Indel mutations within the bovine HSD17B3 gene are significantly associated with ovary morphological traits and mature follicle number.

Given the intensive selection for increased milk production, it is imperative that the problem of declining fertility in dairy cows be reversed. In female mammals their reproductive traits and functioning is controlled by a finely tuned process balancing estrogens and androgens, in which androgens (e.g., testosterone) as a precursor substance can participate in estrogen synthesis by activating 17ß-hydroxysteroid dehydrogenase (17betaHSD). Being a key catalyst for testosterone synthesis, we hypothesized HSD17B3 gene is involved in the ovary's development and thereby capable of influencing cows' fecundity. Herein, to investigate the relationship between polymorphisms of the HSD17B3 gene and cow fertility, we characterized three insertion/deletion (indels) polymorphisms of this gene in 1110 healthy bovine ovaries. Their respective minimum allelic frequency (MAF) ranged from 0.180 to 0.482. For the ovary morphological traits, correlations revealed that both P1-D15-bp and P4-D19-bp demonstrated significant associations with ovarian height (P = 0.007 and 0.004, respectively), while P5-I5-bp was found to be significantly associated with the ovarian weight (P = 0.024). For ovarian volume, a significant correlation was uncovered between it and both polymorphisms of P4-D19-bp (P = 0.036) and P5-I5-bp (P = 0.045). Cows with either the DD genotype of P4-D19-bp or P5-I5-bp tended to have greater ovarian volume, a result consistent with their relationship to ovarian weight (P5-I5-bp) or height (P4-D19-bp). For the mature follicle traits, polymorphisms of P4-D19-bp were found significantly associated with the number of mature follicles (P = 0.045). Furthermore, expression levels of HSD17B3 differed significantly between the maximal and minimum groups of ovarian weight or volume, and the transcription factors GATA-1 and USF were predicted to bind P1-D15-bp and P4-D19-bp, respectively. This suggested the detected intron mutations could affect HSD17B3's transcription by regulating the binding of transcription factors, thereby affecting ovarian weight and other reproductive traits. As a potential effective molecular marker loci significantly related to traits of ovary and follicle, these three indels could be used in practical molecular marker-assisted selection (MAS) breeding programs, to optimize female fertility and enhance economic efficiency in the dairy cow industry.