PMID- 27328025 OWN - NLM STAT- MEDLINE DCOM- 20180716 LR - 20180716 IS - 1448-5990 (Electronic) IS - 1031-3613 (Linking) VI - 29 IP - 7 DP - 2017 Jul TI - Subfertility in androgen-insensitive female mice is rescued by transgenic FSH. PG - 1426-1434 LID - 10.1071/RD16022 [doi] AB - Androgens synergise with FSH in female reproduction but the nature of their interaction in ovarian function and fertility is not clear. In the present study, we investigated this interaction, notably whether higher endogenous FSH can overcome defective androgen actions in androgen receptor (AR)-knockout (ARKO) mice. We generated and investigated the reproductive function of mutant mice exhibiting AR resistance with or without expression of human transgenic FSH (Tg-FSH). On the background of inactivated AR signalling, which alone resulted in irregular oestrous cycles and reduced pups per litter, ovulation rates and antral follicle health, Tg-FSH expression restored follicle health, ovulation rates and litter size to wild-type levels. However, Tg-FSH was only able to partially rectify the abnormal oestrous cycles observed in ARKO females. Hence, elevated endogenous FSH rescued the intraovarian defects, and partially rescued the extraovarian defects due to androgen insensitivity. In addition, the observed increase in litter size in Tg-FSH females was not observed in the presence of AR signalling inactivation. In summary, the findings of the present study reveal that FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility. FAU - Walters, K A AU - Walters KA AD - ANZAC Research Institute, Andrology Laboratory, University of Sydney, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia. FAU - Edwards, M C AU - Edwards MC AD - ANZAC Research Institute, Andrology Laboratory, University of Sydney, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia. FAU - Jimenez, M AU - Jimenez M AD - ANZAC Research Institute, Andrology Laboratory, University of Sydney, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia. FAU - Handelsman, D J AU - Handelsman DJ AD - ANZAC Research Institute, Andrology Laboratory, University of Sydney, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia. FAU - Allan, C M AU - Allan CM AD - ANZAC Research Institute, Andrology Laboratory, University of Sydney, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia. LA - eng PT - Journal Article PL - Australia TA - Reprod Fertil Dev JT - Reproduction, fertility, and development JID - 8907465 RN - 0 (AR protein, mouse) RN - 0 (Follicle Stimulating Hormone, Human) RN - 0 (Receptors, Androgen) RN - 0 (Recombinant Proteins) SB - IM MH - Animals MH - Disease Models, Animal MH - Estrus MH - Female MH - Fertility/genetics/physiology MH - Follicle Stimulating Hormone, Human/*genetics/*physiology MH - Humans MH - Infertility, Female/genetics/physiopathology/*therapy MH - Litter Size MH - Male MH - Mice MH - Mice, Inbred C3H MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Ovary/pathology/physiopathology MH - Pregnancy MH - Receptors, Androgen/*deficiency/genetics MH - Recombinant Proteins/genetics/metabolism EDAT- 2016/06/22 06:00 MHDA- 2018/07/17 06:00 CRDT- 2016/06/22 06:00 PHST- 2016/01/12 00:00 [received] PHST- 2016/05/30 00:00 [accepted] PHST- 2016/06/22 06:00 [pubmed] PHST- 2018/07/17 06:00 [medline] PHST- 2016/06/22 06:00 [entrez] AID - RD16022 [pii] AID - 10.1071/RD16022 [doi] PST - ppublish SO - Reprod Fertil Dev. 2017 Jul;29(7):1426-1434. doi: 10.1071/RD16022.