Elsevier

Theriogenology

Volume 75, Issue 3, February 2011, Pages 421-428
Theriogenology

Research article
Effects of age and altrenogest treatment on conceptus development and secretion of LH, progesterone and eCG in early-pregnant mares

https://doi.org/10.1016/j.theriogenology.2010.05.009Get rights and content

Abstract

The treatment of early pregnant mares with a history of repeated early embryonic loss with the progestin altrenogest has become routine; however no controlled studies on the efficiency of altrenogest to prevent embryonic losses are available so far. In the present study, we have investigated effects of altrenogest treatment in mares on conceptus development and the secretion of LH, progesterone, and eCG until day 100 of pregnancy. In addition, differences related to age of mares were assessed. Mares were treated with altrenogest (0.044 mg/kg per os once daily) or sunflower oil (10 ml per os once daily) from day 6 to day 100 after ovulation. Blood samples for analysis of LH, progesterone, and eCG were collected. The size of the embryonic vesicle and embryo/fetus was determined by ultrasound. No difference in the per cycle pregnancy rate between altrenogest-treated (75%) and sunflower oil-treated mares (74%) was detected (n.s.). A significant effect of age but not of altrenogest treatment on mean diameter of the embryonic vesicle was found between days 12 and 22 of pregnancy (e.g. day 15: control, 4–8 years: 22.9 ± 1.0 mm, >8 years: 22.0 ± 1.7 mm, altrenogest, 4–8 years: 26.1 ± 2.0 mm, >8 years: 20.4 ± 1.0 mm, P < 0.05). A significant effect of age and treatment on size of the embryo proper between days 30 and 45 was detected (P < 0.05). In the control group but not in the altrenogest group, size of the embryo proper respective fetus was negatively correlated with age of the mares (day 30: r = −0.834, P < 0.05; day 35: r = −0.506, P < 0.05). Plasma concentrations of LH and progesterone were neither effected by age nor by treatment of mares, but significant effects of age and altrenogest treatment on eCG concentrations between days 40 and 130 were detected (P < 0.05). The present study demonstrates for the first time a positive influence of altrenogest-treatment on a retarded development of the embryo respective fetus around the beginning of placentation in mares older than 8 years.

Introduction

Early pregnancy loss until approximately day 20 after ovulation is a major reason for low reproductive efficiency in subfertile mares [1], [2]. Treatment of early pregnant mares with a history of repeated early embryonic loss with the progestin altrenogest has become routine [3]. Altrenogest has been shown to efficiently maintain pregnancy in ovariectomized embryo recipient mares until the onset of placental progestin synthesis [4], [5]. Similarly, altrenogest prevents embryonic loss in early pregnant mares after ovariectomy or induction of luteolysis [6], [7], [8]. However, no controlled studies on the efficiency of altrenogest administration for prevention of embryonic loss in fertile and subfertile mares are available so far.

After ovulation, pregnancy is maintained by progesterone from the corpus luteum. During the initial phase of gestation in mares, maximal concentrations of progesterone are reached on day 8 after ovulation and subsequently slowly decrease [9]. This is paralleled by a progressive decrease in the mean cross-sectional area of the CL from day 4 of the cycle [10]. Maternal recognition of pregnancy in the mare occurs between days 10 and 14 after ovulation [9]. However, its exact mechanism is still unknown in the horse. After recognition of pregnancy, the primary corpus luteum is responsible for maintenance of pregnancy for the next 3 to 4 weeks. During this period, progesterone secretion may decrease to concentrations much lower than during the first 10 days of pregnancy [3]. Development of accessory corpora lutea as a result of endometrial cup formation and associated eCG synthesis starting approximately on day 37 [11] leads to a second pronounced increase in progesterone concentration from day 40 onwards [12]. A gradual degeneration of the endometrial cups and consequently a loss of eCG synthesis capacity is initiated after day 70 of pregnancy by an immune reaction of the endometrium, subsequently also resulting in regression of the accessory corpora lutea [13]. The primary corpus luteum itself is maintained until day 160 to 180 after ovulation [14], [12]. However, placental progestin synthesis in the pregnant mare starts as early as day 60 after ovulation. Therefore, from day 70 onwards, circulating progestin concentration in the pregnant mare is considered a mixture of luteal progesterone and placental progestins. From day 160 of pregnancy onwards, progesterone itself can no longer be detected in the maternal circulation [15].

In approximately 10% of fertile mares, early embryonic loss occurs. In subfertile mares, this condition is seen even more frequently and also occurs over a longer period of time [1]. Insufficient growth and development of the conceptus are considered major reasons for early embryonic losses. Thus in embryos with subnormal size, the loss rate is higher than in embryos with normal size [1], [16], [17], [18]. In aged mares, the quality of early embryos is inferior than in young mares [19]. Approximately 60% of early pregnancy losses occur between days 15 and 35 [2]. However, it is unclear whether subnormal progesterone concentration contributes to failure of embryonic development in the horse [3]. In cows, a positive relationship between progesterone concentration in maternal plasma and development of the embryo, resulting in a stronger antiluteolytic signal has been demonstrated [20], [21], [22]. In the mare, the presence of progesterone seems to be a prerequisite for mobility of the conceptus as well as its subsequent fixation and orientation in the uterus [23].

In the present study, we have investigated effects of altrenogest treatment of early-pregnant mares on conceptus development and secretion of the reproductive hormones LH, progesterone, and eCG. Differences between altrenogest-treated and non-treated mares in relation to age of the mares were assessed.

Section snippets

Animals

Mares were warmblood mares (n = 32) of the Brandenburg breed belonging to the broodmare herd of the Brandenburg State Stud at Neustadt (Dosse), Germany. Age, weight, and reproductive history of mares are shown in Table 1. Mares were kept in groups of 8 to 10 animals. Until the end of April, mares were housed in spacious group stables. During this time they were fed oats (3 kg per mare and day) and minerals thrice daily. Hay was given ad libitum. During daytime, the mare groups spent several

Fertility of mares and development of the conceptus

No difference in the pregnancy rate per cycle between altrenogest-treated (75%) and placebo-treated mares (74%) was detected (n.s.). None of the mares pregnant on day 12 after ovulation subsequently lost her pregnancy and all mares gave birth to healthy mature foals during the next spring.

The size of the embryonic vesicle increased significantly from day 12 to day 22 after ovulation irrespective of age and treatment (P < 0.05, Fig. 1). A significant effect of age on mean diameter of the

Discussion

In the present study, effects of age and altrenogest treatment on conceptus development and the secretion of reproductive hormones during early pregnancy in mares were investigated. One important finding is that conceptus development is limited in mares aged >8 years in comparison to mares between 4 and 8 years of age. In the older animals, size of the embryonic vesicle as well as size of the embryo proper respective fetus was smaller than in the younger mares. Embryonic vesicles that

Acknowledgements

The study was supported by a fellowship from the Mehl-Muelhens Foundation to Conrad Willmann. The authors are grateful to Dr. P. Ascher, Intervet-Schering-Plough Animal Health for the donation of Regumate equine.

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