Estrous Cycle & Estrus Sychronizaton

Learning Objectives

To understand the different parts of the estrous cycle. To understand the hormonal changes during the estrous cycle. To understand how the estrous cycle coordinates the events of female reproduction so it can be successful.

Anestrus Female is not cycling (No expression of heat over time) Cow has a 21 Day Estrous Cycle: Day 0 first Day of Standing Heat Proestrus Day 17­20 (Follicular Phase) Prior to estrus, CL is undergoing regression, progesterone levels fall below 1 ng/mL which allows final follicular development Tertiary follicle(s) and oocytes undergo final maturation Estrogen levels ­ One dominant follicle ­ Graafian Stage Stimulated to final maturation by FSH and LH Female starts to become receptive ­ Estrogen Estrogen prepares uterus and oviducts for sperm transport and fertilization ­ Smooth muscle contractions and cilia movement Estrogen initiates uterine changes for later embryo development Uterine glands and oviduct secretion

ESTRUS

Picture provided by Dr. Robert P. Wettemann

Estrus ­ Day of Standing heat! Day 0 of estrous cycle Lasts 12 to 20 hours in cow Female in heat High estrogens cause LH surge Estrogen from the Graafian follicle stimulate increase in GnRH which stimulates increase in LH LH surge causes ovulation GnRH increases to cause a large increase in LH (surge release) Ovulation occurs during estrus in ewe, sow and mare but metestrus in cow LH surge initiates corpus luteum formation Following ovulation ­ LH stimulates development of luteal cells from the granulosa and thecal cells of the ovulated follicle wall. Theca and granulosa cells luteinize by LH stimulation to differentiate in luteal cells

Metestrus

Day 2­4 of Estrous Cycle

In cow, ovulation occurs after the end of estrus Estrogen levels have decreased Graafian follicle has ovulated Corpus luteum is forming Developing from Corpus Hemorrhagicum Progesterone levels start to ­ Second increase in FSH occurs to stimulate another wave of follicular development Progesterone begins preparing the uterus for the embryo Embryo partially develops in the oviduct and moves into the uterus Moves into uterus on Day 4 ­ 5 depending on species

Diestrus

Day 5 ­ 17 of Estrous Cycle

Maximum corpus luteum size Mature at Day 12 of estrous cycle High progesterone levels inhibit final follicular development, ovulation and estrus Inhibits final maturation of follicle and estrus Negative feedback on GnRH Embryo continues to develop in the uterus Embryo signals the uterus it is present ­ no CL regression If embryo is not present ­ uterus releases PGF2α to cause CL regression If CL regresses, progesterone in blood decreases and Graafian follicle(s) begin final development that occurs in proestrus for ovulation at estrus. Estrous Cycle starts over!!!!

Hormonal Profiles During the Estrous Cycle

ng = nanogram 10­9 grams LH, FSH, Progesterone pg = picogram 10­12 grams Estrogen, PGF2α

When progesterone is less than 1 ng/ml it usually means the cow has regressed the CL and is coming into heat during the estrous cycle

Second Follicular Wave

Follicle will become atretic and regress as a new follicle grows to ovulate with CL regression

First Follicular Wave

Increases for CL regression

Second increase of FSH for follicle development. Inhibin is low as is progesterone

LH surge for ovulation

Estrus

Mare

Estrus

Estrus Adapted from Ginther, O.J. 1992. 2nd Edition Reproductive Biology of the Mare. p288

Phases of the Estrous Cycle Follicular Phase of the female estrous cycle when she is under estrogen stimulation Proestrus and Estrus Luteal Phase of the female estrous cycle when she is under progesterone stimulation Metestrus and Diestrus

Species Variation in Estrous Cycle Characteristics Estrous Cycle

EWE

SOW

COW

MARE

Length of Estrous Cycle

14 ­ 19 Days

18 ­ 22 Days

18 ­ 24 Days

16 ­ 24 Days

Length of Estrus

24 ­ 36 hours

48 ­ 72 hours

12 ­ 19 hours

2 ­ 11 Days

Time of Ovulation

24 ­ 36 hours After the onset of estrus

35 ­ 45 hours After the onset of estrus

10 ­ 11 hours After the end of estrus

1 ­ 2 Days Before the end of estrus

12 ­ 18 hours After the onset of estrus

16 ­ 14 hours After the onset of estrus and again 8 ­ 24 hours later

7 ­ 18 hours After onset of estrus

Second day and every other day in estrus

Time of AI

Learning Objective

To understand how estrus synchronization works and how to use it successfully.

Estrus synchronization: Why 1. Group females for parturition: a. Labor, Calving period Reduce calving season b. More uniform weaning weights. 2. Reduce time required for estrus detection. 3. Eliminate estrus detection with timed insemination: Hopefully in future, not always most efficient!!!

Cattle: Prostaglandins: PGF2α

Half­life in blood Lutalyse ­ Natural compound 25 mg dose I.M. 2­3 min Estrumate ­ Analogue 500 µg dose I.M. Prosolvin ­ Analogue 15 mg dose I.M. Bovilene ­ Analogue 1 mg dose s.q. Equimate ­ Analogue used in Mare

3­4 hrs 2 hrs 18­24 hrs

Principle ­ Regress active corpus luteum PGF2α is not effective between Day 0 ­ 4 of Estrous Cycle Regresses Day 5­17 corpus luteum. In estrus 2­5 days after injection heifers ~50 hours cows ~72 hours ~60­65% of herd should respond to injection. To single one time injection To get whole herd synchronized, give 2nd injection 11 days after 1st Cows responding to 1st injection have day 6­9 corpora lutea 11 Days following 1st injection Cows which did not respond to 1st injection now have day 6­17 corpora lutea Therefore, all cows now have a CL which will respond to PGF2α on day 11

Reasons for variation of response. Young and old corpora lutea may respond different Older CL have a larger mass Day 6­9 CL in heat within 40­50 hrs Day 10 ­16 CL in heat within 60­72hrs Heifers react sooner than cows Difference in body weight Can adjust dosage based on body weight for larger breeds ­ standard dose Lutalyse 25 mg/1100 lbs give additional 5 mg/500 lbs over 1100 lbs Animal may be pregnant ­ Abortion Females do not have a corpora luteum, i.e. are anestrus

Brahman cattle respond poorly to the two injection system of PGF2α Recommended: Inject and breed all responders Inject 2nd treatment 11 days later to all those not bred to 1st injection and breed on estrus detection

Management Consideration: Have proper facilities to handle animals Good reproductive records Have enough A.I. technician help One technician/100 cows will cause problems Should be around 30­50 cows/technician Be sure cows & heifers cycling Anestrus cows don’t respond to PGF2α No CL!!!!!! Use good fertility semen

Breeding with prostaglandins:

1. Breed 80 hours after 2nd injection

Conception Rate 31 ­ 80 %

Timed AI ­ variation in response over 2­5 days 2. Breed based on estrus after PGF2α

67%

3. Control cows bred based on estrus

75%

Based on estrus ­ Breed 12 hours after the 1st observed estrus activity AM/PM rule ­ Twice daily heat detection

Improving ovulation synchronization 48 hours after PGF2α ­Give GnRH Cystorelin (GnRH Analogue) Cause LH surge; achieved slight increase in conception rates Maybe a better quality CL. Improve conception rate 3­4% Used mostly in problem breeding cows

Use of progestogens for Estrus synchronization Principle: Maintain the cow under the influence of progesterone until corpus luteum regresses, remove progesterone ­ animal respond to progesterone with estrus 2­5 days later. Administration: Injection Time Consuming Feed

Mix in ration

Implant

Place in ear

Place in Pessary or Control Internal Drug Release (CIDR) Vagina

Synchromate B system: Day 1

Inject 5 mg estradiol valerate & 3 mg norgestomet Implant Norgestomet (Progestagen) 6 mg

Injection allows for rapid increase in progestin in blood while the implant initiates its release over several hours Remove implant 9 days later Rapid decrease in progestin in blood allows animal to return to heat 2 to 3 days Breed 48 to 60 hours later or 54 hours later If you use timed AI at 54 hours Better to heat check and breed Estradiol ­ Luteolytic to d 3­9 corpora lutea Norgestomet ­ Inhibits early C.L. development Therefore treatment blocks proestrus,estrus and early CL development. Wait 9 days for diestrus cows to regress CL

Sychromate B System can be used on noncycling cows which may induce them to come into heat. System is not dependent on having a CL as with the prostaglandin system. However, cows need to be in good condition and close to cycling to respond

Brahman cattle recommend to implant norgestomet No Injection ­ Estradiol causes a problem Inject PGF2α on Day 8 and pull implant on Day 9

Melengesterol Acetate (MGA) System

Feed progestogen for 9 days

(0.5 mg/head/day)

Prevents estrus in diestrus and proestrus animals Give PGF2α on Day 8 to regress C.L.'s Remove progestogen on Day 9 Cows are in heat in 2­5 days Alternative Feed MGA for 14 days ­ Don’t breed on first heat (poor fertility) Inject PGF2α 16 days after withdrawal of MGA and breed on estrus detection

EAZI-BREED CIDR System

Insert CIDR (progestin) with CIDIROL capsule (estrogen) in vagina Day 6 inject with PGF2α Remove CIDR Day 7 and breed on heat detection Can inject with CIDIROL on Day 8 and breed by timed insemination 50 hours from CIDR removal

EAZI-BREED CIDR Beef Cow

Day 6

Day 7

Day 8

Day 9-11

7 Days Insert CIDR Inject PG Remove Inject Detect Estrus with CIDIROL CIDR 2mL or capsule CIDIROL Inseminate Fixed-time 50 hours

Ewe estrus synchronization: Implant progestogen for 12­14 days Use 1/2 of a new norgestomet implant Remove implant, ewes in heat in 36­60 hours May use PMSG at implant removal to stimulate follicular growth 400 ­ 800 IU Fertility good 1 ram/10 ewes Procedure will also work with CIDR and Pessary (Vaginal Sponge Can use PGF2α if during the breeding season Give 20 mg Lutalyse 9 days apart ­ No Effect If Anestrus

Sow estrus synchronization: PGF2α will not cause C.L. regression until day 12 of the cycle Reason ­ LH binds to luteal cell receptor with strong affinity following ovulation and is not released until day 12 Repeated injections over two to three days will regress CL before Day 12 but is not practical Common progestogens will synchronize estrus but cause ovarian cysts Progestogen ­ In Horse tradename Regumate is effective Allyl trenobolone fed at 20 mg/head/day for 18 days ­ remove from feed ­ in heat in 4­8 days. Fertility normal ­ a minor incidence of cysts.

Prepubertal gilts (noncycling) can be effectively synchronized with P.G. 600 P.G. 600 400 IU PMSG (eCG) and 200 IU HCG Gilts cannot be cycling Need to be greater than 51/2 months of age Gilts should express heat 3­4 days following treatment

Mare estrus synchronization: Luteolytic PGF2α in diestrus, in heat in 4­5 days Will only work during diestrus when CL is present Remember heat is over 5­11 days Use of prostaglandins in horses: Equimate (Fluprosterol) Give 250 µg ~1/5 cow dose

If you use Lutalyse or Estrumate

Mare CL more sensitive than cow, ewe Problems with smooth muscle stimulating properties of PGF2α which occur within 15 mins

Side Effects: 1. Sweating in neck, shoulders and central abdominal region 2. Increase Heart rate and Respiration 3. Increase motility of GI Tract (Colic) These should disappear within 1 hour Treatments with PGF2α Mares can exhibit what is called Prolonged Diestrus Caused by persistent luteal function ­ CL form after ovulation fails to undergo luteolysis during normal diestrus ­ remains 3­4 weeks ­CL maybe deep ­ unable to produce enough progesterone for stimulation of endometrial PGF2α release or caused by low grade uterine infection Failure of embryo to survive but extended CL lifespan as in normal pregnancy Equimate can be used to induce estrus when mares arrive to be bred by a stud

Use of progestins in horses Regumate

Can inject progesterone daily 150­200 mg i.m.

.044 mg/Kg body weight in feed Liquid Regumate 1 mL/110lbs Feed for 12 days or 15 days without equimate injection Remove from feed; give equimate In heat 3­4 days later Remember will not ovulate until day 8 of estrus Utilization: 1. Can use on show mares to suppress heat during events 2. Transport mare to breeding farm to time estrus 3. Regulate number of mares in heat to utilize a stallion over time. Synchronize mating