectomy or administration of gonadal steroids in cattle. There appeared to be significant LH cross-reactivity in one of the bFSH systems (bFSH-HS-2-17), but not in the other (bFSH-BP3). Concentrations of FSH in plasma measured by these two systems suggested both qualitative and quantitative differences.