Responsiveness of bovine corpora lutea to prostaglandin F2 alpha: comparison of corpora lutea anticipated to have short or normal lifespans

The objective of this study was to determine if corpora lutea anticipated to have short lifespans were more responsive to the luteolytic action of prostaglandin F2 alpha (PGF2 alpha) than corpora lutea anticipated to have normal lifespans. Sixteen cows were allotted randomly to a hysterectomized-control (HC) or hysterectomized-progestogen (norgestomet) implant (HN) group. To verify that progestogen treatment of postpartum cows prior to induction of ovulation with gonadotropin-releasing hormone (GnRH) results in an increased number of cows exhibiting normal-length luteal phases, 21 additional cows were allotted randomly to a uterine intact-control (IC) or a uterine intact-progestogen implant (IN) group. Cows allotted to the HN and IN groups received norgestomet ear implants for 9 d beginning 17 to 21 d postcalving. All cows were injected (i.m.) with 100 micrograms GnRH 28 to 32 d postcalving (48 h after implant removal in the HN and IN groups) to induce ovulation. Two or 3 d after GnRH injection (d 0), cows in the HC (n = 8) and HN (n = 8) groups were hysterectomized to remove the major endogenous source of PGF2 alpha, and on d 7 cows were injected (i.m.) with 10 mg PGF2 alpha to assess luteal sensitivity. The proportion of corpora lutea having normal lifespans was greater (P less than .1) for the IN than for the IC group. In HC and HN groups, concentration of progesterone (P) increased similarly from d 0 to 6. Injection of PGF2 alpha in HC and HN groups on d 7 decreased (P less than .01) concentration of P approximately 50% by 6 h after injection (similar for both groups). Complete luteolysis was induced by PGF2 alpha in none of eight and two of eight cows in the HC and HN groups, respectively. In remaining cows (HC and HN groups) concentration of P increased (P less than .01; similar for HC and HN groups) beginning 24 h after PGF2 alpha and remained elevated through d 30 to 34 (end of experimental-period). In summary, corpora lutea anticipated to be short-lived were not more responsive to PGF2 alpha than corpora lutea anticipated to have normal lifespans.     

Effects of uterus and prostaglandin F2alpha on corpora lutea in Mongolian gerbils and guinea pigs.

One or both uterine horns were removed on postpartum day 6 day 1=parturition in pseudopregnant gerbils. On dy 16, the corpora lutea (C) in unilaterally hysterectomized gerbils were smaller (P less than 0.05) in the ovary adjacent to an intact horn than in the ovary adjacent to a removed horn. The cL were smaller in uterine-intact than in completely hysterectomized gerbils. I n another experiment, the cl were smaller (P less than 0.05) in pseudopregnant gerbils given a single intrauterine injection of a 30- or 20-mug dose of prostaglandin F2alpha) (PGFalpha) on postpartum day 6 and theen necropsied on day 10 than in gerbils given 10-, 5-, 1-, and 0-mug doses; CL were smaller (P less than 0.05) on the side ipsilateral to the treated horn than on the opposite side, although the interaction of dose and side was not significant...     

Effects of prostaglandin f(2alpha) on corpora lutea formation and function in mated bitches

Fifteen mated bitches were used to study the effects of prostaglandin F_2α on ovarian endocrine function during the early and midluteal phase. Five dogs were kept as controls, five were given 250 μg/kg prostaglandin F_2α twice daily between the first and fifth day of metestrus, and five were similarly treated with prostaglandin F_2α between 31 and 35 days of metestrus. Function of corpora lutea was monitored by measuring serum progesterone concentrations during the first 45 days of gestation.

Dogs treated with prostaglandin F_2α during the early luteal phase had progesterone concentrations similar to controls and pregnancies were undisturbed in both groups. A dramatic decrease in serum progesterone concentration and abortion resulted after prostaglandin F_2α administration at midpregnancy.

These results indicate that prostaglandin F_2α was not luteolytic during the early luteal phase and was therefore ineffective for preventing pregnancy at that time. However, at the dosage and frequency used in this study, prostaglandin F_2α was luteolytic and abortifacient at midgestation.

     

Effect of human chorionic gonadotropin on induced ovine corpora lutea during the anestrous season

Experiments were conducted to determine the effect of additional gonadotropic support on induced corpora lutea of anestrous ewes. In one series of experiments, ewes were superovulated and half the ewes received an i.v. injection of 500 IU human chorionic gonadotropin (hCG) on day 5 after ovulation. Corpora lutea were collected from both groups on day 10 after ovulation. Dissociated corpora lutea collected from ewes which received additional hCG contained proportionately more large luteal cells than did those from control ewes (P<.05). In neither cell type was content of receptors for luteinizing hormone (LH) or secretion of progesterone in response to LH affected by an additional injection of hCG. Large cells from anestrous ewes produced more progesterone in response to LH (P<.05) than did large cells from similarly treated ewes during the breeding season. Small cells collected during either season responded similarly to LH. In another series of experiments, anestrous ewes were induced to ovulate and were exposed to fertile rams. Half the ewes received an i.v. injection of 500 IU hCG on day 5 after ovulation. Serum content of progesterone was higher on day 10 in ewes which received hCG 5 days earlier than in control ewes, although progesterone levels declined to generally nondetectable levels in nonpregnant ewes of both groups by day 16. Pregnancy rates in the two groups were not different. We concluded that additional gonadotropic support affects the morphology and function of corpora lutea from anestrous ewes and may be useful for enhancing fertility during the nonbreeding season.     

Characterization of ovine follicles destined to form subfunctional corpora lutea

A study was done to test whether ovulatory follicles destined to form subfunctional corpora lutea differed from normal ovulatory follicles in steroidogenic function. Twenty-five ewes were treated with prostaglandin F2 alpha on d 11 of the estrous cycle, then unilaterally ovariectomized before (n = 13) or after (n = 12) the surge of luteinizing hormone (LH) at the induced estrus to collect "control" follicles, which would have produced normal corpora lutea. In 15 ewes, the second ovary was removed 63 to 84 h later to collect "treated" follicles before (n = 7) or after (n = 8) the second expected surge of LH. Five ewes (control) were allowed to ovulate from the remaining ovary at first estrus and another five (treated) at the second estrus (3 to 4 d later). Treated ewes had lower serum progesterone than control ewes during the ensuing cycle (P less than .05). Treated follicles contained less estradiol in the theca (4.4 +/- .6 vs 10.0 +/- 2.5 ng; P less than .05), less androstenedione (.1 +/- .1 vs 1.0 +/- .2 ng) and estradiol (.5 +/- .1 vs 2.9 +/- 2.2 ng) in the granulosa (P less than .05) and less progesterone in the follicular fluid (.8 +/- .4 vs 3.3 +/- .8 ng; P less than .05) than control follicles, when removed before the surge of LH. Follicles removed after the surge of LH did not differ. In conclusion, ovulatory follicles with low steroidogenic function became corpora lutea that secreted lower-than-normal quantities of progesterone.     

Function of ovine corpora lutea after administration of luteinizing hormone-releasing hormone

Ewes were treated with an agonistic analog of luteinizing hormone-releasing hormone (LH-RH) during the luteal phase (d 10) of the estrous cycle. Function of natural and hormonally-induced corpora lutea (CL) was evaluated by measurements of progesterone in sera or luteal tissue. Synthesis and secretion of progesterone by natural CL were not chronically altered by LH-RH. Likewise, there was no in vitro effect of LH-RH on luteal function. When natural CL were surgically removed, newly formed CL functioned at a defective level. Hysterectomy shortly after ovulation did not significantly influence such luteal activity. Induction of ovulation by LH-RH during the follicular phase (d 16) in uterus-intact ewes was followed by normal profiles of luteal secretion of progesterone; serum concentrations of progesterone in animals that were hysterectomized increased in association with development of the CL, but then plateaued at a subnormal level. There were no differences in patterns of secretion of luteinizing hormone in response to LH-RH due to stage of the estrous cycle. Follicles stimulated to ovulate during the luteal phase contained low numbers of steroidogenically-deficient granulosal-lutein cells. These results indicate that: ovine CL are not sensitive to exogenous LH-RH; luteal dysfunction is a consequence of ovulation during the luteal phase, and the etiology of this abnormality appears to be linked with the developmental status of the ovulatory follicle; and CL that are formed from ovulation of a matured follicle begin to develop normally, but then function at a defective rate in the absence of the uterus.     

Effect of prostaglandin F2 alpha administration on early pregnancy in ewes

Two trials were conducted with ewes to determine the effects of prostaglandin F2 alpha (PGF) administration during the first week of gestation. In trial 1, ewes (n = 134) were checked for breeding activity once daily and half of them received 10 mg PGF im at either 0, 24, 48, 72, 96, 120 or 144 h after detection of a breeding mark. The other half served as uninjected controls. In trial 2, ewes (n = 153) were checked for breeding activity twice daily. Two-thirds of the ewes received 10 mg PGF at either 24, 36, 48, 60, 72, 84, 96, 108, 120 and 132 h following detection of a breeding mark. The other one-third of the ewes served as uninjected controls corresponding to treatment times of 24, 48, 72, 96 or 120 h. In trial 1, the percentage of ewes lambing as a result of first service decreased as time of administration of PGF increased. The first-service pregnancy rate was 87.5% for ewes given PGF at 0 h and 0% for ewes given PGF at 144 h. Fewer (P less than .05) ewes given PGF at 96, 120 or 144 h after first mating lambed than control ewes. Similarly in trial 2, fewer (P less than .05) ewes given PGF at 96, 108, 120 or 132 h after first mating lambed than did controls. The total number of ewes lambing as a result of the entire breeding season did not differ (P greater than .05) between treated and control ewes in trial 1 (88.2 vs 87.3%) or trial 2 (85.7 vs 83.3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prostaglandin F2 alpha on adrenal-produced steroid hormones in cows

Ovariectomized, nonlactating cows were treated with IM injections of either physiologic saline solution or prostaglandin F2 alpha. Plasma concentrations of cortisol increased significantly by 30 to 60 minutes after injection of prostaglandin F2 alpha, but there were no significant increases in plasma concentrations of estradiol, progesterone, or testosterone. After saline solution treatment, there were no increases in any of the hormones measured.     

Presence of multiple corpora lutea affects the luteolytic response to prostaglandin F2α in lactating dairy cows

Since the 1970s, luteolytic doses used for synchronizing estrus in dairy cattle have remained unchanged. This study aimed to evaluate the dose-response effect of prostaglandin F_2α (PGF_2α), which is used for synchronizing estrus, and subsequent fertility in cows with two or more corpora lutea (CL). The study population consisted of 1,683 cows with a single CL (1CL), 501 cows with multiple CL receiving a single dose of PGF_2α (2CL1), and 252 cows with multiple CL receiving a 1.5 × PGF_2α dose (2CL1.5). Cows with a single CL (n = 1,245) showed estrus significantly (P < 0.01) earlier (3.01 ± 1.23 days; mean ± SD) than cows with multiple CL (n = 287; 3.33 ± 1.69 days). Using 1CL cows as reference, the odds ratio (OR) for the estrus response in 2CL1 cows was 0.13 (P < 0.0001), whereas the ORs for estrus response and pregnancy of 2CL1.5 cows were 1.8 (P = 0.0001) and 1.7 (P = 0.001), respectively. Based on the results for only the 2CL1 cows, the OR for the estrus response was 0.7 (P = 0.01) for cows producing ≥ 45 kg of milk at treatment, compared to the remaining cows producing < 45 kg of milk. Our results showed that the presence of multiple CL reduced the estrus response to that induced by a single PGF_2α dose and milk production was inversely associated with this response, whereas an increased PGF_2α dose improved the estrus response. Therefore, an increase in the standard PGF_2α dose is recommended.     

Comparison of induced corpora lutea from prepuberal gilts and spontaneous corpora lutea from mature gilts: hydroxysteroid dehydrogenase activity

The activity of hydroxysteroid dehydrogenases was histochemically quantified in corpora lutea (CL) from prepuberal gilts induced to ovulate and mature gilts. Prepuberal (P) gilts, 120 to 130 d of age were induced to ovulate with 1,500 IU pregnant mare serum gonadotropin (PMSG) followed 72 h later by 500 IU human chorionic gonadotropin (hCG). Three P gilts and three mature (M) gilts each were ovariectomized on d 10, 14, 18, 22 and 26 (d 0 = day of hCG for P gilts and onset of estrus for M gilts). Gilts ovariectomized on d 14, 18, 22 and 26 were hysterectomized on d 6 to ensure luteal maintenance. At the time of ovariectomy, CL were frozen in liquid nitrogen and then stored at -80 C until analysis. Cryostat sections (12 microns) were histochemically analyzed for delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta OHSD), 17 alpha-hydroxysteroid dehydrogenase (17 alpha OHSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha OHSD). The intensity of staining (greater enzyme activity resulted in darker staining) was quantified using a Zeiss SF microscope integrated with a Zonax photometer, which measured the percentage of light transmitted through a given area (22,500 microns 2) of the tissue section. Data were subjected to analysis of variance using the general linear models procedure of Statistical Analysis System (SAS). The 3 beta OHSD activity did not change over days, but the mean activity (throughout all days) in the P gilts (32.6 +/- 1.8) tended (P less than .08) to be elevated above that of M gilts (27.9 +/- 1.7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of large palpable ovarian follicles on response to prostaglandin administration in dairy cows with corpora lutea

We examined the response to exogenous prostaglandin F2α in cattle with or without palpable structures believed to be ovarian follicles. All animals had ovarian structures diagnosed by palpation as corpora lutea. The cows were placed into two groups: those with follicles which were estimated by the palpators to be ≤13 mm diameter (n=60); and cows with no palpable follicles or with follicles <13 mm diameter (n=133). Comparisons of proportion in estrus within five days, days to estrus, and milk progesterone levels failed to show significant differences between the groups.     

Effect of prostaglandin F2 alpha on the fertility of dairy cows after calving

Three hundred and thirty-one dairy cows in six herds were used to study the effect of a single injection of 25 mg dinoprost, a prostaglandin F2 alpha derivative, administered eight days after calving on several indices of fertility. A detailed comparison was made between 113 treated cows and 113 control cows of the same parity, which had calved within seven days of each other on the same farm and had experienced the same degree of dystocia. In cows which had calved without assistance, the treatment reduced the mean interval between calving and first heat from 40 days to 37 days but increased the mean interval between calving and conception from 83 days to 85 days. In cows which had required assistance at calving, the treatment reduced the mean interval between calving and first heat from 44 days to 34 days and reduced the mean calving to conception interval from 86 days to 68 days. The cows which benefited most were those which had required assistance during their second, third or fourth calvings; their calving to conception intervals were shortened by 22.5 days. An average of 1.39 services was required to establish conception in the treated cows which calved unaided, with 70 per cent conceiving to the first service, compared with an average of 1.34 services per conception and a 72 per cent conception rate to first service for their untreated herdmates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal regulation of oxytocin-induced prostaglandin F(2alpha) secretion by the bovine and ovine uterus in vivo

In long-term ovariectomized ewes and cows, endometrial oxytocin receptors rest at relatively high levels but oxytocin is unable to induce prostaglandin F(2alpha) release. A series of studies were carried out to investigate the roles of physiological levels of progesterone and estradiol in "activating" these receptors in terms of permitting oxytocin-induced prostaglandin F(2alpha) release. In long-term ovariectomized cows, treatment with progesterone, but not estradiol, resulted in the induction of responsiveness to oxytocin. This responsiveness appeared within 2 d of progesterone treatment, reached a maximum by 6 d and was maintained to Day 18. In ovariectomized ewes, while estradiol treatment did induce temporary responsiveness to oxytocin after 3 d of treatment, treatment with progesterone was required to induce sustained responsiveness that appeared by Day 9 of treatment and was maintained to Day 12. Measurement of endometrial receptors for oxytocin revealed a significant decline in oxytocin receptors by Day 6 of progesterone treatment when responsiveness to oxytocin was maximal, demonstrating that receptor concentrations were not a limiting factor. The most likely mechanism by which progesterone treatment induces responsiveness to oxytocin may be through the up regulation of post receptor signaling pathways and/or enzymes involved in prostaglandin synthesis.