Pituitary-specific overexpression of porcine follicle-stimulating hormone leads to improvement of female fecundity in BAC transgenic mice.

Abstract

Follicle-stimulating hormone (FSH) is a pituitary glycoprotein that, together with luteinizing hormone, plays a crucial role in ovarian folliculogenesis and female fertility. We previously found that FSH beta is a major gene controlling high prolificacy of Chinese Erhualian pigs. To directly study the biological effects on reproductive function of porcine FSH (pFSH) for polyovulatory species, we generated a novel gain-of-function mouse model using a bacterial artificial chromosome (BAC) system to jointly introduce 92 kb and 165 kb genomic fragments comprising the pFSH α- and β-subunit genes. These directed the physiological expression of pFSH with the same temporal and spatial pattern as endogenous FSH in female transgenic (TG) mice. Serum levels of biologically active pFSH heterodimers in independent TG lines ranged from 6.36 to 19.83 IU/L. High basal pFSH activity led to a significant reduction of serum LH and testosterone levels in TG females compared to wild-type (WT) littermates, yet endogenous FSH and estradiol levels were significantly elevated. Interestingly, ovarian histology showed that the number of corpora lutea was significantly higher at 14 and 28 weeks of age in TG females and breeding curves revealed that mean litter sizes of TG females were obviously larger than for WT littermates before 52 weeks of age. These findings indicate that pituitary-specific overexpression of pFSH within physiological boundaries can increase ovulation rate and litter size, but it does not cause reproductive defects. Therefore, our TG mouse model provides exciting insights for investigating the actions of pFSH in vivo.