Early Regression Of Corpora Lutea Research Articles

77 Occurrence of early regression of corpora lutea in Dorper ewes subjected to a conventional superovulatory regimen

The early regression of corpora lutea (ERCL) is a functional alteration that occurs more often in animals subjected to multiple ovulation followed by embryo transfer (MOET) technique. Although it is mainly reported in goats, sheep are also susceptible to this disorder. The ERCL may compromise the quality and viability of embryos, and even embryonic recovery rate. Thus, the non-diffusion of the animal genetic material on a commercial scale increases costs, decreasing efficiency. This study aimed to assess the occurrence of ERCL in embryo donor ewes subjected to the MOET programs in different seasons. The research was carried out in a commercial herd in São Luís do Paraitinga city (23°22′S and 45°26′W), Brazil, over 4 years (2017–2020). Forty-four Dorper multiparous ewes aged between 3 and 9 years old and with body condition score (BCS) between 2 and 4.5 (1 to 5 scale) were used. Each ewe was used at least once for MOET and a maximum of 5 times, totalling 104 procedures. Regardless of the day of the oestrous cycle or anovulatory period (Day 0), ewes received a conventional superovulatory protocol consisting of an intravaginal device treatment with 0.33mg of progesterone (CIDR®, Zoetis). On Day 7, the device was replaced with a new one and ewes administered i.m. 0.24mg of sodium cloprostenol (Sincrocio®, Ourofino). The superovulatory treatment [256mg of FSH (Folltropin®, Vetoquinol)] started on Day 12 and consisted of decreasing doses (20, 20, 15, 15, 10, 10, 5, and 5%) administered intramuscularly (IM) every 12h for 4 days plus 200IU of equine chorionic gonadotrophin (eCG, Novormon®, Zoetis) at device removal on Day 14 and 0.1mg of gonadotrophin-releasing hormone (Fertagyl®, MSD) IM 1 day later (Day 15). Laparoscopic AI was performed twice on Day 16 using cooled semen. Five days after AI, ovaries were assessed by laparoscopy to check the presence and viability of corpora lutea (CL). Ewes that had avascular CL (pinkish to whitish colour) were classified as ERCL and embryo collection was not performed. The occurrence of ERCL in each season and category of BCS was checked by either chi-squared or Fisher test. Logistic regression was performed according to the incidence of ERCL in each category of age. Values of P<0.05 were considered as significant. From 104 procedures, ERCL was identified in 26 cases, totalling 25% of occurrence. The proportion of occurrence did not differ (P>0.05) among seasons: breeding (10/43: 23%), transition (10/36, 28%), or anoestrous (6/25, 24%). There was no difference in ERCL incidence in ewes presenting different BCS categories: lower/thin (2 to 2.5: 3/12, 25%); average/good (3 to 3.5: 15/66, 22%) and higher/fat (4 to 4.5: 8/26, 31%). Indeed, there was no association (P>0.05) between ERCL and age. In conclusion, a relevant occurrence of ERCL was detected in superovulated embryo donor ewes but this incidence was not associated with season, age, or BCS of Dorper ewes. These data highlight the importance of pharmacological measures to control ERCL in MOET protocols for commercial sheep herds.

Maintenance or regression of the corpus luteum during multiple decisive periods of bovinepregnancy

In ruminants, there are specific times during the estrous cycle or pregnancy when the corpus luteum (CL) may undergo regression. This review has attempted to summarize the physiological and cellular mechanisms involved in CL regression or maintenance during four distinct periods. The first period is near day 7 when animals that are ovulating after a period of low circulating progesterone (P4), such as first pubertal ovulation or first postpartum ovulation, are at risk of having a premature increase in Prostaglandin F2α (PGF) secreted from the uterus resulting in early CL regression and a short estrous cycle. The second period is when normal luteolysis occurs at day 18-25 of the cycle or when the CL is rescued by interferon-tau secreted by the elongating embryo. The uterine mechanisms that determine the timing of this luteolysis or the prevention of luteolysis have been generally defined. Induction and activation of endometrial E2 receptors result in induction of endometrial oxytocin receptors that can now be activated by normal pulses of oxytocin. Of particular importance is the observation that the primary mechanisms are only activated through local (ipsilateral) and not a systemic route due to transfer of PGF from the uterine vein to the ovarian artery. In addition at the CL level, studies are providing definition to the cellular and molecular mechanisms that are activated in response to uterine PGF pulses or pregnancy. The third period that is discussed occurs in the second month of pregnancy (day 28-60) when undefined mechanisms result in CL maintenance of an ipsilateral CL but regression of a contralateral (opposite side from pregnancy) CL. The final period that is discussed is regression of the CL just prior to parturition. Although, cortisol from the fetus appears to be the primary initiator of luteolysis, PGF seems to be the final signal that causes regression of the CL. Thus, in all four periods, regression of the CL is likely to be caused by the direct actions of PGF that is secreted from the uterus. The uterine mechanisms that result in secretion of PGF seem to be normally inhibited during the early luteal phase, making short luteal phases not a normal event, and are altered during early pregnancy (day 18-25) resulting in prevention of luteolysis. During much of pregnancy, the mechanisms that cause PGF secretion from the uterus in response to oxytocin are intact but luteolysis does not normally occur, perhaps due to lack of efficient utero-ovarian transfer of PGF.

New approaches to superovulation and embryo transfer in small ruminants

The present paper reviews the current state of knowledge in multiple ovulation and embryo transfer (MOET) technology in small ruminants, focusing on recently reported information. Major new findings are related to follicular wave patterns in small ruminants, the elucidation of follicular dominance and the integration of this information into ovarian superstimulatory treatment protocols. Follicular dynamics determine steroid and gonadotrophin secretion, follicular responses to FSH, ovulatory responses and embryo yield. Protocols that control follicular dominance have been designed to allow the initiation of superstimulation at the beginning of a follicular wave. New approaches consist of (1) synchronisation of ovulation for superstimulation during Wave 1 (i.e. Day 0 protocol), (2) pretreatment with a gonadotrophin-releasing hormone (GnRH) antagonist from 10 days prior to FSH treatment to avoid follicular dominance and (3) progesterone-oestradiol cotreatment to synchronise follicle wave emergence. These protocols provide a homogeneous pool of small follicles that are gonadotrophin responsive, enhancing the superovulatory response and embryo yield with a reduction in the incidence of unovulated follicles and early regression of corpora lutea. In addition, the rate of fertilisation failure has been reduced by using an inducer of ovulation (i.e. GnRH) associated with intrauterine insemination. In summary, the application of recently acquired knowledge has resulted in relevant improvements in MOET programmes in small ruminants.

Role of the uterus in early regression of corpora lutea induced by the ram effect in seasonally anoestrous Barbarine ewes.

The involvement of the uterus in early regression of corpora lutea induced by the ram effect was studied in seasonally anoestrous Barbarine ewes. In experiment 1, group I was only submitted to the male effect (control, n = 15) while group II (n = 14) was injected every 12 h with flunixin meglumine, a PGF2 alpha synthetase inhibitor (finadyne), from day 3 to day 6 (day 0: day of ram introduction). The preovulatory LH surge appeared at the same time (around 21 h after ram introduction) in both groups. Finadyne treatment significantly decreased 13-14-dihydro-15-keto-PGF2 alpha (PGFM) pulses (1.3 +/- 0.3 versus 0.4 +/- 0.2; P < 0.05), the number of short cycles (50 versus 14%, P < 0.05), and provided a single peak of oestrus, 15-16 days after the introduction of the rams, instead of between day 14 and day 23 (P < 0.01). In experiment 2, 17 hysterectomized ewes were allocated into two groups: group III (n = 8) was injected with oil and group IV (n = 9) received an intramuscular injection of 20 mg of progesterone immediately before introduction of rams. An additional group of intact ewes was used as control (group V, n = 9). Hysterectomy did not affect the ovulation response to the ram effect, but completely suppressed short cycles (0 versus 78%, P < 0.001). The preovulatory LH surge was delayed in hysterectomized females (36.0 +/- 14.1 versus 16.6 +/- 11.4 h; P < 0.004). Treatment with progesterone significantly (P < 0.01) increased the interval between introduction of rams and the preovulatory LH surge. In conclusion, suppression of short cycles by hysterectomy and an inhibitor of PGF2 alpha synthetase suggest that the uterus is essential for determining the lifespan of ram-induced corpora lutea and that premature release of PGF2 alpha is the cause of early luteal regression. The hypothesis that lower secretion of progesterone before D5 could be the initial cause of the premature induction of the luteolytic signal is discussed.

Plasma oestrogen and progesterone in relation to superovulation and egg recovery in the cow.

Pregnant mares serum gonadotrophin (PMSG) was used in combination with prostaglandin F2alpha or its analogues to induce superovulation in 25 heifers. Total unconjugated oestrogen and progesterone were determined in peripheral plasma of these superovulated animals, and the levels compared with those found during the normal oestrous cycle. A very high level of oestrogen was found between day 3 and 6 after superovulation, and it seems likely that large unovulated follicles were responsible for the excess steroid. Similarly, progesterone levels were raised in the superovulated animal presumably due to production by the numerous corpora lutea. In two heifers, in which overstimulation of follicular development had occurred, there were no ovulations in one of the animals while in the other animal there were 16 ovulations but early regression of corpora lutea was indicated. It is concluded that the poor recovery of eggs on day 6 after superovulation could have been due to deleterious effects of high levels of oestrogen on either the motility of the genital tract causing the premature transport of eggs, or the properties of the zona pellucida.

Influence of gonadotropic hormones on estradiol-induced corpus luteum regression in the ewe.

The injection of estradiol into the ewe after the middle of the estrous cycle resulted in early regression of corpora lutea (CL) (Hawk and Bolt, 1970). In contrast, estradiol administered in the early part of the estrous cycle caused extended luteal maintenance (Piper and Foote, 1968). Bolt, Kelley and Hawk (1970) noted that the injection of estradiol on day 3 caused the release of endogenous LH, as indicated by an increase in plasma LH concentrations similar to the LH peak observed at estrus (Niswender et al., 1968). This study was done to determine whether the luteal regression resulting from an injection of estradiol on day 10 could be prevented by administration of (1) exogenous gonadotropic hormones on day 3, (2) estradiol on day 3 when it will cause endogenous gonadotropin release, or (3) gonadotropic hormones on day 10 at the time the estradiol was administered. Eighty-four parous Rambouillet ewes of about 8 years of age and weighing approximately 55 kg were checked for estrus twice daily using vasectomized rams.