Research articleEffects of age and altrenogest treatment on conceptus development and secretion of LH, progesterone and eCG in early-pregnant mares
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.
References (38)
- et al.
Use of altrenogest to prepare ovariectomized mares as embryo transfer recipients
Theriogenology
(1986) - et al.
Ovariectomized steroid-treated mares as embryo transfer recipients and as a model to study the role of progestins in pregnancy maintenance
Theriogenology
(1988) - et al.
Luteal blood flow and progesterone production in mares
Anim Reprod Sci
(2007) - et al.
Embryonic loss in mares: incidence and ultrasonic morphology
Theriogenology
(1985) - et al.
Effects of time of progesterone supplementation on embryo development and interferon-tau production in the cow
Vet J
(2006) - et al.
Role of progesterone in mobility, fixation, orientation, and survival of the equine embryonic vesicle
Theriogenology
(1987) - et al.
The effect of Regu-Mate, a synthetic progestin, on early pregnancy maintenance, conceptus growth, and corpora lutea development in pregnant pony mares
Equine Vet Sci
(1991) - et al.
A review of implantation and early placentation in the mare
Placenta
(2009) - et al.
The effect of exogenous progestins on endogenous progesterone secretion in pregnant mares
Theriogenology
(1986) - et al.
The effect of skin allografting on the equine endometrial cup reaction
Theriogenology
(2007)
Effect of uterine inflammation and ultrasonically detected uterine pathology on fertility in the mare
J Reprod Fertil
Reproductive efficiency of intensively managed Thoroughbred mares in Newmarket
Equine Vet J
Luteal deficiency and embryo mortality in the mare
Reprod Dom Anim
Progestagen therapy of ovariectomized pregnant mares
J Reprod Fert
Failure of hydroxyprogesterone caproate to maintain pregnancy in ovariectomised mares
Equine Vet J
The inability of some synthetic progestagens to maintain pregnancy in the mare
Equine Vet J
Regulation of circulating gonadotropins by the negative effects of ovarian hormones in mares
Biol Reprod
Pituitary and chorionic gonadotrophic control of ovarian function during early pregnancy in equids
J Reprod Fertil
Collection technique and progesterone concentration of ovarian and uterine venous blood in mares
J Anim Sci
Cited by (45)
Seasonal absence of supplementary corpora lutea in pregnant mares and the relationship with pregnancy loss
2023, Journal of Equine Veterinary ScienceLow progesterone concentration in early pregnancy is detrimental to conceptus development and pregnancy outcome in horses
2023, Animal Reproduction ScienceAbiotic transformation of synthetic progestins in representative soil mineral suspensions
2023, Journal of Environmental Sciences (China)Biotransformation kinetics and pathways of typical synthetic progestins in soil microcosms
2023, Journal of Hazardous MaterialsCitation Excerpt :Synthetic progestins are widely used for cancer treatment, as oral contraception, and in hormone replacement therapy; additionally, they are used as feed additives to treat livestock diseases and promote animal growth [4,5]. Typical synthetic progestins include gestodene (GES), the most potent third-generation oral contraceptive [6]; altrenogest (ALT), a swine and equine veterinary drug used to maintain pregnancy [7]; and medroxyprogesterone acetate (MPA), a medicine used to treat abnormal uterine bleeding, secondary amenorrhea, dysmenorrhea, and endometriosis [8]. Worldwide consumption data for GES, ALT, and MPA are generally lacking; however, several attempts have been made to estimate their consumption in European countries [9,10].
Low plasma progesterone concentration during the early luteal phase delays endometrial development and the beginning of placentation in mares
2022, Animal Reproduction ScienceCitation Excerpt :This finding explains changes in endometrial function as reflected by uterine fluid amino acid composition (Beyer et al., 2019). Similarly, progestin supplementation enhanced conceptus growth in older mares until 45 days of pregnancy, a period considered critical for equine pregnancy due to implantation and the beginning of placental development (Willmann et al., 2011b). An experimentally reduced progesterone concentration early in the luteal phase delayed development of the equine conceptus at least until placentation.