Adipose tissue plays an important role in regulating female fertility, owing to not only its energy stores but also the endocrine actions of secreted
adipokines. As one of the
adipokines,
adiponectin is almost exclusively secreted from the fat, and its circulating concentration is paradoxically reduced in
obesity. Although recent studies implied a purported positive role of
adiponectin in ovarian functions, definitive in vivo evidence has been sorely lacking. We have consistently observed
subfertility in female
adiponectin null mice and therefore postulated a protective role of
adiponectin in ovarian functions. Female
adiponectin null mice displayed impaired fertility, reduced retrieval of oocytes, disrupted estrous cycle, elevated number of atretic follicles, and impaired late folliculogenesis. Analysis of their sera revealed a significant decrease in
estradiol and FSH but an increase in LH and
testosterone at proestrus. In addition, we found marked reduction of
progesterone levels at diestrus, a significant decrease in
LH receptor expression as well as in the number of
GnRH immunoreactive neurons.
Adiponectin deficiency also altered the peak concentrations of LH surge and led to lower expression of
Cytochrome P450 family 11 subfamily A member 1 (P450scc), an
enzyme critical for
progesterone synthesis, as well as an increase in BCL2 associated X, apoptosis regulator and
Insulin like growth factor binding protein 4 in atretic follicles. These physiological and molecular events were independent of
insulin sensitivity. Thus, we have revealed a novel mechanism linking
adiponectin and female fertility that entails regulation of reproductive
hormone balance and ovarian follicle development.