Steroids in the establishment and maintenance of pregnancy and at parturition in the mare

Historically, studies on the endocrinology of pregnancy and parturition in horses have made major contributions of relevance to mammals in general. Recent use of liquid chromatography mass spectrometry, measuring multiple steroid hormones simultaneously in blood, foetal and placental tissues throughout normal gestation, and in mares with experimentally induced placentitis, has advanced our current understanding of many of the unusual strategies seen during gestation and at foaling. This includes the stimulation of luteal steroidogeneisis by equine chorionic gonadotropin (eCG) from the endometrial cups, resulting in additional androgen and oestrogen secretion. Progesterone declines as the endometrial cups and eCG disappears, replaced by 5α-dihydroprogesterone (DHP), a potent equine progesterone receptor (PR) agonist, as the chorioallantoic placenta develops. Placental steroidogenesis thereafter is influenced by foetal pregnenolone and dehydroepiandrosterone secretion, providing substrate for 5α-pregnane and oestrogen synthesis, an unusual example of a ‘foeto-placental unit’. Foetal gonadal dehydroepiandrosterone fuels placental oestrone sulphate secretion, peaking at higher concentrations in mares than any other species known, declining steadily thereafter to term. Additional 5α-reduced (DHP) metabolites increase from mid-gestation to peak concentrations 3–5 days before foaling, declining prepartum, most likely as a result of selective loss of placental SRD5A1 (5α-reductase) expression and activity. Similar changes occur in mares with experimentally induced placentitis, which is also associated with a decreased ratio of equine PR-B:PR-A in myometrium, suggesting that progestin withdrawal is both systemic (pregnanes) and local (receptor-dependent) in mares. In addition, some steroids detected during equine pregnancy by immuno-assay are not detected by mass spectrometry, further illustrating the immense value of this technology.

Foetal oestrogens and autism

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

Serum progesterone and oestrone sulphate concetrations for monitoring fertility in Sows

Blood samples were taken from 161 sows the days 19-21 (serum progesterone assessments), from 306 sows on days 24-30 (serum oestrone sulphate assessments) and from 150 sows on day 20 (serum progesterone assessments) and on days 26-29 (serum oestrone sulphate assessments) after service. Actual farrowing or abortion and signs of return to oestrus were used as criteria for pregnancy and non-pregnancy, respectively. Litter size was also recorded at each farrowing. The results showed that the overall accuracy of progesterone and oestrone sulphate for predicting pregnant sows was 90.7% and 97.2%, respectively. The highest accuracy of oestrone sulphate (100%) was noticed on days 27 and 28 after service. The overrall accuracy of the combination of both progesterone and oestrone sulphate assessments to detect pregnant sows was 97% and to detect non-pregnant sows was 100%. Significant correlation coefficients between serum oestrone sulphate concentration and litter size were found on days 24,26,27, 28,29 and 30, but the highest correlation coefficient was noticed on day 28 after service (r=0.51, Ρ, 0.001). Moreover, it was also found that mean litter size was significantly higher (P <0.05). in sows with serum oestrone sulphate concentrations > 1 ng/ml compared with concentrations < 1 ng/ml from day 26 up to day 30 after service. It is concluded that serum progesterone assessment helps in the determination of the non-pregnant sows early enough for problems related to failure of fertilization to be promptly dealt with. Serum oestrone sulphate concentration on day 28 after service can be used as an indicator of conception, as a predictor of small litter size and also can help in the estimation of embryonic mortality. The combination of these two assessments, in addition to their value in pregnancy diagnosis, can be useful in identifying concurrent reproductive problems in units with sub-optimal productivity.

Use of a deslorelin implant for influencing sex hormones and male behaviour in a stallion — Case report

This case report describes the use of a subcutaneously applied 4.7-mg deslorelin acetate implant in a three-year-old Arabian crossbred stallion showing unwanted strong male behaviour. Following deslorelin acetate implantation the stallion showed a short transitional increase in male behaviour. A ‘gelding-like’ behaviour was noted 15 days (D15) after treatment. The horse was surgically castrated at the owners request at D52 after treatment. Serum testosterone, oestradiol-17β and oestrone sulphate values decreased after deslorelin acetate implantation, but serum LH and FSH levels remained unchanged. Histopathological analysis of both testes and sperm analysis revealed a reduced spermatogenesis at D52. The testicular volume decreased after treatment. The use of a subcutaneously applied deslorelin acetate implant might be a promising tool to change the behaviour of aggressive stallions.