PROCESS DESCRIPTION: CHANGES IN HORMONAL PATTERNS DURING EQUINE GESTATION

AMANDA FLANAGAN ENGL 202C SECTION 014 MARCH 16, 2012

AUDIENCE AND SCOPE OF DESCRIPTION

The purpose of this technical description is to provide the reader with a basic understanding of how hormone secretion patterns change throughout equine gestation (pregnancy in horses). This description will provide a general overview of the entire process of equine pregnancy, focusing specifically on the major hormones involved in the process. After reading this document, the audience will be able to identify the major hormones involved in equine pregnancy, how they function, and how these hormones interact with one another in order to maintain pregnancy. The intended audience for this document is college students who are interested in animal sciences or life sciences in general, with some prior knowledge of basic sciences. This document is ideally suited for inclusion in a textbook or as a separate supplemental document. The information provided in this description should build upon previous knowledge of animal and life sciences, as well as provide new information and an in depth analysis of a specific scientific process. Overall, this information will be most beneficial to students interested in furthering their scientific studies, preparing for veterinary school, or pursuing a career in the equine industry.

KEYWORDS
EQUINE GESTATION MARE HORMONE LUTEINIZING HORMONE (LH) FOLLICLE STIMULATING HORMONE (FSH) CORPUS LUTEUM (CL) PROSTAGLANDIN (PG) PROGESTERONE ENDOMETRIAL CUPS EQUINE CHORIONIC GONADOTROPIN (eCG) OESTROGEN GONAD PARTURITION

INTRODUCTION
Equine gestation refers to the period of time during which the mare (female horse) is pregnant. It begins with conception (fertilization of an egg by a sperm) and ends with parturition (birth). On average, equine gestation lasts 340 days, although this period of time can range from 320-380 days. This period of time involves extensive changes in the types and patterns of hormones synthesized and secreted by both the mare and developing fetus. Hormones are chemicals released by cells or glands in one part of the body that send out messages that cause cells in other parts of the body to produce a specific response. The

major hormones involved in equine reproduction and gestation are luteinizing hormone (LH), follicle stimulating hormone (FSH), prostaglandins (PG), progesterone, equine chorionic gonadotropin (eCG), and oestrogens. Figure 1 summarizes the levels of these hormones (Y axes), their sources (shapes above the graph) and timeframes of secretion (X axis) below. It may also be helpful to keep this figure in mind throughout the remainder of this process description, as it provides a very complete visualization of the overall process to be discussed.

FIGURE 1. EVENTS OF PREGNANCY, DEVELOPMENT AND HORMONAL CHANGES IN THE MARE

The remainder of this document will explore each of these hormones individually in order to better understand how they function and why, as well as how they interact with other hormones to maintain pregnancy. By the end of this description it will be clear not only how each individual hormone functions, but also how the entire process of equine gestation is supported by the relationships between these hormones.

LUTEINIZING HORMONE AND FOLLICLE STIMULATING HORMONE

Although less important throughout pregnancy and parturition, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are essential in the overall process of equine reproduction. Without them, gestation could not occur. The synthesis and secretion of these hormones are controlled by an internal network called the hypothalamic-pituitary-gonadal axis (HPG axis). As can be inferred by its name, the HPG axis involves hormonal communication and regulation between the hypothalamus (in the brain), the pituitary gland

(in the brain) and the gonads (ovaries). The relationship between these three systems is summarized in Figure 2. First, gonadotropin-releasing hormone (GnRH) is released from the hypothalamus to stimulate LH and FSH production in the pituitary gland. LH and FSH are then released from the pituitary to act on the ovaries, allowing for the possibility of reproduction.

FIGURE 2. HYPOTHALAMIC-PITUITARY-GONADAL AXIS IN THE FEMALE

LH and FSH both have similar synthesis and secretion patterns, however they have vastly different functions. When FSH reaches the ovary it is responsible for stimulating oocyte (egg) development. This oocyte will eventually be released from the ovary into the oviduct via ovulation, where it will be fertilized to begin gestation. FSH continues to occilate throughout the first one-third of gestation (Figure 1), however this mechanism is not entirely understood. LH also acts on the ovary, however it is responsible for inducing ovulation of the developing oocyte. LH also plays a role in formation of the primary corpus luteum (CL), a temporary structure important in the production of progesterone (the major hormone responsible for maintaining pregnancy).

PROSTAGLANDINS
There are two types of prostaglandins important in equine gestation: PGF2 and PGE2. Like LH and FSH, circulating levels of prostaglandins are less prevalent and important throughout the majority of gestation, however, they are still imperative in the overall reproductive cycle. This is because in the absence of successful pregnancy, the mares uterus releases PGF2 to lyse (break down) the developing CL. Without a CL, pregnancy cannot persist and the reproductive cycle starts over. Because of this, PGF2 is also a key hormone in determining initial pregnancy status. The suppression of PGF2 secretion in pregnant mares is indirectly controlled by the fetus via PGE2 secretion. Maternal recognition of pregnancy (MRP) is imperative in signaling

the presence of an embryo, such that the mares body can begin to make the necessary adjustments in order to sustain pregnancy. Unlike in many other species, however, in horses there is no specifically known hormone that signals this change. Thus, it is accepted that the physical movement of the embryo throughout the uterus acts as this MRP factor. This migration down the oviduct, then into and throughout the uterus is assisted by the secretion of PGE2 from the embryo (Figure 3). PGE2 not only assists embryo travel, but also prevents PGF2 secretion by the mare, which, as previously stated, would break down the CL and terminate the pregnancy. This secretion continues until around Day 16 of gestation, when the embryo becomes implanted in the uterus.

FIGURE 3. DAY 5 OF GESTATION: EQUINE EMBYRO SECRETING PGE2 TO ASSIST ITS TRAVEL INTO THE UTERUS FOR IMPLANTATION.

Once the embryo is implanted, the major hormonal and developmental changes of gestation begin, and prostaglandins cease to be a factor in the process. It is at this point that gestation becomes much more apparent and easier to monitor, such that the hormones and structures initially referenced in Figure 1 become the major players, specifically, progesterone.

PROGESTERONE
Progesterone is known as the pregnancy hormone. Of all of the hormones involved in reproduction and gestation, none is more important in maintaining pregnancy than progesterone. Progesterone is responsible for maintaining pregnancy primarily by preventing the mare from cycling back into estrus (period of sexual receptivity and nonpregnancy) and maintaining the endometrium (lining of the uterus). Progesterone is synthesized by and secreted from the primary CL. The primary CL, as demonstrated in Figure 4, forms from the ruptured ovulation fossa (site of ovulation on the ovary) following ovulation. This CL will remain in tact and continue to secrete progesterone throughout the first one-third of pregnancy.

FIGURE 4. DEVELOPMENT OF THE PRIMARY CL FROM THE RUPTURED OVARY

There is also a spike in progesterone at the time of parturition. The cause of this spike is scientifically unknown, although it may be related to some of progesterones secondary effects, including closing the cervix and quelling uterine contractions. Additionally, circulating progesterone levels throughout the first trimester of pregnancy are increased by the formation of secondary CLs. These secondary CLs are formed by equine chorionic gonadotropin (eCG).

EQUINE CHORIONIC GONADOTROPIN

Equine chorionic gonadotropin (eCG) is secreted by structures called endometrial cups. Endometrial cups first appear between Days 36 and 40 of gestation and develop from a structure on the placenta known as the chorionic girdle following embryonic implantation. Once implanted, these endometrial cups migrate through the endometrium, wherein eCG is secreted. The development of endometrial cups from the chorionic girdle can be visualized in Figure 5 below (EC = endometrial cup).

FIGURE 5. ENDOMETRIAL CUPS DEVELOP FROM THE MARES CHORIONIC GIRDLE TO PRODUCE eCG, WHICH PRODUCES SECONDARY CLS TO CONTINUE PROGESTERONE PRODUCTION.

Maximum secretion of eCG occurs between Days 55 and 70 of gestation, when the endometrial cups are the largest. In horses, eCG has LH-like activity, causing the formation of secondary CLs, which produce additional progesterone. It is also speculated that eCG regulates immunological activity in the mare in order to maintain pregnancy. Around Day 120 of gestation the endometrial cups degenerate, causing a decline in eCG levels and a loss of secondary CLs. Without the secondary CLs, progesterone levels also drop. From this point, pregnancy is maintained by hormones secreted by the fetus, leading to the production of oestrogems.

OESTROGENS
As shown in Figures 6-7, development of fetal gonads (sex organs) begins at Day 80 of gestation and continues up to Day 260. Hormones and substances produced by the gonads are important in maintaining pregnancy from their development until parturition around Day 340.

FIGURES 6-7. DEVELOPMENT OF FETAL GONADS AND OESTROGEN PRODUCTION; FETUS AT DAY 80 (LEFT) AND DAY 240 (RIGHT) OF GESTATION.

The fetal gonads are important in maintaining pregnancy because they produce substances that can be metabolized by the placenta. The placenta is the structure and source of nutrient exchange between the mare and fetus. As such, the substances produced by the fetal gonads are converted by the placenta into oestrogen hormones. The primary role of oestrogens in maintaining pregnancy is to stimulate fetal growth by increasing blood flow to the endometrium. Increased blood flow then increases the food supply to the developing fetus and supports the rapid increase in fetal size that occurs in late gestation. Oestrogen levels drop off prior to parturition as progesterone levels rise again, most likely to manage the intensity of uterine contractions.

CONCLUSION

Understanding the changes in hormonal composition and levels throughout equine gestation is best done by considering the individual hormones involved: 1. FSH first develops the oocyte, then LH causes ovulation of the oocyte and assists in formation of the primary CL. 2. If the mare does not become pregnant, prostaglandin F2 is secreted by the uterus to break down the primary CL. If the mare does become pregnant, the embryo secretes prostaglandin E2 to assist its migration to and implantation in the uterus, as well as to prevent the production of PGF2 by the mare. 3. Once implantation occurs, the primary CL is maintain and produces progesterone, which maintains pregnancy by preventing the mare from cycling back into estrus and maintaining the endometrium. 4. eCG is produced by endometrial cups and is responsible for the formation of secondary CLs. These secondary CLs continue to produce progesterone until Day 120, when the endometrial cups degenerate, causing a decline in eCG. 5. After degeneration of the endometrial cups, pregnancy is maintained by substances produced by the fetal gonads that are metabolized by the placenta, producing oestrogens. Oestrogens maintain pregnancy by increasing blood flow and nutritional support to the endometrium and stimulating final fetal growth up to parturition. Understanding these hormonal changes and patterns are essential in understanding equine gestation and reproduction in its entirety. When considering this process, it is important not only to understand the types and functions of the individual hormones involved, but also how they all work together to maintain the scope of the entire process and final, big picture, product, as demonstrated in Figure 8.

FIGURE 8. THE FINAL PRODUCT: MARE AND FOAL

WORKS CITED

FIGURE 1 (UNMODIFIED): Allen, W.R. Maternal recognition and maintenance of pregnancy in the mare. Graph. Animal Reproduction. Oct./Dec. 2005. 14 March 2012. <http://www.cbra.org.br/pages/publicacoes/animalreproduction/ issues/download/v2n4/Maternal%20recognition.pdf>. FIGURE 2 (UNMODIFIED): Homburg, R. The Mechanism of Ovulation. Flowchart. Glob. libr. womens med. Oct. 2008. 14 March 2012. <http://www.glowm.com/index.html?p=glowm. cml/section_view&articleid=289>. FIGURE 3 (CROPPED): Allen, W.R. Maternal recognition and maintenance of pregnancy in the mare. Graph. Animal Reproduction. Oct./Dec/ 2005. 14 March 2012. <http://www.cbra.org.br/pages/publicacoes/animalreproduction/ issues/download/v2n4/Maternal%20recognition.pdf>. FIGURE 4 (CROPPED): Peterson, Robin. Normal Mare Anatomy. Sketches. TheHorse.com. 14 March 4, 2012. < http://www.thehorse.com/images/content/0703/repro.html>. FIGURE 5 (CROPPED): Bowen, R. Endometrial Cups and Secretion of Equine Chorionic Gonadotropin. Photographs. Colorado State University. March 2000. 14 March 2012. < http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/ endocups.html>. FIGURES 6-7 (UNMODIFIED): Fetus Development. Sketches. Shenandoah Miniature Training and Foaling Center. Oct. 2009. 14 March 2012. < http://www.shenandoahmini.com/ fetaldevelopment.html>. FIGURE 8 (RESIZED): Newborn Love How Precious! Photograph. Barnmice Equestrian Social Community. May 2009. 14 March 2012. <http://www.barnmice.com/ forum/topics/newborn-love-how-precious>.