Egg Transport

February 20th, 2005

The oocyte, at the time of ovulation, is surrounded by granulosa cells (the cumulus oophorus) that attach the oocyte to the wall of the follicle. The zona pellucida, a noncellular porous layer of glycoproteins, separates the oocyte from the granulosa cells. The granulosa cells communicate metabolically with the oocyte by means of gap junctions between the oocyte plasma membrane and the cumulus cells. In response to the midcycle surge in luteinizing hormone (LH), maturation of the oocyte proceeds with the resumption of meiosis as the oocyte enters into the second meotic division and arrests in the second metaphase. Just before ovulation, the cumulus cells retract their cellular contacts from the oocyte. The disruption of the gap junctions induces maturation and migration of the cortical granules to the outer cortex of the oocyte. Prior to ovulation, the oocyte and its cumulus mass of cells prepare to leave their long residence in the ovary by becoming detached from the follicular wall.
Egg transport encompasses the period of time from ovulation to the entry of the egg into the uterus. The egg can be fertilized only during the early stages of its sojourn in the fallopian tube. Within 2-3 minutes of ovulation, the cumulus and oocyte are in the ampulla of the fallopian tube.

In rats and mice the ovary and distal portion of the tube are covered by a common fluid-filled sac. Ovulated eggs are carried by fluid currents to the fimbriated end of the tube. By contrast, in primates, contain humans, the ovulated eggs adhere with their cumulus mass of follicular cells to the surface of the ovary. The fimbriated end of the tube sweeps over the ovary in order to pick up the egg. Entry into the tube is facilitated by muscular movements that bring the fimbriae into contact with the surface of the ovary. Variations in this pattern surely exist, as evidenced by women who achieve pregnancy despite having only one ovary and a single tube located on the contralateral side. Furtherany more, eggs deposited in the cul-de-sac by transvaginal injection are picked up by the tubes.

Although there can be a little negative pressure in the tube in association with muscle contractions, ovum pickup is not dependent upon a suction effect secondary to this negative pressure. Ligation of the tube just proximal to the fimbriae does not interfere with pickup. The cilia on the surface of the fimbriae have adhesive sites, and these seem to have prime responsibility for the initial movement of the egg into the tube. This movement is dependent upon the presence of follicular cumulus cells surrounding the egg, because removal of these cells prior to egg pickup prevents effectual egg transport.
In the ampulla of the tube the cilia beat in the direction of the uterus. In women and monkeys this unidirectional beat is also found in the isthmus of the tube, whereas in the rabbit there are additional rows of cilia that beat in the direction of the ovary. The specific contribution of the cilia to egg transport in the ampulla and isthmus is an unresolved question. Most investigators have credited muscular contractions of the tubes as the primary force for moving the egg. However, interference with muscle contractility in the rabbit did not block egg transport. Reversing a segment of the ampulla of the tube so that the cilia in this segment beat toward the ovary interferes with pregnancy in the rabbit without blocking fertilization. The fertilized ova are arrested when they come in contact with the transposed area. This again suggests that ciliary beat is crucial for egg transport. Cilia play, in all likelihood, a less important role in the human. There are fertile women who have Kartagener's syndrome in which there is a congenital absence of dynein arms in cilia, and thus the cilia do not beat. This deficiency in the cilia is found in the fallopian tubes as well as in the respiratory tract.

Muscular contractions of the tube are associated with a to-and-fro movement of the eggs rather than with a continuous forward progression. In most species transport of the ovum through the tube requires approximately 3 days. The time spent within the various parts of the tube varies from one species to another. Transport through the ampulla is rapid in the rabbit, whereas in women it requires 30 hours for the egg to reach the ampullaryisthmic junction. The egg remains at this point another 30 hours, at which time it begins rapid transport through the isthmus of the tube.

Attempts to modify tubal function as a method for understanding its physiology have involved three major pharmacologic approaches: 1) altering levels of steroid hormones, 2) interference with or supplementation of adrenergic stimuli, and 3) treatment with prostaglandins. Although there is abundant literature on the effects of estrogen and progesterone on tubal function, it is clouded by the use of different hormones, different doses, and different timing of injections. Because of these variations it is difficult to obtain a coherent picture and to relate the experimental results to the in vivo situation. In general, pharmacologic doses of estrogen favor retention of eggs in the tube. This "tube locking" effect of estrogen can be partially reversed by treatment with progesterone.
The isthmus of the tube has an extensive adrenergic innervation. Surgical denervation of the tube, however, does not disrupt ovum transport. Prostaglandins (PG) of the E series relax tubal muscle, whereas those of the F series stimulate muscle activity of the tube. Although PGF2a stimulates human oviductal motility in vivo, it does not cause acceleration of ovum transport.
The effect on fertility of removal of different segments of the tube has been reviewed by Pauerstein and Eddy, who noted that excision of the ampullary-isthmic junction in rabbits did not block fertility. This is equally true if little segments of the ampulla are removed, and pregnancy can occur even if the entire isthmus and uterotubal junction are excised. Although the fimbriae are thought to play a crucial role in fertility, spontaneous pregnancies have been reported follittleing sterilization by fimbriectomy or follittleing surgical repair of tubes whose fimbriated ends had been excised. 33

In most species, a period of residence in the tube appears to be a prerequisite for full development. Rabbit eggs can be fertilized in the uterus, but they do not develop unless transferred to the tubes within 3 hours of fertilization. This and other work implies that there may be a component in uterine fluid during the first 48 hours follittleing ovulation that is toxic to the egg. Indirect evidence of an inhospitable environment is also provided by studies indicating that there must be synchrony between development of the endometrium and the egg for successful pregnancy to occur. ?-?+ If the endometrium is in a any more advanced stage of development than the egg, fertility is compromised. Thus, it is conceptually useful to view the fallopian tube not as an active transport mechanism, but as a structure that provides an important holding action. This functional behavior is coordinated by the changing estrogen and progesterone levels after ovulation.

Successful pregnancies have occurred in the human follittleing the Estes procedure, in which the ovary is transposed to the uterine cornua. Eggs are ovulated directly into the uterus, completely bypassing the tube. Moreover, when fertilized donor eggs are transferred to women who are on hormone supplementation, there are a number of days during the treatment cycle when the blastocysts will implant. This crucial difference between animal and human physiology is of any more than academic importance. There has been speculation concerning the use of drugs that could accelerate tubal transport as a means of providing contraception by ensuring that the egg would reach the uterus when it was in an unreceptive state. Although this may work in animals, it is of doubtful value in the human because perfect synchrony is not required.

Animal and human reproduction also differ in the occurrence of ectopic pregnancy. Ectopic pregnancies are rare in animals, and in rodents they are not induced even if the uterotubal junction is occluded immediately follittleing fertilization. The embryos reach the blastocyst stage and then degenerate.