IV. ENDOCRINOLOGY OF PREGNANCY

  1. OVERVIEW

    The endocrinology of equine pregnancy is unique. Endometrial cups, ECG, accessory corpora lutea, the active gonad of the equine fetus, the 5 a pregnanes and elevated estrogens (in serum and urine) distinguish equine pregnancy.

  2. OVARIAN DYNAMICS DURING PREGNANCY

    Ovarian activity is intense during early equine pregnancy.

    1. Follicular growth and luteinization- Following maternal recognition of pregnancy, follicular activity continues on the ovaries in a fashion similar to vernal transition; large follicles grow and regress up to about day 140. However, after about day 40, some of these follicles ovulate, forming secondary corpora lutea, or luteinize without ovulating, forming accessory corpora lutea. Great individual variation occurs between mares: some never form additional corpora lutea, others form several additional corpora lutea. Regardless of when they emerge, the corpora lutea actively secrete progesterone, and persist until about day 180.

    2. Luteal responses- Luteal responses during early pregnancy can be divided as follows.

      1. First luteal response. Primary CL maintained past day 14.

      2. Second luteal response. Resurgence (second wind) of primary CL at about day 30 .

      3. Third luteal response. Formation of secondary CL's (day 40-70) and accessory CL's (day 40-150).

  3. EQUINE CHORIONIC GONADOTROPIN

    It may seem boring right now, but pregnant mare serum gonadotropin (PMSG) caused quite a stir after its discovery in the 1930's due to its ability to stimulate follicular growth in many different animals (but not horses!). Equine chorionic gonadotropin (ECG) is the correct term for this hormone today; its existence is a unique feature of equine pregnancy.

    1. Endometrial cups- At about day 35, portions of the trophoblast known as the chorionic girdle (at the junction of the yolk sac and allantois) burrow into the endometrium, and become separated from the placenta. These invasive (foreign) cells multiply, induce an inflammatory reaction, and develop into the endometrial cups, secreting ECG. Plasma levels of ECG rapidly rise from about day 35, peaking between 60-80 days, and decline to baseline by about 100-120 days, when the endometrial cups are sloughed (forming chorioallantoic pouches). Great individual variation exists in the ECG profile of different mares.

    2. Function of ECG- ECG apparently provides the luteinization signal to drive the second and third luteal responses. It does not, as once was thought, stimulate follicular development in pregnancy, which is probably the result of FSH pulses from the pituitary. Follicular development precedes formation of the endometrial cups.

  4. FETAL GONADS

    The fetal gonad is active throughout much of gestation, increasing in size to greater than the maternal gonad at about day 210-240, before shrinking to its smaller size at birth. It becomes a steroid factory, exchanging steroids with the placenta, which often modifies them. The details of all the exchanges between equine fetal gonad and placenta have yet to be elucidated. It is convenient to consider the fetal gonad and placenta as a single steroidogenic entity known as the fetoplacental unit, which first becomes active at about day 70 of gestation.

  5. PROGESTOGENS DURING PREGNANCY

    Progestogens are a family of compounds having progesterone-like activity. A source of progestogens is necessary to support pregnancy throughout gestation in the mare.

    1. Luteal progesterone- For the first half of gestation, progesterone from luteal tissue supports pregnancy. Luteal progesterone levels peak at about day 100, and subside to baseline by about day 180-200.

    2. Progestogens from the fetoplacental unit- Progestogens known as 5a pregnanes first appear in maternal circulation at 50-70 days of gestation, released into the circulation by the fetoplacental unit. Ovariectomy of a mare before day 70 can result in abortion, but following ovariectomy at day 140 the fetus will be carried to term successfully. The fetoplacental unit thus assumes maintenance of pregnancy between 70 and 140 days. Interestingly, levels of 5a pregnanes increase dramatically towards the end of gestation, peaking about 5 days prior to parturition. The mare, unlike other domestic animals, delivers her young in the face of high progestogens.

  6. ESTROGENS DURING PREGNANCY

    High levels of estrogens are a distinctive feature of equine pregnancy.

    1. Ovarian sources- Estrogen remains relatively low in pregnant mare until day 35, when it suddenly increases, produced by ovarian luteal tissue, reaching levels exceeding estrus. Presumably its rise is associated with secretion of ECG. Ovarian sources of estrogens gradually subside by about day 120.

    2. Fetoplacental sources- A second surge in estrogens occurs at about day 60 of gestation, when circulating estrogens synthesized by the fetoplacental unit appear in the circulation. A massive rise continuing from day 70 to day 100 is likely to only occur in mares with normal fetal development. Estrogen production appears to follow gonadal size closely, peaking at about day 210-240, and gradually decreasing, though still detectable, as gestation continues to term. The elevated levels of conjugated estrogens can be used as a pregnancy test in the horse by immunoassay of blood, urine, or milk from day 45 to term. Estrogens can be detected in the urine by the Cuboni test from day 150 to term. Measurement of estrone sulfate in feces has been used to determine pregnancy rates and fetal viability in feral horses.

  7. RELAXIN

    Relaxin is synthesized by the fetoplacental unit, first detectable about day 70, and peaking about day 200. It remains elevated through most of gestation. It is not released by the corpus luteum in the horse, unlike other species.