ENDOCRINE AND METABOLIC DISORDERS

Hormonal and metabolic disorders are major factors that can disrupt the function of the HPO axis and play a significant role in delayed ovulation in cows [3]. These disorders include hypothyroidism, hyperprolactinemia, insulin resistance, and general metabolic stress, all of which can alter gonadotropin production, follicle development, and ovarian responsiveness to the LH surge [85].

Hypothyroidism decreases basal metabolic rate, alters reproductive hormone regulation, and reduces ovarian sensitivity to gonadotropins [86]. Clinically, it is characterized by low circulating Triiodothyronine and Thyroxine, often accompanied by lethargy, reduced milk yield, and poor reproductive performance. Low thyroid hormone levels decrease IGF-1 production, impair follicle growth, and reduce steroidogenesis, preventing estradiol from reaching the threshold needed to trigger a robust LH surge [87, 88]. Hypothyroidism may also increase thyrotropin-releasing hormone, stimulating prolactin release and further disrupting the estrous cycle [89].

Hyperprolactinemia directly suppresses GnRH secretion [90]. Elevated prolactin reduces LH pulse frequency, impairs granulosa cell responsiveness to FSH, and inhibits oocyte maturation [91]. It also decreases estradiol synthesis by interfering with steroidogenic enzymes [92]. It is important to distinguish physiological postpartum hyperprolactinemia, transient elevations in early lactation supporting milk production, from pathological hyperprolactinemia, where persistently high prolactin outside the normal postpartum period disrupts GnRH/LH secretion and ovulation. Failure to reach estradiol thresholds prevents the LH surge, making pathological hyperprolactinemia a recognized contributor to delayed ovulation and anestrus [93].

Insulin resistance and metabolic stress impair ovarian function by reducing insulin signaling efficacy, which disrupts follicle development and estradiol synthesis through IGF-1 interactions [59, 94, 95]. Clinically, insulin resistance is often associated with overconditioned cows, elevated circulating insulin or glucose, reduced insulin sensitivity in early lactation, and poor reproductive responses despite adequate nutrition [60]. This condition limits energy availability to the ovaries and decreases follicular response to LH, contributing to delayed ovulation [96].

Metabolic stress, including NEB in early lactation, reduces blood IGF-1, glucose, and insulin [97]. This suppresses GnRH secretion, lowers LH pulse amplitude, and slows dominant follicle growth [98]. Elevated lipid metabolites such as NEFA and BHB can be toxic to granulosa cells and oocytes, impairing follicle quality and promoting persistent follicles [99]. Collectively, these endocrine and metabolic disruptions delay ovulation and impair functional CL formation [100].