Voluntary Exercise Improves Estrous Cyclicity in Prenatally Androgenized Female Mice Despite Programming Decreased Voluntary Exercise: Implications for Polycystic Ovary Syndrome (PCOS)

Abstract

Prenatal androgen (PNA) exposure in mice produces a phenotype resembling lean polycystic ovary syndrome. We studied effects of voluntary exercise on metabolic and reproductive parameters in PNA vs vehicle (VEH)-treated mice. Mice (8 wk of age) were housed individually and estrous cycles monitored. At 10 weeks of age, mice were divided into groups (PNA, PNA-run, VEH, VEH-run, n = 8-9/group); those in the running groups received wheels allowing voluntary running. Unexpectedly, PNA mice ran less distance than VEH mice; ovariectomy eliminated this difference. In ovary-intact mice, there was no difference in glucose tolerance, lower limb muscle fiber types, weight, or body composition among groups after 16 weeks of running, although some mitochondrial proteins were mildly up-regulated by exercise in PNA mice. Before running, estrous cycles in PNA mice were disrupted with most days in diestrus. There was no change in cycles during weeks 1-6 of running (10-15 wk of age). In contrast, from weeks 11 to 16 of running, cycles in PNA mice improved with more days in proestrus and estrus and fewer in diestrus. PNA programs reduced voluntary exercise, perhaps mediated in part by ovarian secretions. Exercise without weight loss improved estrous cycles, which if translated could be important for fertility in and counseling of lean women with polycystic ovary syndrome.

Regular and Moderate Exercise Counteracts the Decline of Antioxidant Protection but Not Methylglyoxal‐Dependent Glycative Burden in the Ovary of Reproductively Aging Mice

“…Recently, it has been reported that reproductive dysfunctions in mice with polycystic ovary syndrome (PCOS), an ovarian disease associated with glycative stress [11, 14], can be ameliorated by exercise without weight loss [15]. …”

The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams

“…Many animal models of PCOS represent the lean phenotype of the syndrome with normal or growth restricted fetuses 22 , 32 . The novelty of the present study is that we combine the well characterized PNA mouse model 9 – 11 , 28 with a maternal obesity model 18 . We demonstrate that diet-induced obesity results in enlarged maternal livers accompanied with a marked increase in maternal liver TG content, which was most pronounced in the DHT-treated animals.…”

“…As expected, the serum levels of DHT were higher in mice injected with DHT demonstrating that the dams were hyperandrogenized at the end of pregnancy. No previous studies using the maternal androgen excess model have measured DHT in maternal serum in mice 9 – 11 , 28 . Since maternal androgens have the potential to affect the fetus and/or placental function directly 32 , it is important to investigate the circulating levels of this hormone.…”

“…In fact, high levels of androgens during pregnancy have been related to metabolic 25 and cardiovascular 26 derangements. In animal models, we and others have also shown that prenatally androgenized (PNA) female rat offspring are born small for gestational age (SGA), but normal fetal weight has also been reported 9 – 11 , 22 , 27 , 28 . However, in pregnant women with PCOS, especially those that are obese, both SGA and large for gestational age (LGA) occur 29 , 30 .…”

Sport, doping and female fertility

“…The latter hypothesis could be indirectly supported by the experimental evidence that female rats with PCOS induced by prenatal androgen exposure, show reduced voluntary running. In fact, normal mice voluntarily ran several kilometers per day, while mice with PCOS ran approximately one-third less distance [ 77 ]. The mechanisms underlying reduced running does not seem to be related to decreased exercise capacity but is more likely due to decreased reward from running.…”