THE ESTROUS CYCLE

The majority of mammals become sexually-receptive (express estrus) and ovulate spontaneously at defined intervals. The female will only allow the male to mate during a restricted time coinciding with ovulation. Inefficiency of reproduction is attributable in part to prolonged periods of estrus; thus, the female might need to be bred several times to augment the chances of conception (eg., the mare and dog).

Differences in lengths of estrous cycles among species (Table 4-4) are determined primarily by duration of the luteal phase. Luteal phases of larger mammals are long compared to species of lesser body stature. Many small animals are subject to predation, and cannot afford the luxury of lengthy nonpregnant cycles (moreover, they are usually litter-bearing, have short gestations, abbreviated or no lactational anestrus, and their young attain puberty quickly). Extinction can quickly besiege those species with extended reproductive cycles (eg., rhinoceroses and elephants).

Stages. The estrous cycle can be divided into four stages: proestrus, estrus, metestrus, and diestrus. During proestrus the CL regresses (progesterone declines) and a preovulatory follicle undergoes its final growth phase (estradiol increases). Ovulation usually occurs during estrus (cows ovulate during metestrus). Proestrus and estrus comprise the follicular phase. Corpora lutea develop during metestrus and function at optimum during diestrus. Metestrus and diestrus make up the luteal phase.

Reproductive tract. Changes in contractility and development of the reproductive tract are regulated by cyclic alterations in secretory patterns of steroid hormones. The oviducts and uterus are motile under the influence of estradiol; progesterone has the opposite effect. The endometrium undergoes proliferation during the follicular phase in response to rising circulatory titers of estradiol. Progesterone causes endometrial glands to become branched and secretory (Figure 4-43). Estradiol primes the endometrial response to progesterone (expressed during the luteal phase) by stimulating synthesis of receptors for progesterone (which inhibits synthesis of receptors for estradiol). The cervix becomes dilated in the follicular phase and constricted in the luteal phase; correspondingly, cervical mucus is of either a watery or more dense consistency (Figure 4-44). Each of the noted changes in the reproductive tract of the female have relevance to gamete transport and pregnancy - topics discussed in the next chapter.

Because structural integrity of the endometrium requires steroidal support, regression of the CL (or ovariectomy) leads to atrophy. An ebb and flow of degeneration, growth, and remodeling of the endometrium occurs in all mammals (necrosis and sloughing are pronounced in menstrual animals).

The vagina also presents cyclic changes according to hormonal fluctuations. Epithelial cells exfoliated from the vaginal wall can be collected onto a swab, smeared onto a slide, and examined under the microscope; the presence of cornified cells is indicative of estrus (Figure 4-45). Keratinization of the mucosal lining helps to minimize irritation to the vagina during copulation. With a drop in circulatory estradiol, cornified epithelia is sloughed and the vaginal mucosa becomes very thin; phagocytic leukocytes can then readily migrate into the vaginal lumen (Table 4-5).

Cows sometimes exhibit a bloody vaginal discharge during estrus or metestrus; the bleeding originates from essentially intact uterine vessels - diapedesis or pseudomenstruation. Diapedesis also occurs in the proestrous bitch. In some species (eg., murine rodents), conspicuous uterine intraluminal water imbibition at estrus occurs without overt loss of blood cells. Vessels apparently become leaky in response to an acute elevation in circulatory estradiol. Diapedesis is not the result of hormonal withdrawal, and therefore from a mechanistic standpoint is not comparable to menstruation. Possible local mediators of diapedesis are histamine, catecholamines, and arachidonate metabolites. Eosinophils infiltrate the uterus in response to estradiol.

Synchronization of estrus. There are advantages of being able to synchronize the timing of estrus and ovulation in livestock. Synchronization techniques result in a uniform animal crop and labor can be concentrated at parturition. Furthermore, efficient use of an AI technician is maximized when animals are synchronized to estrus. Estrous synchronization technologies are costly, laborious, generally yield lower rates of conception than natural service, and require skill and specialized facilities. The decision to implement a new system of management should be made only after it is deemed feasible and will solve more problems than it creates.

Two basic approaches to synchronization of estrus and ovulation have evolved from an understanding of female reproductive endocrinology - progestin and prostaglandin. Progestins mimic the luteal phase. Estrus and ovulation follow removal of the progestational influence. Prostaglandin F2a causes luteal regression, thereby synchronizing the onset of a follicular phase.

The Syncro-Mate-B system (history) involved placing a norgestomet-releasing implant between the skin and cartilage of the ear of a cow for nine days. At the time of implant insertion, the cow was injected with estradiol valerate to induce endogenous uterine production of luteolysin - so when the implant is removed, there was no natural source of progesterone to prevent a prompt return to estrus. Animals can be either observed for estrus (Table 4-6) and bred 12 hours later or bred-by-appointment 48 hours following implant removal. Advantages of the Syncro-Mate-B system were that some anestrous animals respond and synchrony of estrus was tight (timed insemination is practical). The system was expensive and labor intensive (animals must be handled twice). It was approved for use in beef animals and dairy heifers. A new alternative for (intravaginal) progesterone delivery is the Eazi-Breed CIDR (controlled internal drug-releasing), which is inserted for 7 days; Lutalyse is given on Day 6.

Orally-active progestins (eg., melengestrol acetate or altrenogest) have been incorporated into livestock rations. Feeding progestins is effective for induction of estrus, but has not met with widespread application because of cost, unequal consumption, and poor synchrony following cessation. Ewes can be induced to estrus by treatment with progestin (eg., two weeks by vaginal sponge impregnated with MPA or flurogestone acetate) and PMSG (at pessary removal); however, because of low corporate profits, these products are no longer readily available in the US marketplace.

Naturally-occurring PGF2a as the tromethamine salt (Lutalyse, Upjohn; ProstaMate, Phoenix Scientific), and synthetic analogs of PGF2a such as cloprostenol (Estrumate, Haver), are sold for synchronization of estrus in nonlactating cattle (Figure 4-46) and horses. The cost of a single-injection prostaglandin program is less than that of a progestin system and not as laborious. Animals must be in diestrus to respond to PGF2a (the young CL is insensitive to treatment), return to estrus is somewhat variable (semen is wasted if breeding-by-appointment), and treatment of pregnant females can cause abortion. Porcine CL will not respond to PGF2a until about Day 12 of the estrous cycle. Gonadotropin-releasing hormone (to induce ovulation and CL formation) is being used in cattle in combination with PGF2a (eg., SelectSynch: GnRH + PGF2a [Day 7]; Ov/CoSynch: GnRH + PGF2a [Day 7] + GnRH [Day 9]).

(For additional information on bovine estrous synchronization see: http://www.selectsires.com/reproductive_solutions.aspx  http://www.uaex.edu/Other_Areas/publications/PDF/mp383.pdf http://beef.unl.edu/learning/estrussynch.shtml)