Mechanisms underlying reduced fertility in anovular dairy cows.

Resumption of ovulation after parturition is a coordinated process that involves recoupling of the GH/insulin-like growth factor 1 axis in the liver, increase in follicular development and steroidogenesis, and removal of negative feedback from estradiol in the hypothalamus. Infectious diseases and metabolic disorders associated with extensive negative energy balance during early lactation disrupt this pathway and delay first ovulation postpartum. Extended periods of anovulation postpartum exert long-lasting effects on fertility in dairy cows including the lack of spontaneous estrus, reduced pregnancy per artificial insemination (P/AI), and increased risk of pregnancy loss. Concentrations of progesterone in anovular cows subjected to synchronized programs for AI are insufficient to optimize follicular maturation, oocyte competence, and subsequent fertility to AI. Ovulation of first wave follicles, which develop under low concentrations of progesterone, reduces embryo quality in the first week after fertilization and P/AI in dairy cows. Although the specific mechanisms by which anovulation and low concentrations of progesterone impair oocyte quality have not been defined, studies with persistent follicles support the involvement of premature resumption of meiosis and degradation of maternal RNA. Suboptimal concentrations of progesterone before ovulation also increase the synthesis of PGF2α in response to oxytocin during the subsequent estrous cycle, which explains the greater incidence of short luteal phases after the first AI postpartum in anovular cows compared with estrous cyclic herd mates. It is suggested that increased spontaneous luteolysis early in the estrous cycle is one of the mechanisms that contributes to early embryonic losses in anovular cows. Anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages of pregnancy. Transcripts involved with control of energy metabolism and DNA repair were downregulated, whereas genes linked to apoptosis and autophagy were upregulated in Day 15 conceptuses collected from anovular cows compared with estrous cyclic counterparts. Similar changes in conceptus transcriptome were not observed in estrous cyclic cows induced to ovulate follicles that grew under low and high concentrations of progesterone, indicating an effect of anovulation on embryonic development that is not mediated solely by progesterone concentrations before ovulation. Finally, risk factors for anovulation have direct effects on embryo development and uterine receptivity to pregnancy that complement those determined by insufficient concentrations of progesterone during follicular growth. One approach to minimize the impact of anovulation on fertility is supplementation with progesterone during recruitment, selection and final stages of development of the preovulatory follicle. It is suggested that a minimum of 2.0 ng/mL of progesterone is needed during growth of the preovulatory follicle to achieve P/AI similar to that of cows growing the preovulatory follicle during diestrus.