Effects of supplemental progesterone after artificial insemination on expression of interferon-stimulated genes and fertility in dairy cows

Abstract

The objectives of the current study were to evaluate the effects of supplemental progesterone after artificial insemination (AI) on expression of IFN-stimulated genes (ISG) in blood leukocytes and fertility in lactating dairy cows. Weekly cohorts of Holstein cows were blocked by parity (575 primiparous and 923 multiparous) and method of insemination (timed AI or AI on estrus) and allocated randomly within each block to untreated controls, a controlled internal drug release (CIDR) containing 1.38g of progesterone from d 4 to 18 after AI (CIDR4), or a CIDR on d 4 and another on d 7 after AI and both removed on d 18 (CIDR4+7). Blood was sampled to quantify progesterone concentrations in plasma and mRNA expression in leukocytes for the ubiquitin-like IFN-stimulated gene 15-kDa protein (ISG15) and receptor transporter protein-4 (RTP4) genes. Pregnancy was diagnosed on d 34±3 and 62±3 after AI. Treatment increased progesterone concentrations between d 5 and 18 after AI in a dose-dependent manner (control=3.42, CIDR4=4.97, and CIDR4+7=5.46ng/mL). Cows supplemented with progesterone tended to have increased luteolysis by d 19 after AI (control=17.2; CIDR4=29.1; CIDR4+7=30.2%), which resulted in a shorter AI interval for those reinseminated after study d 18. Pregnancy upregulated expression of ISG in leukocytes on d 19 of gestation, but supplementing progesterone did not increase mRNA abundance for ISG15 and RTP4 on d 16 after insemination and tended to reduce mRNA expression on d 19 after AI. For RTP4 on d 19, the negative effect of supplemental progesterone was observed only in the nonpregnant cows. No overall effect of treatment was observed on pregnancy per AI on d 62 after insemination and averaged 28.6, 32.7, and 29.5% for control, CIDR4, and CIDR4+7, respectively. Interestingly, an interaction between level of supplemental progesterone and method of AI was observed for pregnancy per AI. For cows receiving exogenous progesterone, the lower supplementation with CIDR4 increased pregnancy per AI on d 62 in cows inseminated following timed AI (CIDR4=39.2; CIDR4+7=27.5%); in those inseminated following detection of estrus, however, the use of a second insert on d 7 resulted in greater pregnancy per AI (CIDR4=26.9; CIDR4+7=31.5%). Pregnancy loss did not differ among treatments. Supplemental progesterone post-AI using a single intravaginal insert on d 4 was beneficial to pregnancy in cows inseminated following timed AI, but incremental progesterone with a second insert on d 7 did not improve fertility of dairy cows.

Interferon-tau and fertility in ruminants

“…Results from various studies have reported an increase (Monteiro et al 2014), no change (Stevenson et al 2007, Monteiro et al 2015 or a decrease (Parr et al 2014) in pregnancy per AI (P/AI) for cows supplemented with exogenous P4 after ovulation compared with untreated controls. Although several studies evaluated the effect of decreasing P4 concentrations after ovulation on the uterine environment and embryo development (Forde et al 2011, few studies have evaluated the effect of decreasing P4 after ovulation on establishment of pregnancy (Kenyon et al 2013, Carvalho et al 2017).…”

Effects of gonadotropin-releasing hormone administration or a controlled internal drug-releasing insert after timed artificial insemination on pregnancy rates of dairy cows

“…In addition, another study showed that use of a CIDR insert from 3.5 to 10 days post-insemination increased the circulating progesterone concentration and tended to increase the pregnancy rate [10]. However, a number of studies using CIDR insert treatment post-insemination, in which the timing and duration of CIDR insert use varied, reported no beneficial effects on pregnancy outcomes [182734]. It is unclear why only a few studies have reported beneficial effects on pregnancy outcomes.…”

“…Several studies demonstrated that a CIDR insert increased the circulating progesterone concentration [2410]. However, many studies reported no improvement in pregnancy rates [2121834]. Moreover, only a few studies using a CIDR insert post-insemination comprising small numbers of experimental cows reported beneficial effects on pregnancy outcomes [916], indicating the need for more extended field trials.…”

A utilização de progesterona injetável, pós inseminação artificial em tempo fixo, em vacas de leite de alta produção como estratégia para melhoria da eficiência reprodutiva em propriedade leiteira

“…Conforme descrito anteriormente, foram submetidos ao experimento prático, O resultado para TC60 corrobora com o estudo de Souza (2015), que não obteve diferença na taxa de concepção aos 60 dias. Os resultados de não significância em relação a taxa de concepção tanto aos 30 dias como aos 60 dias também corroboram com outros trabalhos que utilizaram a suplementação de progesterona por implantes intravaginais em diferentes períodos pós IATF (MANN et al, 2001;O´HARA et al, 2013;SOUZA et al, 2013;MONTEIRO Jr et al, 2014;PARR et al, 2014;MONTEIRO-JR et al, 2015;NISHIMURA et al, 2018). Fonte: Dados da pesquisa.…”

“…Denotaram significante aumento de progesterona sanguínea, porém não obtiveram diferença na taxa de concepção das vacas.Demonstraram, com isso, que a suplementação na 2ª metade da fase luteal não trouxe melhoria na mortalidade embrionária precoce. Vários outros autores(SOUZA et al, 2013;MONTEIRO Jr et al, 2014;O´HARA et al, 2013) observaram efeito negativo da suplementação exógena de progesterona em diferentes situações, tanto com uso de dispositivos quanto com uso de formas injetáveis.Parr et al (2014) observaram diminuição de 12 pontos percentuais na relação de prenhez por inseminação, quando foram utilizados um dispositivo de liberação lenta de progesterona, entre os dias 4 e 9 pós inseminação, em vacas de leite, com um lote tratado em comparação com o grupo controle. Também não foi encontrada diferença na taxa de prenhez dos estudos de Monteiro Jr et al (2015), em que suplementaram vacas com dispositivo intravaginal de progesterona do dia 3 ao dia 20 pós IATF.…”