Sandy Johnson, extension beef specialist, Colby
As we go through each breeding season, questions arise about changes, intentional or otherwise, regarding various synchronization protocols. What if I gave X rather than Y, or did something on day W rather than day Z; will it matter? In order to understand how estrus synchronization works and the importance of what happens in each step, a basic understanding of the tools used and how they influence the components of the estrous cycle is needed.
In brief, any estrus synchronization protocol is based on 3 key elements. 1) Exogenous (outside) supplementation of progesterone to block heat; 2) induced ovulation of the largest follicle and/or initiation of a new follicular wave; and 3) removal of all progesterone sources, allowing cows to come into heat and ovulate.
The Tools:
Progesterone – Biological function is to inhibit estrus and ovulation and maintain pregnancy. Commercially available forms in the US – Melengesterol Acetate (MGA) an orally active synthetic progestin; intravaginal inserts containing progesterone (CIDR – controlled internal drug release).
Early attempts to synchronize estrus used some form of progesterone to artificially extend the luteal phase because it would block estrus. When progesterone is given for two to three weeks, any corpora lutea (CL-internal source of progesterone) present naturally regress and when exogenous (coming from outside) progesterone is removed, ovulation is no longer blocked, and as a result, females exhibit estrus. We still use this approach today but recognize that follicles that ovulate immediately after a long-term progestin treatment will have low fertility.
Prostaglandin F2α – (PG) – Biological function is to cause luteal regression in non-pregnant females. Commercially available products: estroPLAN, Estrumate, In-Synch, Lutalyse, Lutalyse HighCon, ProstaMate, SYNCSURE.
Key to understanding how the estrous cycle was controlled was learning that prostaglandin F2α released from the uterus was responsible for regression of the CL. Administration of prostaglandin between day 6 and 16 of the cycle (estrus=day 0) results in regression of the CL and estrus follows in 2 to 3 days.
Gonadotropin Releasing Hormone (GnRH) – Biological function is to control the release of Luteinizing Hormone (LH)- Commercially available products Cystorelin, Factrel, Fertagyl, OvaCyst, GONABreed.
The last tool that was incorporated into estrus synchronization was GnRH. During the normal estrous cycle, increasing concentrations of estradiol from the ovulatory follicle will signal the brain to produce large amounts of GnRH. This in turn increases the rate of release of Luteinizing Hormone (LH) resulting in a surge of LH release and ovulation of the follicle. During each 21-day estrous cycle, 2 to 3 waves of follicular growth occur. For synchronization of ovulation (not just estrus) to occur, the timing of the development of a follicular wave needs to be synchronized. Researchers learned that an injection of GnRH during the estrous cycle could either cause ovulation of the largest follicle and/or cause a new wave of follicles to grow so that timing of ovulation could be better controlled.
Most protocols are designed to work on cows in all phases of the estrous cycle. Those protocols that include some form of a progestin have the ability to induce cyclicity in peripubertal and anestrus females. The administration of a progestin mimics the rise in progesterone that naturally occurs in prepubertal heifers and in postpartum cows before the first normal estrous cycle.
Putting these pieces together, let’s consider the fixed-timed AI protocol referred to as the 7-day CO-Synch + CIDR protocol for use in cows and shown in Figure 1.
Overall, the first injection of GnRH on day 0 is administered with the intention of causing ovulation. However, only cows with a follicle mature enough (~ 8.5mm in diameter) will ovulate in response to the GnRH injection. Following ovulation, a corpus luteum (CL) will be formed. The CL is the natural source of progesterone in the cow, and as mentioned above, progesterone will keep cows from coming into heat. Since we do not know if the cow will ovulate in response to the first GnRH injection, we also provide an artificial source of progesterone to ensure no cows will come into heat during those 7 days. On day 7 we remove the artificial source of progesterone (the CIDR) and administer an injection of PG to cause luteal regression and remove the natural source of progesterone. Following progesterone removal, the largest follicle in the ovary of the cows will grow and most cows will come into heat. The final GnRH injection at AI is administered to guarantee an ovulation happens in all females, especially those that have yet to show signs of estrus.
At any given point in time, we would expect cows to be at different stages of the estrous cycle. To understand how estrus synchronization works we can consider them into 3 categories: 1) cows between day 0 (estrus) and 5 of the estrous cycle, 2) cows between day 6 and 16 of the cycle, and 3) cows between 17 and 21 days of the cycle. To be effective, a synchronization protocol needs to work on cows in all 3 categories. Not all cows would need the same treatment if we knew the stage of the cycle at the onset.
Day 0 – 5 cows -GnRH at CIDR insertion will have little effect. The CIDR may interfere with normal CL formation but is not a problem. By the time the CIDR is removed cows will have a CL between day 7 and 12 that should respond to PG. CIDR removal is stimulatory to ovulatory follicle growth and ovulation is no longer blocked by progesterone.
Day 6 to 16 cows -GnRH at CIDR insertion will ovulate a new follicle or cause follicle turnover in a majority of cows, but response does vary. The CIDR will keep any cow whose CL regresses before CIDR removal from coming in heat. Cows that still have a CL when the CIDR is removed will respond to PG and the CL will regress.
Day 17 – 21 cows – GnRH at CIDR insertion is most likely to ovulate a new follicle. Most of these cows will have their CL regress before the CIDR is removed but PG is still given at CIDR removal since we don’t know which cows do or don’t have CL. In all cases the removal of progesterone either endogenously (from within) from the CL or from a CIDR and the administration of PG sets the final steps in motion for growth of the ovulatory follicle and expression of estrus.
The 7-day CO-Synch + CIDR protocol is very commonly used and other protocols share many common characteristics. A wide range of protocols have been studied and additional protocols that fit a wider range of situations including those for use with natural service can be obtained here https://beefrepro.org/protocols/.
If this brief overview used too much jargon (fair criticism) or just inspired you to study further, Mike Smith, University of Missouri covered this topic more thoroughly at the 2014 Applied Reproductive Strategies in Beef Cattle meeting. You can access slides, audio, and proceedings from that presentation at https://beefrepro.org/arsbc-archive/2014-arsbc-archive/ .
The 2024 Applied Reproductive Strategies in Beef Cattle meeting will be in Athens, GA Sept. 4-5. More information about the meeting will be coming soon at https://beefrepro.org/arsbc/
