Anna P Ponnampalam

Currently, our understanding of hormonal regulation within the female reproductive system is largely based on our knowledge of estrogen and progesterone signalling. However, while the important functions of androgens in male physiology are well known, it is also recognized that androgens play critical roles in the female reproductive system. Further, androgen signalling is altered in a variety of gynaecological conditions, including endometriosis and polycystic ovary syndrome, indicative of regulatory roles in endometrial and ovarian function. Co-regulatory mechanisms exist between different androgens, estrogens, and progesterone, resulting in a complex network of steroid hormone interactions. Evidence from animal knockout studies, in vitro experiments, and human data indicate that androgen receptor expression is cell-specific and menstrual cycle stage-dependent, with important regulatory roles in the menstrual cycle, endometrial biology, and follicular development in the ovaries. This review will discuss the expression and co-regulatory interactions of androgen receptors, highlighting the complexity of the androgen signalling pathway in the endometrium and ovaries, and the synthesis of androgens from additional alternative pathways previously disregarded as male-specific. Moreover, it will illustrate the challenges faced when studying androgens in female biology, and the need for a more in-depth, integrative view of androgen metabolism and signalling in the female reproductive system.

Fish oil (FO) supplements are consumed during pregnancy to increase dietary omega-3. However, FO is often oxidized past recommended limits. In rats, a large dose of highly oxidized FO substantially increased newborn mortality, but the effects of human-relevant doses of less oxidized oil are unknown. A dose-response study in rats was conducted to estimate the safe level of oxidation during pregnancy. Sprague-Dawley rat dams were mated, then individually housed and provided with a gel treatment on each day of pregnancy. Treatment groups differed only in the FO content of the gel; control (no oil), PV5, PV10, and PV40 [0.05 mL of FO oxidized to a peroxide value (PV) of 5, 10, or 40 meq/kg], or PV40(1 mL) (1 mL of PV40). A subset of dams was culled on gestational day 20 to enable sampling, and the remainder were allowed to give birth. Newborn mortality was recorded. Offspring were sampled on postnatal days 2 and 21, and dams on day 21. There were no signs of unwellness during pregnancy. However, there was markedly increased neonatal mortality affecting the PV40(1 mL) (12.8%) and PV40 (6.3%) groups, but not the control, PV5, or PV10 groups (1%–1.4%). Dietary-oxidized FO altered the expression of placental genes involved in antioxidant pathways and the production of free radicals. Highly oxidized FO was toxic in rat pregnancy leading to a marked increase in mortality even at a human-relevant dose. We observed no toxic effects of FOs with PV ≤10 meq/kg, suggesting that this is an appropriate maximum limit.